Testosterone - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

TESTOSTERONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES ...

Author: ICON Health Publications

65 downloads 864 Views 2MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!
Report copyright / DMCA form

DOWNLOAD PDF

TESTOSTERONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Testosterone: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84091-1 1. Testosterone-Popular works. I. Title.

iii

Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

iv

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on testosterone. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

v

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

vi

About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON TESTOSTERONE ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Testosterone .................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 67 CHAPTER 2. NUTRITION AND TESTOSTERONE .............................................................................. 109 Overview.................................................................................................................................... 109 Finding Nutrition Studies on Testosterone ............................................................................... 109 Federal Resources on Nutrition ................................................................................................. 113 Additional Web Resources ......................................................................................................... 113 CHAPTER 3. ALTERNATIVE MEDICINE AND TESTOSTERONE ....................................................... 115 Overview.................................................................................................................................... 115 National Center for Complementary and Alternative Medicine................................................ 115 Additional Web Resources ......................................................................................................... 124 General References ..................................................................................................................... 129 CHAPTER 4. DISSERTATIONS ON TESTOSTERONE ......................................................................... 131 Overview.................................................................................................................................... 131 Dissertations on Testosterone .................................................................................................... 131 Keeping Current ........................................................................................................................ 133 CHAPTER 5. CLINICAL TRIALS AND TESTOSTERONE .................................................................... 135 Overview.................................................................................................................................... 135 Recent Trials on Testosterone .................................................................................................... 135 Keeping Current on Clinical Trials ........................................................................................... 141 CHAPTER 6. PATENTS ON TESTOSTERONE .................................................................................... 143 Overview.................................................................................................................................... 143 Patents on Testosterone ............................................................................................................. 143 Patent Applications on Testosterone.......................................................................................... 167 Keeping Current ........................................................................................................................ 196 CHAPTER 7. BOOKS ON TESTOSTERONE ........................................................................................ 197 Overview.................................................................................................................................... 197 Book Summaries: Federal Agencies............................................................................................ 197 Book Summaries: Online Booksellers......................................................................................... 198 The National Library of Medicine Book Index ........................................................................... 200 Chapters on Testosterone ........................................................................................................... 201 CHAPTER 8. MULTIMEDIA ON TESTOSTERONE ............................................................................. 203 Overview.................................................................................................................................... 203 Audio Recordings....................................................................................................................... 203 CHAPTER 9. PERIODICALS AND NEWS ON TESTOSTERONE .......................................................... 205 Overview.................................................................................................................................... 205 News Services and Press Releases.............................................................................................. 205 Newsletter Articles .................................................................................................................... 209 Academic Periodicals covering Testosterone.............................................................................. 211 CHAPTER 10. RESEARCHING MEDICATIONS ................................................................................. 213 Overview.................................................................................................................................... 213 U.S. Pharmacopeia..................................................................................................................... 213 Commercial Databases ............................................................................................................... 215 Researching Orphan Drugs ....................................................................................................... 215 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 219 Overview.................................................................................................................................... 219

viii Contents

NIH Guidelines.......................................................................................................................... 219 NIH Databases........................................................................................................................... 221 Other Commercial Databases..................................................................................................... 224 The Genome Project and Testosterone ....................................................................................... 224 APPENDIX B. PATIENT RESOURCES ............................................................................................... 229 Overview.................................................................................................................................... 229 Patient Guideline Sources.......................................................................................................... 229 Finding Associations.................................................................................................................. 231 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 233 Overview.................................................................................................................................... 233 Preparation................................................................................................................................. 233 Finding a Local Medical Library................................................................................................ 233 Medical Libraries in the U.S. and Canada ................................................................................. 233 ONLINE GLOSSARIES................................................................................................................ 239 Online Dictionary Directories ................................................................................................... 240 TESTOSTERONE DICTIONARY .............................................................................................. 241 INDEX .............................................................................................................................................. 333

1

FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with testosterone is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about testosterone, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to testosterone, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on testosterone. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to testosterone, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on testosterone. The Editors

1 From

the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

3

CHAPTER 1. STUDIES ON TESTOSTERONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on testosterone.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and testosterone, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “testosterone” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

The Role of Dihydrotestosterone in Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 2(1): 18-21. February 1992. Summary: The enzyme 5beta-reductase converts intraprostatic testosterone into the potent androgen dihydrotestosterone. This article discusses the role of dihydrotestosterone (DHT) in benign prostatic hyperplasia (BPH). Topics include androgen-dependent growth, the 5beta-reductase deficiency syndrome, development of a drug (finasteride) to inhibit 5beta-reductase production, and the biochemical and clinical efficacy of finasteride. The author focuses on the use of finasteride in early BPH to prevent further progression of the disease. 1 figure. 1 table. 17 references. (AA-M).

4

Testosterone

•

Testosterone Reduces Neuronal Secretion of Alzheimer's Beta-Amyloid Peptides Source: Proceedings of the National Academy of Science. 97(3): 1202-1205. 2000. Summary: This journal article describes a study investigating whether testosterone, a hormone whose levels decrease with age in older men and postmenopausal women, reduces neuronal secretion of beta-amyloid peptides in brain regions susceptible to developing Alzheimer's disease (AD) pathology. Studies have shown that treating cultured neurons with 17 beta-estradiol reduces the secretion of beta-amyloid 40/42 peptides, suggesting that estrogen replacement therapy may protect women against the development of AD by regulating beta-amyloid peptide metabolism. In this study, researchers found that treatment with testosterone decreased the secretion of betaamyloid peptides from N2a cells and rat primary cerebrocortical neurons. The authors conclude that testosterone supplementation in elderly men may be protective against the development of AD; women may benefit from estrogen replacement therapy supplemented with androgens. They advise further investigation into the molecular mechanisms in which steroid hormones regulate beta-amyloid peptide metabolism.

Federally Funded Research on Testosterone The U.S. Government supports a variety of research studies relating to testosterone. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to testosterone. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore testosterone. The following is typical of the type of information found when searching the CRISP database for testosterone: •

Project Title: 5 ALPHA REDUCTASE GENOTYPE, RACE PROSTATE CANCER RISK Principal Investigator & Institution: Reichardt, Juergen K.; Biochem and Molecular Biology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-MAY-2004 Summary: (Adapted from the Investigator's Abstract) Prostate cancer is currently the most common cancer among American men. Regulation of prostatic cell growth is largely controlled by androgens including especially dihydrotestosterone (DHT). This compound is synthesized from the male hormone testosterone by the enzyme 5-alpha reductase which is encoded in the prostate by the SRD5A2 gene. The etiology of prostate

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies

5

cancer appears to include increased steroid 5-alpha reductase activity particularly across racial/ethnic groups which are at very different risk for prostate cancer, such as highrisk African-Americans and lower risk Asians, the two extreme groups for risk. We have identified and characterized genetic variability in the SRD5A2 gene among various racial/ethnic groups in the US and between prostate cancer cases and controls. These investigations made use of a large multiethnic cohort in Los Angeles and Hawaii. We propose to build on and expand our studies of the SRD5A2 gene and prostate cancer by epidemiologic, genetic and biochemical methods. It is our overall hypothesis that genetic variation at the SRD5A2 locus plays a significant role in predisposition to and progression of prostate cancer and in explaining the racial/ethnic variation of risk. To this end, we intend to investigate the following interrelated six specific aims: 1) To identify all constitutional ("germline") DNA variations across the entire SRD5A2 gene that might contribute to predisposition to prostate cancer; 2) To determine the relationship between each variant identified in Specific Aim 1 to prostate cancer risk in for racial/ethnic populations: 4) To identify somatic mutations in the SRD5A2 gene involved in prostate cancer progression; 5) To characterize the biochemical properties of the somatic DNA genetic variants identified in Specific aims 1 and 4 in an in vitro model system; 6) To determine the contribution of somatic DNA genetic variants in the SRD5A2 gene to prostate cancer progression within and across racial/ethnic groups. Therefore, we will investigate the molecular basis of predisposition to prostate cancer and its progression in a multidisciplinary study rooted in molecular epidemiology with significant implications for presymptomatic identification of at-risk individuals, targeted chemoprevention and improved treatment of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A NOVEL NEURAL PATHWAY CONTROLS TESTOSTERONE RELEASE Principal Investigator & Institution: Rivier, Catherine L.; Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-MAY-2004 Summary: We recently uncovered the existence of a neural brain-testicular pathway that interferes with Leydig cell function independently of the pituitary. Specifically, we showed that within 5 min of their intracerebroventricular (icv) injection, corticotropinreleasing factor (CRF) or isoproterenol (ISO) blocked the stimulatory effect of human chorionic gonadotropin (hCG) on testosterone (T) release. Systemic alcohol injected 15 min prior to hCG exerted a similar effect. The ability of icv CRF or ISO, or of alcohol, to block the T response was neither mimicked nor reversed by iv pretreatment with a GnRH antagonist, indicating that their inhibitory effect was not due to low LH levels. In contrast, the icv injection of an adrenergic antagonist partially reversed the effect of icv ISO, icv CRF or systemic alcohol. These results support the existence of a neural pathway that rapidly inhibits Leydig cell function through an adrenergic mechanism. At present, neuromorphological evidence for this pathway is missing. Under Specific Aim 1, we will use a viral transneuronal labeling method to identify sites in the central nervous system (CNS) that are involved in this pathway. This powerful neuroanatomical tool consists of the injection of pseudorabies virus (PRV) into the testis. Following replication, PRV is transported in a retrograde fashion to the perikarya of first-order neurons innervating the gonad, then to second-, third- and fourth-order neurons as the infection proceeds to further synaptically linked cell bodies. Viruslabeled neurons are identified by means of immunocytochemistry using polyclonal antibodies. Specificity of labeling will be determined by the ability of spermatic

6

Testosterone

denervation and/or spinal cord T1 section, to eliminate PRV labeling in higher structures. After we have identified brain areas that belong to the proposed pathway, we will conduct functional experiments to determine its physiological importance. Under Specific Aim 2, we will microinfuse CRF or ISO in selected brain areas. We anticipate that by activating the proposed inhibitory pathway, these treatments will decrease hCG-induced T secretion, compared to results obtained in animals infused with the vehicle. Under Specific Aim 3, we will sever the spinal cord at the T1 level or lesion specific hypothalamic areas thought to be involved in the proposed pathway, to determine whether these procedures block the inhibitory effect of icv CRF or systemic alcohol on hCG-induced T secretion. These experiments will provide the first morphological and functional evidence of the existence of a multisynaptic neural pathway between the testes and the CNS, that is influenced by alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACTIVATION OF SPERMATOGENIC RECOVERY AFTER TOXIC INSULT Principal Investigator & Institution: Meistrich, Marvin L.; Professor; Expermtl Radiation Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2006 Summary: Exposure of men to certain environmental, and medical toxicants results in prolonged azoospermia. Occasionally spermatogenesis recovers, indicating that stem (type A) spermatogonia survived but their differentiation was limited. Testes of irradiated or dibromocholoropropane (DBCP) treated rats contain A spermatogonia that remain for over one year but fail to differentiate, and may be a model for the human situation. In the rat, transient suppression of testosterone results in progression of spermatogenesis and restoration of fertility. The hypothesis is proposed that, in toxicanttreated rats, greater restoration of fertility can be achieved by manipulating various steroid hormones and FSH, which are regulating spermatogonial development by acting on Sertoli cells and possibly another steroid-receptor positive somatic cell of the testis to modulate the expression of specific genes. Initially, irradiation will be used in all the Aims, but the generality of major findings to other toxicants will be checked using DBCP-induced gonadal damage. To determine whether enhanced and prolonged recovery can be achieved, rats will be treated both before and after toxicant exposure with different combinations of a GnRH antagonist, testosterone, estrogens, or progestins. The effects of toxicant dose, timing of hormones, and specific hormone treatment on the duration of recovery will further elucidate inhibitory mechanisms and suggest procedures for restoration of spermatogenesis. To evaluate the roles of different steroid-responsive cells (Sertoli, peritubular, Leydig, vascular), three approaches will be used. These are in vitro culture of tissue fragments, isolated tubules, and tubule components; in vivo elimination of Leydig cells; and determining whether the edema (likely from vascular damage) in toxicant-treated testes correlates with the inhibition of spermatogonial development. Initial steps will be taken to identify genes involved. RNA from purified populations of the target cell from irradiated-only and hormone-treated irradiated rats will be subjected to subtractive hybridization to obtain libraries of differentially expressed clones. This study should define hormones or other factors that might be used as intervention to enhance recovery of fertility in men following certain types of toxicant exposure, cancer of immunosuppressive therapy, aging, and idiopathic infertility that result in blocks in germ cell development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

7

Project Title: AGE,GENDER, SEROTONIN AND RESPIRATORY CONTROL Principal Investigator & Institution: Behan, Mary; Professor; Comparative Biosciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Serotonin (5HT) plays a major role in breathing and the control of upper airway function. The proposed research will test the hypothesis that, with increasing age, there is a gender- specific decrease in serotonergic modulation of respiratory motoneurons. Because of gender-related differences, aging males may be uniquely susceptible to breathing disorders such as obstructive sleep apnea. Our preliminary data indicate that 5HT immunoreactivity in the hypoglossal nucleus decreases with age in male rats, but increases with age in female rats. Furthermore, long term facilitation, a 5HT-dependent increase in respiratory motor output following intermittent hypoxia, decreases to older male rats, but increases to older female rats. This is the first description of age-associated change in serotonergic modulation of respiratory control, and the first description of sexual dimorphism in age-related changes in any aspect of the serotonergic nervous system. The proposed research will test the hypothesis that gonadal hormones have a neuroprotective role in the maintenance of serotonergic modulation of respiratory motoneurons in female rats with increasing age, and can potentially reverse or delay the age-associated changes that occur in male rats. Five specific aims are proposed, each corresponding to a testable hypothesis. First, we will use neurochemical and anatomical assays to detect age- and gender- related changes in key elements of the serotonergic neuromodulatory system (5HT, 5HT receptors, and the serotonin reuptake transport protein) in hypoglossal and phrenic motor nuclei. Secondly, we propose to determine if there are functional consequences of aging and gender on respiratory responses to hypoxia in awake rats. Thirdly, we will test the hypothesis that serotonin-dependent components of the hypoxic ventilatory response are decreased selectively with aging in male rats. Finally, we propose to investigate the influence of neutering and hormone replacement therapy (estrogen, progesterone, testosterone) on our anatomical and physiological indices of serotonergic modulation of respiration in male and female rats. To our knowledge, this is the first proposal to study age and gender effects on any form of plasticity in respiratory control. An understanding of these mechanisms may lead to therapeutic strategies for intervention in age-related breathing disorders that affect both men and women such as obstructive sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ALLIUM COMPOUNDS IN CONTROL OF HUMAN PROSTATE CANCER Principal Investigator & Institution: Pinto, John T.; Institute for Cancer Prevention 1 Dana Rd Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by the applicant) This exploratory grant seeks to establish a novel role for allium derivatives from garlic in control of human prosta cancer by acting as anti-androgens. Our preliminary observations reveal that when androgen-responsive human prostate cancer cells (LNCaP) are incubated with allium derivatives in vitro, two events take place: (a) the proliferation rate of the LNCaP cells is markedly reduced and (b) testosterone concentration rapidly decreases in both the media in which the cells are growing as well as in the cells themselves. Furthermore, when testosterone is added back to the media of LNCaP cells previously exposed to allium derivatives, the decrease

8

Testosterone

in initial rate of cell proliferation is only partially restored. These preliminary results strongly suggest that allium-induced inhibition of cell proliferation and accelerated removal of testosterone are linked. We hypothesize that allium derivatives increase testosterone disappearance by accelerating conversion to inactive metabolites thereby diminishing the action of testosterone on the prostate. To test I validity of this hypothesis, we shall measure the conversion rate of testosterone to dihydrotestosterone (DHT), a more potent metabolite, through 5-alpha reductase, and the formation rate of a series of inactive testosterone metabolites, a determined by GC-MS methods. Concurrent with these experiments, we shall determine the mechanism of inhibition of growth of human prostat cancer cells by allium derivatives, whether by apoptosis or cytostasis. We shall determine where in the cell cycle growth inhibition occurs, whether or not apoptosis is induced, and whether changes in specific signal transduction proteins occ in later experiments, we shall examine effects of allium derivatives on regulatory proteins most likely to be relevant unc these conditions in modifying cell cycle transcription (i.e., cyclin B, cdk 2). These studies will then be extended in the second year to examine effects of allium derivatives on human prostate cancer cells (LNCaP C4-2) that exhibit androgen receptors but are non-responsive to its trophic effects. Together, the LNCaP and LNCaP C4-2 cell lines should serve as appropriate models, respectively, for early prostate cancer that is androgen-sensitive and later prostate cancer that is largely unresponsive to androgen manipulations. These studies should provide a creative approach to prevention and control of prostate cancer that is feasible and cosi effective, and should lead to an innovative advance in correlating certain dietary modifications and prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF SEX HORMONES AND LIPOPROTEINS IN YOUNG MALES Principal Investigator & Institution: Barton, Bruce A.; Senior Statistician and Vice President; Maryland Medical Research Institute, Inc 600 Wyndhurst Ave Baltimore, Md 21210 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Provided by Applicant) This application requests support for secondary analysis of the Sex Hormones and Lipoproteins in Adolescent Males Study (HD/HL18281), a 3-year (1984-1987) study of lipids, blood pressure, weight, fat patterning, and sex steroid hormones (SSH) in adolescent males. A total of 664 black and white males, ages 10-15, were enrolled into a study designed as a series of repeated data collections over 2 years within age cohorts. Cross-sectional analyses have been used to explain differences during adolescence in SSH and SSH-lipid relationships between black and white boys and between boys with and without a family history of CHD. When the data were originally collected for this study, theoretical models of flexible longitudinal analytic techniques had been developed, but were not available for computer use. These techniques, now supported by software, allow a more powerful and complete analysis of these data. The primary aim of these analyses is to explicate the contribution of changes in SSH and fat patterning to changes in plasma concentrations of high (HDL-C) and low (LDL-C) density lipoprotein cholesterol, triglycerides (TG), and apolipoproteins (apo) Al, All, and B occurring during puberty in males. SSH assayed included estradiol (E2) and free testosterone (T). We will test the following hypotheses: (1) increasing free T predicts/leads to decreases in HDL-C and increases in LDL-C, apo B, and the LDL-C/HDL-C ratio in adolescent males; (2) increasing E2 predicts decreases in apo B, LDL-C and the LDL-C/HDL- C ratio, but the

Studies

9

resultant effects will vary with adiposity and fat patterning; (3) rapid weight gain predicts increased central adiposity, defined as the ratio of truncal skinfolds to total skinfolds, and with greater decreases in HDL-C and increases in triglycerides, apo B, LDL-C and the LDL- C/HDL-C ratio. Rapid weight gain predicts increased E2, but the atherogenic effects of increased central adiposity on lipids are greater than the antiatherogenic effects of E2. These analyses will provide a better understanding of metabolic factors underlying obesity-hormone-lipoprotein relationships. Given the welldocumented increase in obesity in American youth, these analyses are especially pertinent and address important public health issues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANDROGENS, MYOSTATIN, AND SARCOPENIA IN OLDER WOMEN Principal Investigator & Institution: Cappola, Anne R.; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-DEC-2002 Summary: (provided by applicant): Dr. Anne Cappola, who trained in Endocrinology at the Massachusetts General Hospital and the Johns Hopkins Hospital, recently completed an Sc.M. in Epidemiology at the Johns Hopkins School of Public Health and a fellowship at the Johns Hopkins Center on Aging and Health. In April, 2001, Dr. Cappola joined the faculty at the University of Maryland as Assistant Professor of Medicine and Epidemiology. She has strong mentor ship from Dr. Alan Shuldiner, an endocrinologist with expertise in aging, and Dr. Linda Fried, a geriatrician and epidemiologist renowned for her work on frailty. They will provide her with extensive resources and a stimulating interdisciplinary environment to launch her independent academic career. Sarcopenia, the involuntary loss of skeletal muscle mass and function, is a potentially modifiable condition that contributes to frailty, functional dependence, and falls in older individuals. The role of the endocrine system in the development of sarcopenia is poorly understood. The central goal of this proposal is to define the role of androgens and myostatin in sarcopenia in older women through examination of epidemiologic and molecular data. In Specific Aim 1, Dr. Cappola proposes to characterize the distribution of ovarian and adrenal androgens and myostatin in a random sample of women over the age of 65 using banked blood from the Cardiovascular Health Study (CHS). In Specific Aim 2, she will perform analyses to determine whether lower or declining levels of androgens and/or higher or increasing levels of myostatin are independently associated with sarcopenia in CHS and in a cohort of women with relatively high function, the Women?s Health and Aging Study II. In Specific Aim 3, she will perform a pilot study of low-dose testosterone in androgendeficient older women to evaluate the safety and efficacy of this intervention and to delineate the molecular mechanisms whereby androgens mediate changes in muscle using functional genomics approaches. Dr. Cappola?s interdisciplinary training, strong mentor ship, carefully designed career development program, supportive environment, and novel research plan will give her the experience and tools she needs to develop into a highly successful, independent clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ANGIOGENIC DETERMINANTS OF ENDOGENOUS ADULT NEUROGENESIS Principal Investigator & Institution: Goldman, Steven A.; Professor; Neurology and Neuroscience; Weill Medical College of Cornell Univ New York, Ny 10021

10

Testosterone

Timing: Fiscal Year 2002; Project Start 01-AUG-1992; Project End 31-MAR-2006 Summary: (provided by applicant): The vocal control nucleus HVC of adult songbirds generates new neurons throughout life from nearby ventricular zone progenitor cells. The recruitment and survival of these neurons is modulated by the gonadal steroids testosterone and estradiol. Yet endothelial cell division is the first cellular response noted in the adult HVC after testosterone administration, and precedes androgenassociated gliogenesis and neuronal recruitment by over a week. We have found that testosterone rapidly induces the production of both vascular endothelial growth factor (VEGF) and its receptor VEGF-R2/KDR in HVC. This leads to endothelial division, which anticipates the regionally-restricted expansion of the HVC microvasculature. The activated endothelial cells then produce the neurotrophin BDNF, which has been shown to support neuronal recruitment from the mammalian as well as the avian ventricular zone, and whose induction is associated with the recruitment of new neurons to HVC. Gonadal steroid-induced endothelial and matrix-released cytokines may thereby contribute importantly to neuronal recruitment in the adult brain. In this competitive renewal application, we postulate that gonadal steroid-induced angiogenesis may be critical to neuronal addition to the adult HVC, and that angiogenesis may provide necessary permissive conditions for neuronal recruitment into adult brain parenchyma. To better understand the permissive conditions for the integration of new neurons into adult brain, we propose to ask the following: 1) Is the gonadal steroid-associated induction of VEGF and its receptor necessary for testosterone-induced angiogenesis in the adult HVC? 2) Is steroid-induced angiogenesis necessary for testosterone-mediated neuronal recruitment? Does the suppression of angiogenesis abrogate neuronal addition to HVC? 3) Is local angiogenesis sufficient to direct neuronal recruitment from a neurogenic epithelium? Do new neurons migrate selectively to HVC because of its high BDNF levels after gonadal steroid activation? 4) Do steroid-activated matrix metalloproteinases contribute importantly to neuronal addition? Does MMP inhibition suppress recruitment? These experiments ask if neurogenesis in the adult HVC depends upon antecedent local angiogenesis. They seek to define those necessary and sufficient conditions for neuronal recruitment that may be provided by steroid-activated endothelial cells. By so doing, they extend our understanding of the permissive conditions for neurogenesis in the adult brain, and may inform us as to how to induce neuronal recruitment to, and acceptance by, otherwise non-neurogenic regions of the adult brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AROMATASE INHIBITOR METHYL TESTOSTERONE AND TESTOSTERONE INDUCED BONE SPARING Principal Investigator & Institution: Naftolin, Frederick; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Osteoporosis is a common disease in postmenopausal women and aging men resulting in considerably morbidity and mortality. While estrogen is a recognized bonesparing agent, reports on the effect of testosterone (T) on bone mass are controversial and variable. T's variable action on bones could be due to the requirement of aromatization of T to estrogen, followed by action on bone cell estrogen receptors: This laboratory was first to report the presence of immunoreactive aromatase in osteoblasts in culture. 17alpha-methyl testosterone (MT) is a synthetic steroidal androgen with low affinity for the androgen receptor. It is widely used in hormone replacement therapy in women. MT is also a powerful aromatase (estrogen synthetase) inhibitor that may block

Studies

11

local estrogen formation. We have shown that MT inhibits both aromatization of androstenedione and T-induced proliferation of breast cancer cells by inhibiting aromatase. We propose to use a similar preclinical experimental approach to assess the mechanism of action of T on rat bone mass: We will test the effect of T alone and of T plus MT on bone maintenance in ovariectomized female rats. If MT blocks T's bone maintenance, this will indicate that T's action is indirect, via aromatization, and justify clinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BENEFITS OF TESTOSTERONE ON STRENGTH IN ELDERLY MEN Principal Investigator & Institution: Katznelson, Laurence; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): In this proposal, the effects of testosterone administration alone, or, in combination with exercise, on muscle function in elderly, sedentary men with testosterone deficiency will be investigated. Aging is associated with skeletal muscle sarcopenia and diminished muscle performance, which lead to significant disability from falls and loss of independence. One factor that may lead to sarcopenia is the presence of testosterone deficiency. Serum testosterone levels decrease progressively with age and the majority of elderly men have serum testosterone and free-testosterone levels below the mean for young men. Because testosterone deficiency may lead to alterations in body composition that include decreases in lean mass and strength, it is hypothesized that administration of testosterone therapy to older men with testosterone deficiency (relative to young men) may lead to improvements in muscle function and overall performance. In this proposal, 96 physically inactive elderly men with relative testosterone deficiency will be randomized in a double blind, placebo controlled fashion to receive testosterone enanthate therapy as intramuscular injections at a dose of 200 mg given every 2 weeks versus placebo for a total of 12 weeks. This study will test the hypothesis that administration of gonadal steroids will have a beneficial effect on lean muscle mass, muscle strength, and overall function. These men will be randomized further either to maintain the same level of physical inactivity or to undergo a graded resistance exercise program. This part of the protocol will test the hypothesis that the combined modalities of testosterone and exercise will have additive beneficial effects on muscle mass and function. The goal of these studies will be to determine the efficacy and safety of testosterone administration and, additionally, a home-based exercise program on muscle function in older men with relative testosterone insufficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: BREAST CANCER RISK Principal Investigator & Institution: Terry, Mary B.; Assistant Professor; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Numerous studies have shown associations between markers of fetal growth and important domains of adult health. In particular, several recent studies suggest that high birthweight may be associated with an increased risk of breast cancer later in life. The existing literature on birthweight and breast cancer risk, while intriguing, falls short by its inability to address the following: (1) potential confounding by family factors (e.g. socioeconomic status); (2) the importance of and

12

Testosterone

possible interaction with other measures of fetal growth; (3) the independent effect of maternal characteristics and exposures; (4) potential biological mechanisms; (5) the contribution of postnatal growth: and (6) mediation by adult risk factors. We will address these limitations by use of a novel study design examining the association of early life factors with mammographic density, a strong predictor of future breast cancer risk. Specifically, we will recruit a sibling sample of 500 female pairs (comprising 149 low birthweight (=4000g) females and the other of 178 preeclampsia exposed females. In the combined sibling and single child samples, 15% of the females will have been exposed to their mother?s preeclampsia during pregnancy. All females are offspring of pregnant women enrolled during 1959 to 1967 in two New England sites (Boston and Providence) of the National Collaborative Perinatal Project (NCPP) and in the Childhood Health and Development Study (CHDS). The sibling design will allow us to control for family effects such as socioeconomic status that may influence both birthweight and adult risk factor patterns. Exposure information will be derived from prospectively collected pre and postnatal data on mothers, infants, and childhood growth. Maternal sera collected during the third trimester will be used to measure estrogen (E1, E2, E3), and testosterone. Along with the mammogram, we will also collect adult risk factor data through interview and laboratory assays (including measures of IGF-I, IGFBP-3, androstenedione, testosterone. and SHBG). We hypothesize that high birthweight, high placental weight, high placental/birth weight ratio, high maternal pregnancy weight gain, and high maternal estrogen levels will increase mammographic density in the daughters, and that maternal preeclampsia and higher levels of maternal testosterone will decrease mammographic density in the daughters. We will further examine whether any of these associations are mediated by childhood growth patterns and adult risk factors. This study will advance the literature on early determinants of breast cancer risk by directly addressing tinny of the limitations in the existing literature, allowing a more thorough inspection into what may shape early breast cancer susceptibility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COCAINE & STEROIDS: BRAIN VASCULAR & BEHAVIORAL EFFECTS Principal Investigator & Institution: Kaufman, Marc J.; Assistant Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Chronic cocaine use causes brain abnormalities and cognitive dysfunction, which may both impair a drug user's ability to resist further drug use and decrease the efficacy of treatment interventions. The severity of cocaine associated brain dysfunction is less in women than in men. Further, cocaine abuse treatment appears to benefit women more than men. These sex differences have important therapeutic implications, because they suggest a protective role for estrogen. Thus, estrogen (or a related compound) might be of therapeutic use to protect against brain vascular dysfunction. Cocaine's ability to reduce cerebral blood flow is likely to play a critical role in the development of brain dysfunction. Estrogen has been shown to acutely improve, while progesterone and testosterone acutely degrade vascular function. Consequently, vascular effects of hormones may account for sex differences in cocaine's brain effects. We seek to determine whether estrogen, progesterone, and testosterone alter cocaine pharmacokinetics and cocaine's acute cerebral vasoconstrictive effects. We will measure cocaine and hormone pharmacokinetics, and characterize cardiovascular responses after combined intravenous cocaine (0.4 mg/kg)

Studies

13

and estrogen (men), or progesterone or testosterone (women) treatments. Subsequently, we will evaluate whether these hormones alter cocaine's acute cerebrovascular effects, using a noninvasive functional MRI technique called Dynamic Susceptibility Contrast MRI (DSC MRI). DSC MRI measures cerebral blood volume (CBV) and blood flow (CBF). Study subjects will include healthy men and women with histories of occasional cocaine use, who will each participate in a randomized, placebo-controlled, doubleblind study. The pharmaceutical industry is actively developing novel steroid receptor agents with greater receptor selectivity than the natural hormones, which may improve the ability to selectively modulate vascular responses to cocaine. Thus, if our hypotheses regarding hormonal effects on cocaine-induced vasoconstriction are validated, the potential for identifying effective therapeutics for investigation in chronic treatment trials will be enhanced. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COCAINE ABUSE AND THE ROLE OF GONADAL STEROID HORMONES Principal Investigator & Institution: Mello, Nancy K.; Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): This is a new application (R01) to examine the contribution of gonadal steroid hormones to the abuse related effects of cocaine in preclinical models. Several lines of evidence suggest that gonadal steroid hormones may be important modulators of cocaine's behavioral effects. High levels of estradiol at estrus appear to enhance cocaine's locomotor and reinforcing effects in rats. Gender differences in cocaine's behavioral and biologic effects appear to be mediated by gonadal steroid hormones in both clinical and preclinical studies. Behavioral studies are proposed to determine if gonadal steroid hormones share discriminative stimulus effects and reinforcing effects with cocaine, and if acute or chronic administration of gonadal steroid hormones alters cocaine self-administration and discrimination dose-effect curves. Endocrine studies have shown that intravenous cocaine administration stimulates rapid increases in estradiol and testosterone. Moreover, both estradiol and testosterone have mood enhancing effects in humans. We propose to evaluate the effects of acute or chronic administration of gonadal steroid hormones on cocaine selfadministration and discrimination. In addition, we propose to examine the possible reinforcing and discriminative stimulus effects of these gonadal steroid hormones alone. Both males and females will be studied to determine if there are significant gender differences in behavioral responsivity to cocaine alone and after acute or chronic gonadal steroid treatments. Males and females will be studied in an own-control design across gonadal steroid treatment conditions, and before and after ovariectomy and castration. In normally cycling females, the influence of changing steroid hormone levels across the menstrual cycle will be examined. In ovariectomized females, systematic hormone replacement studies will be conducted to evaluate hormonal effects on cocaine's reinforcing and discriminative stimulus effects. Males will be trained under the same conditions and cocaine dose-effect curves will be determined at the same intervals to permit meaningful gender comparisons. The rapid increases in estradiol and testosterone after i.v. cocaine suggests that any concurrent behavioral effects may be mediated by non-genomic mechanisms. Accordingly, we propose to study the influence of both genomic and non-genomic effects of steroid hormones on cocaine selfadministration and cocaine discrimination. Radioimmunoassay of steroid hormone levels will permit assessment of temporal relationships between hormone levels and

14

Testosterone

cocaine-related behaviors. Data obtained will help to clarify the neurobiologic substrates of cocaine abuse and may have heuristic implications for the development of new strategies for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYP3A FUNCTION IN AGING AFRICANAMERICANS Principal Investigator & Institution: Greenblatt, David J.; Professor and Chair; Pharmacol & Exper Therapeutics; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The Cytochrome P450-3A (CYP3A) drugmetabolizing enzymes are responsible for the biotransformation and clearance of a large number of drugs used in contemporary clinical therapeutics. Individual variation in the expression and activity of CYP3A, both in the liver and gastrointestinal (GI) tract mucosa, appears to underlie much of the large individual variability in pharmacokinetics and response to therapeutically-administered medications that are CYP3A substrates. Many clinical studies demonstrate that age, gender, and ethnicity (race) may account for components of this variation in predictable ways. For example, some data suggest that clearance of certain CYP3A drugs: a Becomes reduced in old age; b Is higher in women than in men; c Is greater in African-Americans than in Caucasians. However the available data are not by any means consistent. Furthermore, variants in the CYP3A4, CYP3A5, and Pregnane-X receptor genes may modulate age-, gender-, or ethnicity-related variations in CYP3A function in ways that are not understood. This study will prospectively evaluate cohorts of young (18-45 years), "young" elderly (60-69 years) and "old" elderly (>70 years) volunteers, consisting of African-American and Caucasian men and women. The study paradigm will assess: a. Hepatic blood flow (HBF), based on clearance of low-dose intravenous lidocaine; b Pharmacokinetics and pharrnacodynamics of intravenous and oral midazolam, a "pure" CYP3A substrate; c The prevalence of variants in the CYP3A4, CYP3A5, and pregnane-X receptor genes, using molecular genetic techniques; d. Plasma concentrations of biologically active testosterone. From a. and b., it is possible to estimate midazolam clearance by both routes, net oral bioavailability, and bioavailability attributable to hepatic and gastrointestinal presystemic extraction. With appropriate statistical techniques, the contributions of age, gender, and ethnicity to overall variance can be determined, as well as modulation of the relationships by genetic CYP3A variants and by biologically active testosterone. This study should provide important mechanistic information on the role of age, gender, and ethnicity as sources of variability in CYP3A-mediated drug metabolism and response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CYTOCHROME P450-ENDOGENOUS SUBSTRATE METABOLISM Principal Investigator & Institution: Waxman, David J.; Professor of Cell and Molecular Biology; Biology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-APR-1999; Project End 31-JAN-2008 Summary: (provided by applicant): The long-range goal of this project is to elucidate the biochemistry and regulation of hepatic cytochrome P450 (CYP) enzymes that catalyze oxidative metabolism of steroid hormones, drugs, carcinogens and other lipophilic substrates of medical or environmental importance. The proposed project period uses the rat as a model system and focuses on pituitary control of sex-specific steroid

Studies

15

hydroxylase P450 enzymes. Special emphasis is placed on the cellular and molecular mechanisms by which plasma growth hormone (GH) and its sex-dependent ultradian secretory patterns regulate the expression of sex-specific steroid hydroxylase P450s in rat liver. The rat liver P450 enzymes CYP2C11 (a testosterone 2alpha- and 16alphahydroxylase) and CYP2A2 (a testosterone 15alpha-hydroxylase) will be studied as prototypic examples of distinct classes of male-specific, GH pattern-regulated liver P450 genes. The proposed studies will test the hypothesis that the sex-dependent expression of liver P450 enzymes involves the cooperative interaction of hepatocyte-enriched nuclear transcription factors (HNFs) with signal transducer and activator of transcription STAT5b, a transcription factor that is strongly activated by the pulsatile GH pattern specifically found in adult male rats. The major objectives of the proposed project are: (1) to elucidate the mechanisms whereby GH-responsive HNFs cooperate with STAT5b to regulate the male-specific liver CYPs 2C 11 and 2A2; (2) to investigate the mechanisms by which GH regulates liver transcription factors, with a focus on novel post-transcriptional regulatory paradigms involving HNF3Beta and HNF4, both of which contribute to the transcriptional regulation of the GH-responsive, male-specific liver CYPs; (3) to employ global liver mRNA expression profiling to identify novel sexually dimorphic GH target genes, including genes that may contribute to the unique response of liver CYPs to the sex-dependent temporal patterns of plasma GH stimulation; and (4) to utilize comparative proteomic methods to identify rat liver nuclear proteins whose abundance or state of post-translational modification is regulated by the sex-dependent plasma GH profile, and which may contribute to GH regulation of liver CYP gene expression. These studies will help elucidate the key cellular and molecular mechanisms whereby GH and its sexually dimorphic plasma profiles regulate the expression of cytochrome P450, an important family of enzymes that controls metabolic processes having a major impact on liver physiology and human health, including steroid hormone metabolism, cholesterol degradation, drug biotransformation and carcinogen activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIAGNOSTIC CENTER Principal Investigator & Institution: Lucia, M S.; Pathology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2004 Summary: This competing renewal application (Diagnostic Center) is for a UO1 grant in response to RFA DK94-18. The investigators describe the widespread economic and medical problems associated with benign prostatic hyperplasia. The overall goal of the study is to test the effectiveness of pharmacological intervention in benign prostatic hyperplasia (BPH) with the hope that pharmacological intervention may prove to be superior to surgery for some patients. The goal of the project under consideration from the University of Colorado is to establish the requested Diagnostic Center for the fullscale trial. The Diagnostic Center will perform assays on peripheral blood with materials sent from several clinical centers; these assays will include prostate specific antigen, luteinizing hormone, testosterone, and dihydrotestosterone. Blood chemistries will be carried out initially and annually for the duration of the trial (described in Appendix F of the protocol). The Diagnostic Center will receive four fixed and two frozen, 18-gauge needle biopsies from each patient entered into the study. A series of slides made from the paraffin-embedded fixed needle biopsies and from the frozen needle biopsies will be examined. These slides will be examined for diagnostic purposes by the principal investigator and an unidentified fellow who will be appointed in the second year of

16

Testosterone

support. Sets of slides will also be made available to the departments of pathology from the hospitals from which the biopsies are obtained. The pathology analyzed in the Diagnostic Center in Denver will be recorded on a standard form that is displayed in the material sent with the application. Additional sections of paraffin-embedded needle biopsies and the remaining materials from frozen needle biopsies will be stored for research in the future. Biopsies will be carried out at the beginning of the study, after one year, and at the end of the study. In addition to the above, immunohistochemical studies will be carried out to assess the expression of prostate specific antigen and the MIB-1 nuclear proliferation antigen. Apoptosis will be evaluated with the TUNEL immunohistochemical technique. Morphometric evaluations will be carried out "using a semiautomated image analysis approach such as that described by Shapiro et al (44)." The step by step methods of staining are listed. The investigators state that conditions stipulated in the pilot study that was carried out in their center made in "impossible.to have any information about the expected ranges of variation for each of the variables with respect to any measures of treatment outcome.From the published literature, however, it is expected that data on 280 patients will be sufficient to produce meaningful results." They state that a ".subset of approximately 280 cases will have detailed analyses performed." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIET AND GENETIC INTERACTIONS IN PROSTATE CANCER Principal Investigator & Institution: Giovannucci, Edward L.; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: Polymorphisms in the CAG repeat length in the AR gene have been demonstrated to correlate with risk of prostate cancer. Using blood samples collected in 1993-94 from 18,000 men in the ongoing HPFS, in combination with buccal brushings to be acquired from an additional 20,000 cohort members, there are plans to characterize risk of prostate cancer, based on CAG polymorphisms in the AR gene. Then, using a nested case-control design of approximately 1,000 projected cases from 1993-2000, the impact of specific nutritional factors on prostate cancer risk will be examined, stratifying across genetic risk. Specifically, associations of diet and nutritional status (pre-adult adiposity and attained height) will be examined with incidence of prostate cancer among men stratified by risk according to number of CAG repeats in the AR gene. Then, an assessment will be made of whether men at higher risk can potentially reduce their excess risk by decreasing their consumption of animal fat and by increasing lycopene and fiber intake, aspects of diet that have already been associated with reduced risk in the overall cohort. Non-nutritional factors that are hypothesized to influence testosterone levels will also be examined, in particular physical activity and smoking, in relation to incidence of prostate cancer among men, stratified by genetic risk according to AR characteristics. A final Aim is to acquire buccal smears for DNA analyses from HPFS participants who did not previously provide blood specimens. This will complete the establishment of a large database consisting of a) updated dietary and other exposure information over a 15 year period for 50,000 men, b) stored DNA samples (blood or buccal brushing) from approximately 38,000 of these men, c) stored plasma from 18,000 participants, and d) archived tissue from incident prostate cancers. The buccal brushings, along with providing the basis for the specific aims in this application, will allow for the rapid testing of future specific hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

17

Project Title: DIFFERENTIAL EFFECTS OF GONADAL STEROIDS ON BONE Principal Investigator & Institution: Leder, Benjamin Z.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: Osteoporosis in men is an important cause of morbidity and mortality, especially in the elderly. Hypogonadism is a well described risk factor for osteoporosis in men, but the mechanisms underlying hypogonadism-induced bone loss are incompletely understood. A fundamental unresolved question in this area concerns the differential effects of androgens and estrogens on the male skeleton. To address this question, in the first of 3 proposed studies, normal men will be randomly assigned to receive: 1) a GnRH analog alone for 12 weeks (suppressing endogenous gonadal steroids to pre-pubertal levels), 2) a GnRH analog plus testosterone (T) (normalizing circulating T and estradiol levels), or 3) a GnRH analog plus T plus an aromatase inhibitor (normalizing T but causing selective estrogen deficiency). Bone turnover markers will be measured every 4 weeks. Bone turnover will increase in Group 1 and should remain unchanged in Group 2. If estrogens are required to maintain normal bone turnover in men, bone turnover should also increase in Group 3. In the second study, normal men will be randomized into similar treatment groups for 8 weeks with the addition of a group that will receive a GnRH analog plus physiologic estradiol. PTH infusions will be performed every 4 weeks and bone turnover markers will be measured every 6 hours during each infusion. By comparing the rates of change in these markers during PTH infusion, the selective effects of androgens and estrogens on the skeletal sensitivity to PTH will be assessed. In the third protocol, murine stromal cell lines and primary mouse osteoblasts will be exposed to estrogens and androgens to assess their differential effects on osteoprotegerin (OPG) and osteoprotegerin-ligand (OPG-L) mRNA expression. These studies will help elucidate the mechanisms by which gonadal steroids act on bone and enable the candidate to appreciate basic developments in bone biology as well as develop and perform future translational research projects. The training portion of the proposal includes regular mentoring with Drs. Finkelstein and Bringhurst, extensive interaction with the Endocrine Unit faculty, and meetings with the GCRC biostatistician. The candidate will also enroll in the Harvard School of Public Health's Clinical Effectiveness Program and participate in courses offered by the MGH Clinical Research Program. These combined research and didactic endeavors will prepare the candidate to achieve his long-term goal to develop an independent research program focusing on the role of gonadal steroids in bone metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DRUG ADOLESCENCE

ABUSE

PUBERTAL

HORMONES

AND

ADHD

IN

Principal Investigator & Institution: Martin, Catherine A.; Psychiatry; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Applicant's Abstract) Mentored Clinical Scientist Development Award: The nominee, Catherine A. Martin, M.D., proposes to develop as an independent clinical researcher in the University of Kentucky Department of Psychiatry and the Center on Drug and Alcohol Research. Her research focus and the purpose of this study is to determine if drug use risk in adolescents with impulse disorders; e.g. Attention Deficit Hyperactivity Disorder (ADHD) and co-morbid Conduct Disorder (CD), is altered by pubertal hormonal changes. Measures of impulsivity, drug use and testosterone in

18

Testosterone

males and testosterone and estradiol in females, will be obtained from 120 subjects at pre-, early and mid-adolescence, (ages 11 l/2 -12 1/2; 13-14; and 14 l/2 -15 1/'2). The overall hypothesis is that testosterone and estradiol increase impulsivity in an already at risk population. This increased impulsivity escalates risk for drug use. Ultimately, the long range goal of this study is to add to the knowledge base and the understanding of how pubertal hormonal changes in impulsive adolescents are related to risk for drug use. The nominee is an established clinician and medical educator with an ongoing investment, but no formal training in research. This award will allow the nominee to acquire the knowledge and experience to develop research paradigms involving at risk psychiatric populotions, particularly those with impulse disorders, and drug use. The nominee will use these skills to develop a drug research program on the course of drug use in children and adolescents with impulse disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF ANDROGEN REPLACEMENT ON BONE METABOLISM Principal Investigator & Institution: Khosla, Sundeep; Professor and Research Chair; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2002 Summary: Osteoporosis is one of the most important public health problems facing aging Americans. Although osteoporosis is more common in women, men also incur substantial bone loss with aging and elderly men have age-specific hip fracture rates and a prevalence of vertebral fractures that are at least half those in women. Estrogen deficiency has clearly been identified as a major risk factor for osteoporosis in women, and the effects of estrogen on the skeleton have been the subject of intensive investigation in recent years. In contrast, data on androgen effects on the skeleton are relatively sparse at present. Nonetheless, since aging is also associated with significant declines in both gonadal and adrenal androgen levels, there is increasing media coverage and popular belief that testosterone or dehydroepiandrosterone (DHEA) therapy can prevent or reverse a number of age-relate changes, including the deterioration in muscle and bone mass, as well as some of the age-related changes in glucose and fat metabolism. In this project, our overall objective is to determine the effects on bone and calcium metabolism of androgen treatment of elderly men and women and to understand better the mechanisms of these effects. We will pursue this objective within the framework of 3 specific aims. Specific Aim 1 is to determine the effects on bone mineral density of two years of testosterone treatment in elderly men and DHEA treatment in elderly men and women. Specific Aim 2 is to assess the short term (6 months) and long term (24 months) effects of androgen therapy on biochemical markers of bone turnover. Specific Aim 3 is to determine the effects of androgen therapy on extra-skeletal calcium metabolism, namely intestinal calcium absorption and renal calcium handling. The studies in this project should,therefore, help define better the potential utility of androgens in the prevention and possible treatment of age-related bone loss. These studies, combined with the proposed studies on androgen effects on muscle (Project 1), insulin sensitivity (Project 3), and fat metabolism and body composition (Project 4), should also provide a much better understanding of the overall benefits and risks of androgen treatment in elderly individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: EFFECT OF ANDROGEN REPLACEMENT ON FAT METABOLISM Principal Investigator & Institution: Jensen, Michael D.; Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905

Studies

19

Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2002 Summary: Aging is associated with increased body fatness, particularly in the trunk. This change in body fat and body fat distribution correlates with insulin resistance, hypertension, dyslipidemia and diabetes mellitus. Reduced levels of circulating androgens in aging men are associated with insulin resistance and centralization of body fat, whereas reduced levels of DHEA are associated with an upper body fat distribution in both aging men and women. If physiologic replacement of reduced levels of testosterone (men) or DHEA (men and women) can reverse some of the aging related changes in body fat distribution and fatty acid metabolism, this could provide a means of improving health as the United States population continues to age. The present experiments will assess whether reversing the age-related decline in androgens and DHEA can have positive effects on body fat distribution and fatty acid metabolism in the elderly. To accomplish these goals, the proposed experiments will address the following specific aims: 1) to determine whether the changes in body fat experiments will address the following specific aims: 1) to determine whether the changes in body fat experiments will address the following specific aims: 1) to determine whether the changes in body fat distribution which occur with aging are associated with differences in systemic FFA availability, fatty acid oxidation, and regional adipose tissue meal fatty acid uptake; 2) to determine whether the change in fat distribution expected to occur with testosterone replacement therapy is associated with improvements in FFA metabolism, increased fatty acid oxidation, or changes in adipose tissue meal fatty acid uptake; 3) to determine whether DHEA replacement therapy in the elderly is associated with decreased body fat and upper-body fat and, if so, to assess DHEA's effects on FFA metabolism, fatty acid oxidation and regional adipose tissue meal fatty acid uptake. In order to address these specific aims we will use state-of-the-art body composition techniques, measures of adipose FFA release, assessments of fatty acid oxidation at rest, following meal consumption, and during exercise. In addition, we will apply a relatively new technique of determining regional adipose tissue meal fatty acid uptake to father information about potential mechanisms of fat redistribution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOCRINE ROLES OF STEROID 5 ALPHA REDUCTASE ISOZYMES Principal Investigator & Institution: Russell, David W.; Mcdermott Distinguished Professor; Molecular Genetics; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 31-MAR-2004 Summary: The overall objective of the proposed research is to gain insight into the biochemistry, function, and physiological roles of steroid 5alpha- reductase, an enzyme that plays crucial roles in the biosynthesis and breakdown of steroid hormones. In the first granting period, we isolated and characterized cDNAs and genes that encode two distinct isozymes of 5alpha-reductase, designated type 1 and type 2, which have different biochemical properties and tissue distributions. These findings raise a number of questions relating to the physiological roles of the two isozymes and how their different biochemical properties influence these roles. Our initial goal in the proposed studies will be a detailed analysis of the biochemical properties of the two isozymes. Two experimental approaches will be taken to this end, including the purification of the isozymes to homogeneity and the identification and characterization of naturally occurring mutations in the type 2 isozyme in subjects with the genetic disease 5alphareductase deficiency. Our second objective is to create and analyze mice that are

20

Testosterone

deficient in the 5alpha-reductase type 1 isozyme. As detailed in the Preliminary Results section, methods of targeted gene disruption have been used to generate mice that are heterozygous for a null allele at the type 1 locus. These animals will be bred to produce homozygous males and females that will be characterized at several different levels to determine the physiological role of this isozyme. Our third goal is to use similar methods to produce and characterize animals that are deficient in the 5alpha-reductase type 2 isozymes. Males homozygous for a type 2 null allele should represent a phenocopy of the human genetic disease of 5alpha-reductase deficiency, which is characterized by abnormalities in male phenotypic sexual development. Characterization of the type 2 deficient mice will provide insight into the physiological role of this isozyme in the development of the male phenotype and in the metabolism of steroid hormones. The final objective is to produce mice that are deficient in both 5alpha-reductase genes by crossing animals generated in Specific Aims 2 and 3. The resulting 5alpha-reductase deficient animals will be used to define the role of testosterone versus dihydrotestosterone in androgen action, to determine how fluctuations in the ratio of testosterone to estrogen impact on endocrine physiology, and to provide insight into the relative role of 5alpha-reduction in steroid hormone breakdown. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOGENOUS SEX HORMONES, GENETICS, AND PROSTATE CANCER Principal Investigator & Institution: Chen, Chu S.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 05-APR-1999; Project End 31-MAR-2003 Summary: Among American men, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death. Experimental and clinical evidence suggests that endogenous androgens could be contributors to the etiology of prostate cancer. However, epidemiologic studies have produced ambiguous findings. Some of these studies included a relatively small number of subjects, or have measured hormone levels following the diagnosis of prostate cancer. Even among the studies that have overcome these problems, none have examined a possible interaction between hormone levels and genetic determinants either of enzymes that influence hormone metabolism or of the androgen receptor on which these hormones act. We propose to conduct a casecontrol study nested within the Carotene and Retinol Efficacy Trial (CARET), a randomized control trial involving 18,314 participants. We will examine blood specimens obtained from approximately 300 CARET participants who developed prostate cancer at least six months after enrollment (which began in 1985) and 300 controls matched for age, race, time of blood draw, study center, and intervention arm. We will test the hypotheses that the risk of prostate cancer is related to: 1) serum concentrations of testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulfate, 3-alpha-androstanediol glucuronide, and estradiol; 2) polymorphisms of the 5 alpha-reductase type II gene, which may influence the ability of 5 alpha-reductase to convert testosterone into dihydrostestosterone, a more active androgen; and 3) polymorphisms of the androgen receptor gene, which may influence the sensitivity of the prostate to circulating and intraprostatic hormones. Because of the size of the proposed study, the measurement of hormone levels present at least six months before diagnosis, and the assessment of genetically-determined characteristics that may influence etiology (especially when considered jointly with hormone levels),

Studies

21

we believe the study has the potential to substantially advance our understanding of the etiology of prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF PUBERTAL HORMONAL CHANGES AND DEPRESSION Principal Investigator & Institution: Angold, Adrian C.; Associate Professor; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2003 Summary: (Adapted from the applicant's Abstract): This is a revised proposal to study biobehavioral aspects of mood disorders in girls. Specifically, it addresses the increase in rates of unipolar depression in girls that occurs during adolescence. We will contrast the effects of (1) age, (2) the development of secondary sex characteristics (Tannerstage) and (3) the effects of changing levels of six hormones -(a) from the pituitary, follicle stimulating hormone and luteinizing hormone, (b) estradiol (produced largely from the ovaries), and (c) testosterone, and rostenedione, and dehydroepiandrosterone-sulphate, which are produced largely from the adrenals in girls. Based on previous data from our group and a hierarchical model of puberty presented in the proposal, we predict that any apparent effects of age and/or Tannerstage will be better explained by underlying changes in testosterone and estradiol. Such a pattern of results would militate against theories attributing increases in rates of depression in adolescent girls to social effects generated by externally observable changes in secondary sex characteristics. The study is a unique opportunity to examine these issues because the psychiatric diagnostic data have already have been collected on a relatively large (N=438), representative, community sample of female children and adolescents, and the blood samples are already in hand. Funding is sought for two years of support for assay completion and data analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: FETAL ALCOHOL EXPOSURE--NEUROIMMUNE INTERACTIONS Principal Investigator & Institution: Taylor, Anna N.; Professor; Neurobiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUL-1994; Project End 31-MAR-2003 Summary: Fetal alcohol exposure (FAE) impairs the functioning of the immune system and decreases resistance to various infectious diseases. FAE also alters the development of neural and neuroendocrine systems, and thus may interfere with the bidirectional communications between the immune and the nervous system of offspring. Data indicate that FAE impairs the interactions between the immune and nervous systems. For example, we have shown that FAE blunts the febrile response induced by a pathogen product, lipopolysaccharide (LPS), and one of the cytokines, interleukin-1 beta (IL1), induced by LPS. Moreover, maternal adrenalectomy was found to prevent the blunted febrile response. The effects of FAE are probably mediated by developmentallyinduced alterations in brain mechanisms, since FAE also blunts the febrile response following intracerebroventricular (icv) administration of IL1. Given the essential role of fever in the host defense response to infection, we hypothesize that the attenuated febrile response following FAE reflects a general impairment in neuroimmune interactions which may contribute to the predisposition to infection resulting from FAE. One corollary hypothesis states that FAE affects the adult expression of neural

22

Testosterone

mediators of the febrile component of the acute phase response to infection. A second corollary hypothesis states that prevention of FAE-induced alterations in neuroimmune interactions mediating the febrile response to LPS can be achieved by hormonal manipulations pre-or postnatally. Specifically, we aim to: 1) Characterize the effects of LPS administered ip on certain mediators of the febrile response in adult male fetal alcohol-exposed and control rats, i.e., a) prostaglandin E2 (PGE), b) norepinephrine (NE), c) nitric oxide (NO), d) arginine vasopressin (AVP), e) alpha-melanocyte stimulating hormone (MSH), f) ACTH and corticosterone and g) IL1; 2) Investigate a possible role for neonatal or adult testosterone levels in mediating the effects of FAE on the LPS-induced febrile response and on its neurochemical mediators, as identified in Aim 1; and 3) Determine whether the prevention of the blunted LPS-induced febrile response by maternal adrenalectomy is (a) mediated by adreno-medullary or -cortical products, (b) is accompanied by changes in any of the neurochemical mediators of the febrile response identified as being affected by FAE in Aim 1, and (c) is accompanied by a reversal of the FAE-induced reduction in testosterone levels in neonatal and/or adult rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL OVARIAN HYPERANDROGENISM/MINORITY ADOLESCENTS Principal Investigator & Institution: Rieder, Jessica; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Functional Ovarian Hyperandrogenism (FOH), also called Polycystic Ovarian Syndrome (PCOS) consists of a spectrum of dysfunction with varying degrees of ovulatory dysfunction, hyperandrogenemia, and clinically evident hyperandrogenism. The biochemical and clinical criteria for hyperandrogenemia and hyperandrogenism have not yet been determined for a large ethnic minority female adolescent population. The specific aims of the study are: 1) to determine the relationship between the clinical presentation and the biochemical determinants of FOH/PCOS in a clinical sample of predominantly Caribbean-Hispanic and AfricanAmerican female adolescents; 2) to establish norms for the biochemical determinants of hyperandrogenemia in this population; 3) to determine the clinical correlates of hyperandrogenemia in adolescent girls; and 4) to determine if adolescent females with FOH/PCOS are more likely than normal, weight-matched adolescents to be CaribbeanHispanic, to have a family history of diabetes, high blood pressure or cardiovascular disease, or to have significantly higher glucose to insulin ratios. The hypotheses are as follows: 1) the testosterone and androstenedione levels in subjects with menstrual cycle abnormalities and/or physical evidence of hyperandrogenism will be significantly greater than in those with normal menstrual cycles and no physical evidence for hyperandrogenism; 2) a combination of clinical and historical features may be used to develop a model that can predict serum androgen levels; and 3) subjects with FOH/PCOS will be more likely than normal subjects to be of Caribbean-Hispanic descent, to have evidence of risk factors for diabetes mellitus and cardiovascular disease, and to have significantly higher glucose to insulin ratios. 250 females aged 12 to 21 will be consecutively recruited from several clinical sites; girls with chronic illnesses or on hormonally active drugs will be excluded. Subjects will complete a questionnaire to elicit features of menstrual and family history and will undergo a physical examination to evaluate for clinical signs of hyperandrogenism. Serum levels of fasting free and total testosterone, androstenedione, luteinizing hormone, follicle stimulating

Studies

23

hormone, insulin, 17-OH progesterone, and glucose will be measured. To determine the association of serum androgen levels with clinical features of FOH/PCOS, all subjects will be clinically stratified into three different categories and androgen levels will be compared among these groups, using ANOVA. Hyperandrogenism will be defined as two standard deviations above the mean testosterone and androstenedione levels in subjects with normal menstrual cycles and no physical evidence of hyperandrogenism (category I). A clinical prediction model for hyperandrogenemia will be developed using multiple linear regression analyses for androgen measures. A case-control study will be performed to determine differences between adolescent subjects with and without FOH/PCOS. Improved understanding of the boichemical and clinical features of FOH/PCOS in minority adolescents will facilitate the development of earlier treatment modalities and prevention of later serious health problems that result from the natural progression of this disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER AND PERINATAL ORIGINS OF ADULT DISEASE Principal Investigator & Institution: Woods, Lori L.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: Numerous human studies have shown that babies born smaller have an increased adult cardiovascular risk compared to larger babies, indicating that factors in the prenatal environment affecting fetal growth can program the individual for increased cardiovascular risk later in life. One of these factors is maternal protein intake. In rats, maternal protein restrict leads to renal dysfunction and hypertension in the adult offspring. Suppression of the intrarenal renin angiotensin system during a critical period in development, and a consequent reduction in nephron endowment, appear to play an important role in this programming. Female offspring are relative protected from the programming effects of several adverse maternal dietary conditions, including protein restriction. In other model, the presence of gonadal hormones during development and/or in adulthood contribute to the sexually dimorphic patterns of hypertension, but the mechanisms by which female gender protects against programming for hypertension by maternal diet are not known. The purpose of this project is to determine the mechanisms responsible for the relative protective effect of female gender on perinatal programming for hypertension. The overarching hypothesis is that the presence or absence of testosterone during development and/or testosterone during development and/or testosterone or estrogen later in life are responsible for the sexual dimorphism of perinatal programming, and specifically, that these gonadal hormones contribute to programming of offspring hypertension at least in part through permitting suppression of the fetal/newborn intrarenal renin-angiotensin system and consequent impairment of renal development, resulting in permanent changes in renal structure and function. In these studies, testosterone and estrogen levels in female offspring of normal and protein-restricted mothers will be manipulated during the developmental period and/or in adult life by orchiectomy/ovariectomy and administration of exogenous hormone or by administration of pharmacologic inhibitors. Renal reninangiotensin system components will be measured in the neonatal period, and arterial pressure, renal function, and glomerular number and volume will be measured in juvenile and adult animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

24

Testosterone

•

Project Title: GENDER DIFFERENCES IN STIMULANT ACTION Principal Investigator & Institution: Kuhn, Cynthia M.; Professor; Pharmacology and Cancer Biology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 15-MAR-1995; Project End 31-JAN-2002 Summary: Applicant's Abstract There has been little study of biologic factors which influence drug addiction in women. Recent studies suggest that women may be more sensitive to some effects of locomotor stimulants like cocaine. The purpose of the present proposal is to investigate possible biologic factors which might lead to differential effects of stimulants in males and females. Our previous studies have documented a robust gender difference in the locomotor response to cocaine in rats that is accompanied by markedly enhanced dopamine release as assessed with fast-scan cyclic voltammetry (FSCV) in intact brain and brain slices. The goal of the present proposal is to test the hypothesis that the integration of rapid membrane effects of estrogen on dopamine release and slow effects on dopamine transporter synthesis mediate the greater response of female rats to the locomotor stimulant actions of cocaine and the enhanced dopamine release that females demonstrate relative to males. To test this hypothesis, we plan to compare the ability of estrogen (E), progesterone (P), E+P or testosterone (T) receptors to influence locomotor responses to cocaine and dopamine release in ovariectomized (OVX) or castrated (CAS) rats, using dose response, time course and pharmacologic specificity studies of hormone effects. Dopamine uptake and release will be assessed using in vivo and in vitro FSCV. The last specific aim will address the related hypothesis that these effects of E, P or T are indirect, and mediated through central actions of CRF and/or corticosterone. These studies should provide insight into basic mechanisms which mediate gender differences in dopaminergic function and the effects of locomotor stimulants which depend upon dopaminergic transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GENETIC DETERMINANTS OF BRAIN SEXUAL DIFFERENTIATION Principal Investigator & Institution: Arnold, Arthur P.; Professor; Physiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: (applicant's abstract): The long term goal of the proposed studies is to understand the molecular signals that initiate sexually dimorphic development of the brain, and lead to sex differences in behavior. A great deal of experimental evidence indicates that one of these signals is testosterone, secreted by the testes before or after birth, which acts directly or indirectly on the brain of males to cause masculine patterns of neural development. However, some sex differences in the brain are not induced by gonadal steroids, and the proposed studies test an alternative hypothesis, that genes on the sex chromosomes are differentially expressed in male and female brain and lead, via non- hormonal mechanisms, to sex differences in neural development and behavior. To analyze this hypothesis, we will measure various parameters of brain structure and function, and of behavior, in male and female mice of selected genotypes that carry different numbers of X and Y chromosomes, or different portion of the sex chromosomes in varying numbers. The parameters to be measured are known sexual dimorphisms in brain structure and function and behavior. The proposed studies will determine if any genes on the Y or X chromosome contribute to sex differences in neural and behavioral development, and will narrow down the location of these genes to specific regions of the

Studies

25

sex chromosomes. The proposed research will contribute significantly to an understanding of the principles of sexual differentiation of the brain. At issue are the molecular mechanisms by which male and female brains differ, which is highly relevant to biological basis of abnormalities of sexual differentiation, and to the explanation of sex differences in psychiatric and neural disease (e.g., Alzheimer's Disease and Multiple Sclerosis). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GONADOTROPIN /INSULILN INTERACTIONS IN PCOS Principal Investigator & Institution: Rosenfield, Robert L.; Professor of Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 28-APR-2003; Project End 31-MAR-2008 Summary: Polycystic ovary syndrome (PCOS) is a poorly undcrstood disorder which seems to be due to dysregulation of steroidogenesis, resulting in a high serum testosterone level. A promoter variant of 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5), a major determinant of ovarian testosterone formation, contributes to testosterone excess in PCOS. We propose to test the concept that 17beta-HSD5 activating variants interact with specific endocrine factors to determine ovarian testosterone secretion in both normal and PCOS patients in a clinical research project that will manipulate LH, insulin, and FSH levels. The specific aim is to test the hypothesis that the phenotype of an activating variant of the 17beta-HSD5 gene depends on interaction with LH, insulin resistant hyperinsulinemia, and FSH-dependent granulosa cell factors. The sub-aims are to ascertain the role of the variant genotype: 1) as a determinant of ovarian testosterone secretion in response to LH in normal and PCOS subjects, 2) as a determinant of ovarian testosterone secretion in response to insulin excess in PCOS, and 3) as a determinant of ovarian testosterone secretion in response to FSH-inducable ovarian factors. We will begin by determining the testosterone response to the LH analog human chorionic gonadotropin (hCG) in PCOS and control women of known 17beta-HSD5 genotype at the "A/G" promoter site. Then we will determine the effects of suppressing gonadotropins with a GnRH agonist, suppressing insulin with a thiazolidinedione (TZD), and stimulating granulosa cell function with FSH. The effects of the TZD on LH pulse characteristics and indexes of insulin secretion/sensitivity will also be assessed. The primary endpoint is the testosterone response to hCG, which will be related by analysis of variance to the 17beta-HSD5 genotype. If our hypothesis is correct, we expect LH, insulin, and inhibin B levels to be related to successively higher testosterone responses to hCG in subjects lacking, heterozygous, and homozygous for activating 17beta-HSD5 variants. If the data support the hypothesis, it would be the first direct evidence for a specific PCOS phenotype (ovarian testosterone secretion) resulting from interactions between a specific genetic trait (17beta-HSD5 variant) and the endocrine mileau (e.g., with respect to LH, insulin, and FSH levels). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HIV RISK BEHAVIOR AND VIOLENCE AMONG CRACK USERS Principal Investigator & Institution: Logan, Tk; Psychiatry; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 15-AUG-1998; Project End 31-JUL-2003 Summary: (Applicant's Abstract) The overall aim of this study is to examine the nature, extent, and co-occurrence of HIV risk behavior, violence, and crack use by extending

26

Testosterone

data collection from crack users (n=300) previously enrolled in a National Institute on Drug Abuse (NIDA) funded AIDS Cooperative Agreement study in Kentucky. Crack users are a critical group to focus on given their risk for both violence and HIV risk behavior. The specific aims of this study are: (1) To examine the onset, escalation, and cessation of crack use and the nature, extent, and pattern of occurring violence, violent victimization, and HIV risk behavior among crack users; (2) To examine the association of antisocial personality disorder, impulsivity, anxiety, depression, anger, hostility, serotonin, and testosterone with violence and HIV risk behavior among crack users; (3) To examine the importance of violent victimization, post traumatic stress disorder, and depression to HIV risk behavior among crack users; (4) To examine the impact of stress/strain and the interaction of negative affect (e.g., anger, depression, and anxiety) and stress-coping styles on violence and HIV risk behavior as outcome variables; and, (5) To continue data collection on patterns of crack use, treatment, criminal justice experience, and HIV risk behavior among crack users previously enrolled in the NIDA AIDS Cooperative Agreement study in Kentucky for 300 crack users. The primary reason for using a subsample of crack users previously enrolled in the NIDA AIDS cooperative agreement is that the subsample of crack users can be characterized on patterns and history of crack use and HIV risk behavior using a standardized and validated interview protocol, the Risk Behavioral Assessment (RBA), which is critical for this study. This study proposes to use face-to-face interviews to construct life history calendars for violence, violent victimization, crack/other drug use, and HIV risk behavior. Measures are also proposed to collect information about individual difference and biochemical variables among male (n=150) and female (n=150) crack users. The protocol is estimated to last approximately three hours. Life events analysis, structural equation modeling, and regression are proposed as the major analytic techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL CARCINOGENESIS IN RB-KNOCKOUT MOUSE PROSTATE Principal Investigator & Institution: Hayward, Simon W.; Assistant Professor; Surgery; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: The overall objective of this work is to enhance the understanding of prostate cancer initiation and progression. The main goal of the present proposal is to characterize new models of hormonal carcinogenesis in the mouse prostate. These experiments will use retinoblastoma (Rb) gene-knockout and conditionally deleted-Rb mouse prostate as a target for hormonal carcinogenesis. Experiments will examine the ontogeny and histopathology of carcinogenesis (aim 1), the precise role played by sex steroids (aim 2) and the specific epithelial cell type targeted by hormonal carcinogens (aim 3). A panel of cell strains will be derived from the tumors which are generated. Their behavior in vivo will be characterized and they will be subject to genomic analysis to identify common genetic lesions associated with prostate cancer (aim 4). Data from these studies will be used to identify candidate genes involved in prostatic carcinogenesis. The central hypothesis is that the progression from normal histology to cancer seen in mouse prostatic tissue lacking expression of the Rb tumor-suppressor gene is a good in vivo model of human prostate cancer. This project will use two new in vivo models of prostatic carcinogenesis. The first is a tissue recombination model based upon prostatic epithelium derived from the Rb-knockout mouse. The second model is a conditional deletion of Rb in the luminal epithelial cells of the prostate utilizing cre-lox technology. In both models a combination of testosterone and estradiol will be used to

Studies

27

initiate the formation of prostate tumors. Prostate tumors will be used to generate a spectrum of cell lines representative of the stages from normal prostate to hormoneindependent prostate cancer. These cell lines will serve as a source material to examine genomic lesions associated with prostate cancer progression. The following specific aims will be pursued. Specific Aim 1 Characterization of tumor progression in Rb-deficient mouse prostate under the influence of testosterone and estradiol. Specific Aim 2 An examination of the roles of testosterone and estradiol in hormonally induced prostatic carcinogenesis in the Rb-deficient mouse prostate Specific Aim 3 Generation and Characterization of ARR2Pb-cre RbloxP/loxP mice. Hormonal Carcinogenesis in ARR2Pb-cre RbloxP/loxP mice. Specific Aim 4 Isolation, phenotypic and genomic characterization of Rb-deficient cell strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL CONTROL OF HUMAN TESTICULAR FUNCTION Principal Investigator & Institution: Bremner, William J.; Chief; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAR-2006 Summary: The general objective of this work is to define carefully the endocrine milieu that is required to maintain normal testicular function in men. In particular, we are concerned with the gonadotropin and steroid environment necessary to stimulate human spermatogenesis and steroidogenesis. We will be experimentally manipulating the hormonal environment of the testis in normal men and determining the resultant effects on spermatogenesis and steroid production. More specifically, the objectives of this work are to anser questions in four areas: 1. What are the physiological roles of follicle-stimulating hormone (FSH) in men? Is FSH required to maintain spermatogenesis in man? 2. What are the physiological roles of luteinizing hormone (LH) in men? Is LH required to maintain human pituitary stimulatory effect on testicular steroid secretion? 3. Is the conversion of testosterone (T) to dihydrotestosterone (DHT) i.e. 5alpha reduction, important in the stimulation of human spermatogenesis? What are the concentrations of T and DHT in the human testis in various experimental paradigms, and doses this information advance our understanding of the control of spermatogenesis. 4. Can the new gene array technology be applied successfully to studies of the human testis; if so, will this new technology yield additional insights into the genes controlling human spermatogenesis and steroidogenesis? This work will make use of new compounds, including recombinant human FSH and LH, a gonadotropin releasing hormone (GnRH) antagonist and a 5alpha reductase inhibitor, for exploring the normal physiologic control systems of human testicular function. Our studies are directly relevant to the development of safe, effective, reversible methods of male contraception and to the treatment of men disorders of spermatogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HORMONAL INDUCTION ANIMAL MODEL OF PROSTATE CANCER Principal Investigator & Institution: Bosland, Maarten C.; Professor of Environmental Med. & Urolog; Environmental Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 12-JAN-1999; Project End 31-DEC-2002

28

Testosterone

Summary: Combined treatment with testosterone (T) + estradiol-17beta (E2) induces prostate adenocarcinomas in 100 percent of NBL rats, and T alone a 40 percent incidence. This is the only model in which steroid hormones alone produce a high prostate cancer incidence; it offers opportunities to study the mechanisms whereby steroid hormones cause prostate cancer. We hypothesize that E2, either formed endogenously from T by the enzyme aromatase or exogenously administered, acts via a genotoxic mechanism that involves the generation of reactive oxygen species to produce prostate carcinomas in the presence of T, and that estrogen receptor (ER)-mediated mechanisms are not involved. To address the hypothesis and resolve some uncertainties about the model, the following specific aims are proposed. Aim 1: To establish whether E2 is an essential factor in the hormonal induction of prostate cancer by T, and whether it acts via a mechanism that is ER-independent; we will establish whether treatment with an aromatase inhibitor reduces or eliminates prostate cancer induction by T, and to demonstrate that antiestrogen treatment does not affect the tumor response. Aim 2: To determine whether induction of oxidative DNA damage and of prostate carcinomas by T and E2 are linked and, therefore, probably causally related; we will administer antioxidant vitamins (C and E) to T+E2-treated rats, which should reduce both prostate cancer induction and prostatic oxidative DNA damage (measured by formation of 8hydroxydeoxyguanosine). Aim 3: To demonstrate that T+E2-induced carcinomas have the potential to metastasize and determine whether T+E2-induced peripheral prostate dysplasia can progress to cancer; we will determine whether lowering of the E2 dose or shortening of the E2 treatment duration, while continuing T administration, will sufficiently lower or delay pituitary tumor formation and prolong survival to allow progression of prostate carcinomas to the metastatic stage. Aim 4: To establish whether T+E2- induced prostate carcinomas are androgen-sensitive and their induction is androgen-dependent and prolactin-independent; we will test the response of prostate cancers transplanted into syngeneic rats to castration and determining the effect of castration of T+E2-treated rats at a time at which very small carcinomas have already formed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL REGULATORS OF MUSCLE AND METABOLISM IN AGING Principal Investigator & Institution: Sattler, Fred R.; Professor of Medicine; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant) Elderly persons experience progressive loss of skeletal muscle mass, muscle strength, and functional capacity for activities of daily living. Aging is also associated with a loss of gonadal function and integrity of the growth hormone (GH)/IGF-1 axis. However, the relationship of deficiencies in these hormonal axes to sarcopenia and functional impairment in aging has not been established or whether there is an interaction of these two hormone systems in maintaining normal skeletal muscle mass and physical function. We hypothesize that both hormone systems regulate musculoskeletal protein mass and contractile fibers by different and complimentary mechanisms and that optimal levels of both testosterone and GH are necessary to maintain skeletal muscle mass, muscular strength and power, and full functional activities of daily living during the aging process. This proposal has been revised and entails a controlled, 16 week study to evaluate the independent effects and interaction of these two anabolic hormone systems in community dwelling elderly men 65-90 years of age who are hyposomatotropic (IGF-1 in lower tertile) with low

Studies

29

eugonadal status (total testosterone of 250-550 ng/dL). The study will utilize a factorial design (2X3) with a two tiered randomization in which 108 study subjects will first be randomized to either the low or high eugonadal level of testosterone using a novel Leydig cell clamp method (GnRH agonist plus topical testosterone supplementation) to achieve target levels of testosterone. Low gonadal status (250-550 ng/dL) will be maintained with 5 g daily doses of topical testosterone, whereas high gonadal status (650-950 ng/dL) will be achieved with 10 g daily doses. Within these two groups, subjects will be randomized to receive placebo or one of two doses of rhGH therapy (0, 3.0, 5.0 mug/kg/day) in a double blinded fashion. The direct effects of study interventions will be assessed by measuring the fractional synthetic rates of mixed and contractile (actin and myosin heavy chain [MHC]) skeletal muscle proteins and degradation of skeletal muscle (ubiquitin, and proteasome sub-units) and by analyzing local regulators of skeletal muscle synthesis (e.g. IGF- I, IGFBP4, myostatin). The clinical effects resulting from the study interventions will be assessed by measuring change in skeletal muscle strength, muscle mass, power and fatigability (endurance), physical performance, and markers of safety. The findings of this study should result in important mechanistic understanding of the relative contributions of androgen deficiency and hyposomatotropism in elderly persons with or who are at risk for frailty due to decreased muscle mass and strength. The results should also provide valuable information for future testing of new, novel treatment strategies, which are more tolerable and convenient than parenteral therapies for age associated sarcopenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IGF-1 AND BONE LOSS IN WOMEN ANOREXIA NERVOSA Principal Investigator & Institution: Klibanski, Anne; Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 19-MAY-1997; Project End 31-AUG-2008 Summary: (provided by applicant): Anorexia nervosa is an increasingly common disorder among young women, characterized by self-imposed restrictive nutritional practices, which occurs in 0.5 to 1% of college-age women in the United States. This psychiatric disorder results in significant medical complications, which cause morbidity and increased mortality. Bone loss is a severe, frequent and often permanent co-morbid medical complication of anorexia nervosa, resulting in crush fractures. The majority of young women have evidence of bone loss and 50% of women have bone density measurements greater than 2 SD below normal and below the fracture threshold. The extreme rapidity of bone loss in anorexia nervosa is well documented. Of importance, bone loss can occur in less than one year. Reduced bone mass is often permanent, despite recovery and such young women will have a permanent increased risk of fractures throughout life. Anorexia nervosa is a unique state of imbalanced bone turnover with decreased bone formation and increased resorption. In contrast to other states of bone loss associated with estrogen deficiency, estrogen therapy is ineffective in stabilizing or improving bone mass. Therefore, the bone loss seen in anorexia nervosa is unique in terms of severity and pathogenesis. Given the complex medical issues in patients with this disorder, approaches to the prevention and treatment of osteoporosis differ from other populations. Effective therapy of bone loss during acute illness would reduce fracture risk throughout life. Of importance, a therapeutic intervention may only need to be used for a relatively short period of time while the disease is still active in many patients. Because there are currently no treatments for this serious medical sequelae of anorexia nervosa, it is critical to develop efficacious treatment strategies to prevent the significant morbidity associated with osteopenia in this population.

30

Testosterone

Testosterone is a nutritionally regulated endogenous anabolic hormone which stimulates bone formation and has anti-resorptive effects. Anorexia nervosa leads directly to testosterone deficiency. We hypothesize that testosterone plays a critical role in bone turnover and long-term, it's administration will improve bone density and prevent the progressive debilitating osteopenia in young women with anorexia nervosa. We have now demonstrated an effect of short-term testosterone administration to increase markers of bone formation and/or resorption. Because of its effects on bone formation, testosterone may represent a novel approach to treating the severe osteoporosis resulting from anorexia nervosa in young women. We now have preliminary data demonstrating that Actonel, a bisphosphonate, can decrease bone resorption and increase bone mass in these women. In the current proposal we will investigate the physiology of the effects of testosterone administration of rhlGF-I to reverse the androgen deficiency state. We will investigate the effects of testosterone on bone turnover and whether it has prolonged effects on bone density. We will determine whether a combined anabolic and anti-resorptive strategy using testosterone and Actonel will increase bone formation, decrease resorption and increase bone density. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF PUBERTY ON THE KIDNEY IN DIABETES Principal Investigator & Institution: Lane, Pascale H.; Pediatrics; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The prepubertal years of type 1 diabetes (DM) appear to be protected from expression of nephropathy and other microvascular complications. Only post-pubertal male rats given the diabetogenic agent streptozocin (STZ) develop renal and glomerular hypertrophy associated with increased expression and activity of transforming growth factor b (TGFb). Prepubertal rats do not develop hypertrophy or upregulation of the TGF system. Given clinical differences in the prevalence and rate of progression between the sexes, gonadal steroids seem likely to be involved in these processes. Overall hypothesis: Androgen synthesis that accompanies puberty contributes to the development of diabetic nephropathy via changes in the renal transforming growth factor (TGF(3) system. Specific Aims: I) What are the roles of androgens in diabetic kidney disease? 1)Examine sex differences in the renal reponse to STZ DM; 2)Examine the effects of gonadectomy on the post-pubertal renal response to STZ DM; 3)Determine the effect of testosterone treatment on the renal response to STZ DM; 4)Determine the role of the androgen receptor in the renal response to DM; and 5)Determine whether conversion to dihydrotestosterone is necessary for the postpubertal renal response to STZ DM. II) What is the mechanism through which puberty promotes TGFfi expression/activation? 1 )Examine the renin-angiotensin system in response to pre- and post-pubertal states and hormonal manipulation; 2)Examine the protein kinase C system in response to pre- and post-pubertal states and hormonal manipulation; 3)Examine the oxidative stress system in response to pre- and postpubertal states and hormonal manipulation; 4)Define the direct effects of sex steroids in vitro on the oxidative stress pathway; and 5)Define the direct effects of sex steroids in vitro on the PKC pathway. Methods: Rats will be given STZ DM pre- or post-puberty for 6 weeks, a duration of DM which increases TGFI3 expression and renal weight in adults. Groups will include males and females with and without earlier gonadectomy. Some groups will also receive treatment with testosterone, flutamide, an androgen receptor blocker, or finasteride, which blocks conversion of testosterone to dihydrotestosterone. in vitro studies will involve kidney slice cultures from 10 week old castrated male rats,

Studies

31

with or without prior induction of OM. Media will include normal or high glucose conditions, as well as variable amounts of testosterone or estrogen. Measurements will include TGFJ3 proteins by ELISA and nitric oxide synthase isoforms, angiotensin II receptor, and protein kinase C isoforms by immunoblotting; superoxide generation; nitric oxide synthase activity; protein kinase C activity; mRNA for TGFb, nitric oxide synthases, and TGFb inducible gene-H3 by RT-PCR; plasma and renal levels of angiotensin II; and blood levels of sex steroids by RIA. Health implications: New treatments to prevent diabetic kidney disease, the most important cause of kidney failure in the US, may emerge from a better understanding of a naturally protected state such as the prepubertal animal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INCREASED GLUCONEOGENESIS IS ONE CAUSE OF CFRD Principal Investigator & Institution: Hardin, Dana S.; Associate Professor; Pediatrics; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The incidence of impaired glucose tolerance and diabetes (called CFRD) is high in cystic fibrosis (CF), and is expected to increase due to increased life-span of the patients. CFRD is an important cause of worsened morbidity and mortality, thus understanding the pathophysiology underlying its development is imperative. Insulin deficiency has been recognized as one cause of CFRD; however it is clear the etiology is more complex. The applicant's long-range goal is to understand the pathophysiologic changes which cause CFRD. Studies proposed in this application will allow us to characterize alterations in normal metabolism of glucose and protein which contribute to CFRD. Our global hypothesis is that increased rates of gluconeogenesis (GNG) result in hyperglycemia. This excess is not caused simply by portal hypoinsulinemia alone, but rather is driven by excessive amino acid substrate availability secondary to cytokinemediated protein catabolism. We will recruit 48 adult CF subjects (12 per glucose tolerance category: normal, impaired, CFRD with fasting hyperglycemia and CFRD without fasting hyperglycemia) and 20 normal volunteers matched for age and gender. Subjects will recruited from the CF centers at The University and the South Central CF Consortium (all CF centers in Texas, Oklahoma and Arkansas). Subjects will be categorized according to clinical status (pulmonary function and modified NIH score), and we will measure cytokines TNF-a, IL- 6, IL-10 and TNF receptor antibodies. We will also measure thyroid function, estrogen and testosterone and IGF-1 levels. GNG and glycogenolysis will be quantified by measuring the incorporation 2H into the 2nd, 5th and 6th carbons of glucose, and reported as percentage of total hepatic glucose production (measured using [6,6-2H2]glucose). Whole body protein turnover (WBPT) will be measured using [15N]urea and [1-13C]leucine, and we will conduct a sub-study to evaluate the effect of intravenous protein hyperalimentation on GNG and WBPT. Insulin secretion will be quantified using a hyperglycemic clamp (target glucose levels 160 mg/dl and 350 mg/dl). Insulin effect on GNG and WBPT, as well as peripheral insulin sensitivity will be determined using a step-wise hyperinsulinemic euglycemic clamp (insulin doses of 10,20 and 120 mU/m2/min). We will measure resting energy expenditure using indirect calorimetry and intake of carbohydrate, protein and fat will be quantified with a three day food journal. Important support for this proposal includes the excellent scientific community at UT-Southwestern, the consultant role of Dr. Satish Kalhan, a noted expert in substrate metabolism, ready access to a GC mass spectrometer, institutional support, and an established track record of performing complex metabolic studies in CF subjects. It is therefore expected that these studies will

32

Testosterone

provide new information regarding potential causes of CF related diabetes and protein catabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITORY AND INDUCING EFFECTS OF HERBAL MEDICINES ON CYP ENZYMES Principal Investigator & Institution: Edeki, Timi I.; Associate Professor; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-JUL-2006 Summary: (provided by applicant): In recent years there has been an increased consumption of herbal medicines. Most of those that take these medicines also consume other conventional medicines, and do not inform their physicians about the use of herbal medicines and other alternate medical practice. In addition, most of these herbal medicines have not been rigorously studied and have not been subjected to the same standards as conventional medicines. As a result of this, there is a dearth of information on possible interactions between herbal products and drugs. Contrary to the opinion of most consumers that these herbal products are benign, a number of interactions have recently been reported between herbal medicines and conventional drugs. This increased use of herbal medicines exposes a significant percentage of the population to unknown herb drug interactions. Our hypotheses are that the metabolism of drugs mediated by cytochrome P450 (CYP) enzymes, can be modulated by ingestion of herbal medicines such as ginseng, ginkgo biloba and St. John's wart, and that ethnicity is a factor in this modulation. The resulting induction or inhibition will therefore affect the metabolism of the drugs that are substrates of these enzymes. Since many clinically important drugs are CYP substrates, there are implications for herb-drug interactions. In light of the above, the specific aims of this grant proposal are the realization of the following objectives: 1) To determine if the active pharmaceutical ingredients of American ginseng, Korean ginseng, gingko biloba and St. John's wart inhibit CYP2C9, CYP2C19, CYP2D6, and CYP3A4 activities, with tolbutamide, mephenytoin, bufuralol and testosterone as an in vitro probes, using microsomes prepared from human liver. 2) To determine if genotype is a factor on these inhibitory effects. 3) To determine the inducing or inhibiting effects of the important components of St. John's wart, American ginseng, Korean ginseng and gingko biloba on CYP2C9, CYP2C 19, CYP2D6, CYP3A activities in human hepatocytes obtained from Caucasians and African Americans. 4) To determine if there are interethnic differences between African Americans and Caucasians in the possible CYP enzymes modulating effects of herbal medicines in human hepatocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: INTERPLAY BETWEEN GONADAL STEROIDS AND INSULIN IN MEN Principal Investigator & Institution: Hayes, Frances J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAR-2005 Summary: (taken from the application) The overall goal of this proposal is to define the causal determinants of the inverse relationship between insulin resistance and testosterone in men. Conducting studies in normal men, lean first degree relatives of type II diabetic patients, obese men with normal glucose tolerance, and men with type II diabetes will permit determination of whether the interaction between insulin resistance

Studies

33

and testosterone is independent of body weight and glucose tolerance. Given the significant cardiovascular morbidity and mortality associated with obesity and type II diabetes, a clearer understanding of the interplay between testosterone and insulin resistance has important public health implications and may potentially facilitate the development of new therapeutic strategies for these extremely common metabolic disorders. Specific Aims 1-3 of this proposal will address the impact of insulin resistance on the reproductive axis in the male and will specifically: i) define the dose response relationship between increasing insulin resistance and testosterone secretion in men; ii) localize the defect induced in the hypothalamic-pituitary-gonadal (HPG) axis by insulin resistance using frequent blood sampling studies as well as GnRH and hCG testing after endogenous gonadotropin blockade with a GnRH antagonist; and iii) examine the impact on the HPG axis of reducing insulin resistance with a thiazolidinedione in men with type II diabetes. Specific Aims 4 and 5 will address the impact of testosterone on insulin resistance and will specifically: iv) define the dose-response relationship between increasing testosterone and insulin resistance by measuring insulin sensitivity with a glucose clamp after induction of hypogonadism with a GnRH agonist and again after both physiologic and pharmacologic testosterone replacement; and v) examine the impact of testosterone treatment on insulin resistance and glycemic control in type II diabetes. The selective and sequential manipulation of sex steroid and insulin levels as outlined in this proposal will permit precise definition of the relationship between testosterone and insulin resistance in men to be established and their causative determinants unequivocally defined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LHRH SYNTHETIC PEPTIDE VACCINE FOR PROSTATE CANCER Principal Investigator & Institution: Finstad, Connie L.; United Biomedical, Inc. 25 Davids Dr Hauppauge, Ny 11788 Timing: Fiscal Year 2002; Project Start 10-SEP-1999; Project End 31-MAY-2004 Summary: United Biomedical, Inc, (UBI) has developed an alternative approach to injectable LHRH agonists and other androgen-ablation therapies for the treatment of prostate cancer through development of an anti-LHRH immune response. The LHRH synthetic peptide vaccine comprises the LHRH decapeptide covalently linked to helper T cell epitopes and to an additional peptide that provides specific immune adjuvanting activities. This molecular conformation produces a potent B cell response and antiLHRH antibodies in sufficiently high titer to neutralize circulating LHRH and thereby suppress androgen production. Studies in rodents have demonstrated that the LHRH peptide vaccine can rouse a specific immune response that inhibits and androgendependent tumor growth in the host by blocking synthesis of testosterone. The goal is to evaluate the efficacy and safety of the LHRH peptide vaccine prepared in several adjuvant formulations to induce antibody adult male baboons. If successful, these preclinical studies will provide supporting data for an IND application and the testing of the LHRH peptide vaccine formulation as an alternative hormonal ablative therapy for prostate cancer. PROPOSED COMMERCIAL APPLICATIONS: The LHRH synthetic peptide vaccine is an immunotherapy for the treatment of androgen-responsive, advanced prostate cancer. This vaccine is predicted to be effective because its mode of action is analogous to the LHRH agonist-androgen-ablation therapies currently used to treat prostate cancer as well as other hormone-responsive benign conditions and tumors (e.g., endometriosis, leiomyoma). Commercial advantages of the LHRH vaccine therapy over agonists include improved patient compliance and less costly treatment option. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

34

Testosterone

•

Project Title: MACROPHAGE DERIVED FACTOR AND LEYDIG CELL FUNCTION Principal Investigator & Institution: Hutson, James C.; Cell Biology and Biochemistry; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: It has long been established that in the absence of LH, as occurs in hypophysectomized animals, Leydig cell development and function are drastically altered. However, it has recently been shown that even when LH is present, Leydig cells produce far less testosterone when macrophages are depleted from the testis. Similarly, when macrophages are depleted from the testis of immature animals, Leydig cells fail to develop properly. Thus testicular macrophages, like LH, are essential for normal function of Leydig cells. We have partially purified and characterized a lipophilic factor secreted by macrophages that stimulates testosterone production by Leydig cells. We hypothesize that this factor mediates some of the actions that macrophages exert on Leydig cells that have been described in these macrophage-depletion studies, including a role in Leydig cell maturation, stimulation of testosterone production, and involvement in maintaining LH- responsiveness. Thus this factor has the potential to be of great physiological significance. In Aim 1 we propose to use mass spectroscopy, nuclear magnetic resonance, and other physico-chemical approaches to identify the chemical structure of this factor. A CoPI and a collaborator have been added to the proposal as recommended who have expertise in this area. In Aim 2, we will continue studies concerning the mechanism of action of the factor. We have found that the factor elicits a greater response than does LH/hCG, does not require new synthesis of StAR, does not act directly on mitochondria, is not itself a substrate for steroidogenesis, and exerts its influence proximal to cholesterol sidechain cleavage, all indicating that its mode of action is very different than that of LH. We now propose to determine if the factor activates protein kinase A and/or C, causes changes in calcium metabolism, and/or changes in intracellular levels of cAMP. In Aim 3, we will determine if the factor is produced by testicular macrophages from immature animals. If so, we will then test its ability to induce maturation of postnatal Leydig cells. Finally, we will determine if the factor can restore Leydig cell function (testosterone production and ability to respond to LH) in macrophage- depleted animals. These gain-of-function studies will determine the physiological significance of this factor, and if positive results are obtained, new opportunities to treat infertility and/or create new male contraceptives may emerge, since testicular macrophages are present in high numbers in humans as they are in rodents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MECHANISMS OF CYTOCHROME P450 ALLOSTERY Principal Investigator & Institution: Atkins, William M.; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Many drug-drug interactions are metabolic in origin, resulting from the activation or inhibition of Cytochrome P450 (CYP)-dependent drug clearance. A potential contribution to CYP-dependent drug interactions is the poorly characterized allostery that is widely observed in vitro, and also in vivo. This allostery includes nonhyperbolic steady state kinetic profiles for individual substrates (homotropic allostery), as well as alterations in the kinetic profiles of one drug by a second (heterotropic allostery). The molecular mechanisms leading to allostery are not defined, although several contrasting models have been proposed and include multiple ligand binding

Studies

35

within a single fluid active site, multiple ligand binding within discrete subsites of this large active site, and ligand-dependent persistent protein conformational equilibria. Here, non-steady state kinetic methods will be exploited to challenge these models and to understand CYP allostery in the context of existing structural models for CYP3A4 and CYP2C9. The specific aims are: 1) to determine whether the elementary steps of ligand binding, ligand-dependent ferric spin state equilibrium, or ligand-dependent changes in gross protein conformation are differentially allosteric for the homotropic effects of testosterone, pyrene, and hypericin with CYP3A4; 2) to determine by paramagnetically shifted 1H-NMR spectra, the mechanism of allostery for the heterotropic effects between caffeine and acetaminophen or midazolam and alpha-naptho flavors with CYP3A4, and to initiate SAR-by-NMR to map ligand binding sites in uniformly deuterated, 15N-Phelabeled CYP3A4; 3) to monitor conformational dynamics of CYP3A4 via limited proteolysis/electrospray mass spectrometry as a function of ferric/ferrous redox state and ligand binding; 4) to map the CYP3A4/Cyt b5 binding surface via site-directed mutagenesis and catatylic turnover experiments, and determine whether specific interfacial residues contribute to Cyt b5-dependent allosteric effects. In addition, where possible, parallel experiments will be performed with CYPeryF, a soluble homolog for which X-ray crystallographic analysis is possible. In the long term, x-ray structures of [CYPeryF.ligand] complexes will be sought, via collaboration, in order to correlate allosteric effects with CYP structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF METASTASIS IN EXPERIMENTAL PROSTATE CANCER Principal Investigator & Institution: Thompson, Timothy; Associate Professor; Urology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-AUG-1995; Project End 31-MAY-2005 Summary: (Adapted from the investigator's abstract) The high level of mortality from prostate cancer results from the inexorable growth of overt or occult metastases that ultimately manifest as androgen resistant disease. To better understand the metastatic phenotype in prostate cancer, he developed a strategy to identify mRNAs that are expressed differentially in cell lines derived from primary versus metastatic mouse prostate cancer using differential display-PCR. In using this system, a number of metastasis-related genes were identified including a cDNA that encodes caveolin-1. Caveolin-1 was found to be overexpressed not only in metastatic mouse prostate cancer, but also in human metastatic disease and was shown to be an independent predictor of recurrent following radical prostatectomy. Suppression of caveolin-1 expression induces androgen sensitivity in high caveolin-1, androgen-insensitive mouse prostate cancer cells derived from metastases. Conversely, overexpression of caveolin-1 leads to androgen instensitivity in low caveolin-1 androgen-sensitive mouse prostate cancer cells. He demonstrate that testosterone induces caveolin-1 expression through transcriptional regulation, and that caveolin-1 is a downstream effector for testosteroneinduced survival in mouse prostate cancer cells in vitro. He has confirmed in human prostate cancer specimens that caveolin-1 expression is significantly increased in both primary tumors and their metastases following chemical and surgical androgen ablation, and preliminary studies suggest specific growth factors may induce caveolin-1 expression in the absence of testosterone sustaining cell survival. A critical molecular link between caveolin-1 and prostate cancer progression was established through the discovery that c-myc overexpression leads to downregulation of caveoline-1 blocks cmyc-induced apoptosis in vitro. He now proposes to characterize the regulation of

36

Testosterone

caveolin-1 gene expression in prostate cancer by gene methylation, testosterone and growth factor-mediated mechanisms. He will also define the cis-acting regulatory elements in the mouse caveolin-1 promoter that mediate transcriptional activation. Based on preliminary data that indicate caveolin-1 can specifically protect against thapsigargin-induced cell death, he will map the biochemical blocks generated by caveolin-1. Finally, he will test the potential cooperative activities of c-myc and caveolin1 in promoting malignant progression in vitro and in vivo using an LNCaP-mycER system and transgenic prostate and mouse models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF SEX-DETERMINED RESISTANCE TO L. MEXICANA Principal Investigator & Institution: Satoskar, Abhay R.; Assistant Professor; Microbiology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Sex hormones have been shown to have a profound influence on modulation of immune responses and the outcome of various diseases in males and females. We have found that female mice are relatively more resistant visceral and cutaneous leishmaniasis than the male mice. In the L. mexicana model, we found that female DBA/2 mice mount an efficient Th1-like response and develop smaller lesions than the male mice that develop large, non-healing lesions. Moreover, we also found that ovactomized female DBA/2 mice treated with dihydrotestosterone (DHT); a derivative of testosterone that can not be converted to estradiol, become susceptible to L. mexicana whereas castrated male mice treated with 17-beta-estradiol become resistant. These findings suggest that while estrogen plays a critical role in induction of protective immunity against L. mexicana, testosterone may be detrimental. Despite these findings it is not clear how sex hormones (estrogen and testosterone) regulate immune responses during L. mexicana infection. Our long term goal is to understand the immunological mechanisms responsible for gender dimorphism in susceptibility of mice to different Leishmania species. In this project, we propose to determine how these sex hormones (estrogen and testosterone) regulate in vivo immune responses and influence the outcome of cutaneous leishmaniasis caused by L. mexicana. The first specific aim would determine how estrogen induces the development of protective immunity against L. mexicana. The studies proposed in the second specific aim would determine how testosterone prevents development of protective immune response and mediates susceptibility to L. mexicana. The third specific aim will focus on studies using bone marrow chimeras to determine whether endogenous sex hormones regulate functional development of T cells in vivo and affects their ability to differentiate into Th1 or Th2 subsets The experiments proposed in this project are designed to investigate several potential mechanisms of the protective effects of estrogen (17-beta-estradiol) and the susceptibility-inducing effects of testosterone. We hypothesize that each hormone will act through a subset of the proposed mechanisms. We hope to identify immune mechanisms that are specifically modulated by each. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MOLECULAR CHARACTERIZATION OF GNRH RECEPTORS Principal Investigator & Institution: Kakar, Sham S.; Associate Professor; Medicine; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2001; Project Start 15-JUL-1993; Project End 31-JAN-2002

Studies

37

Summary: (adapted from the applicants abstract) Gonadotropin releasing hormone (GnRH), through its G-protein -coupled, high-affinity receptor located on gonadotropes of the anterior pituitary, stimulates the secretion of gonadotropins (LH and FSH). It is now known that GnRH receptors (GnRHR) are also present in extra pituitary tissues, hormone-responsive tumors and tumors derived cell lines, suggesting that GnRH may serve additional functions. GnRHR expression is highly regulated in exhibiting both up and down regulation by its cognate ligand, by gonadal steroids and peptides. However, the mechanisms involved in altering the rate of expression of the GnRHR at molecular levels is unknown. In order to understand the regulation of GnRHR gene expression in the pituitary, extra-pituitary tissues and hormone responsive tumors, the PI isolated the human GnRHR gene and defined its genomic organization. The human GnRHR gene is composed of two introns and three exons, and spans over 20 kb. It contains multiple transcriptional initiation sites and a large number of putative regulatory sequences for various hormones and other regulatory factors raising the possibility of tightlyregulated, differential expression of the receptor gene, which may be tissue specific. Thus the GnRHR may play a key role in the regulation of hormone-responsive tumors growth and its responsiveness to various stimuli and/or it's expression may be regulated by such stimuli. The long termed goals are to understand at the molecular level the DNA components and transcriptional factors that are responsible for the tissue specific expression and hormonal regulation of the human GnRHR gene, and to define the molecular mechanism of inhibition of tumor cell growth by GnRH. The specific aims are: 1) To characterize the promoter sequence for GnRH-receptor gene in pituitary, extra-pituitary tissue and in hormone responsive tumors, 2) To study GnRHR, transcriptional regulation by estrogen, progesterone, glucocorticoid, testosterone, GnRH, inhibin, TPA and cAMP, 3) To identify the cells in tumors expressing GnRH receptor using a monoclonal antibody, and 4) To determine the expression of GnRH and GnRHR in normal and tumor tissues. These studies will likely provide a greater understanding of the regulation of the GnRH-receptor gene and allow us to better understand the complex mechanism of its transcriptional regulation. These studies have the potential to provide the basis for the development of a new class of drugs for treatments of hormone-responsive tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR CONTROL OF MALE REPRODUCTION Principal Investigator & Institution: Good, Deborah J.; Veterinary and Animal Sciences; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Although over 16 different hypothalamic transcription factors are implicated in controlling fertility, the molecular mechanisms of reproduction remain unclear. The hlh2 basic helix-loop-helix (bHLH) transcription factor is expressed throughout the developing nervous system. In adults, expression is limited to specific neurons in the hypothalamus, pre-optic area and hebenula. Nhlh2 knockout mice (N2KO) are obese and hypogonadal. In addition, they have reduced levels of follicle stimulating hormone and testosterone, and do not show normal male sexual behaviors. N2KO mice also have reduced sperm concentration in their caudal epididymus, but using in vitro fertilization, we have found that sperm from N2KO mice are fully capable of fertilizing oocytes. Thus, infertility in male N2KO mice is largely due to lack of sexual behavior and partially due to reduced sperm production. In other studies, we have found that levels of two neuropeptide processing enzymes, PC1 and PC2, are reduced up to 90% in N2KO mice. These processing enzymes are thought to

38

Testosterone

process GnRH as well as other hypothalamic neuropeptides involved in both fertility and obesity. Based on these preliminary findings, we propose that the Nhlh2 transcription factor regulates male sexual behavior and fertility by up-regulating the expression of PC1and PC2 processing enzymes which are necessary for production of mature GnRH peptide in the pre-optic area of the brain. We will use both animal-based and molecular approaches to test this hypothesis. In the first aim, we will ask if Nhlh2 is co-expressed with GnRH, PC1 and PC2. We will also measure levels of PC1 and PC2 mRNA in pre-optic area neurons, and levels of mature GnRH peptide in N2KO and normal mice. In the second aim, we will supply male N2KO mice with testosterone and ask if this hormone is sufficient to restore male sexual behavior and spermatogenesis. To date, N2KO mice are the only knockout mice in which deletion of a neuronal bHLH transcription factor results in obesity, hypogonadism, and lack of male sexual behavior. Studies of these animals are key to understanding molecular control of male fertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR EPIDEMIOLOGY OF PROSTATE CANCER Principal Investigator & Institution: Rebbeck, Timothy R.; Associate Professor; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Prostate cancer is the most commonly occurring cancer in U.S. men. African American men have the highest prostate cancer rate in the world. There is relatively little information available about the etiologic factors that may explain these rates. The objective of the present study is to examine the role of genes that regulate the disposition of testosterone in prostate cancer etiology, and to evaluate whether these genes explain, in part, differences in prostate cancer rates between African Americans and U.S. Caucasians. These genes include the cytochromes P450 CYP3A4 and CYP19, 5alpha-reductase II (SRD5A2), androgen receptor (AR), and the type II 3beta-hydroxysteroid dehydrogenase (HSD3beta2). All of these genes are involved in the downstream metabolism of testosterone, and thus focus our hypotheses on a relevant, defined set of metabolic pathways. Three specific aims are proposed here. In Specific Aim 1, we will systematically evaluate allelic and genotypic distributions at these candidate genes, and compare these distributions in four ethnic groups (Ghanaian, Senegalese, African American, and US Caucasian men). In addition, obtaining data from Ghana and Senegal will initiate collaborations to foster formal studies of prostate cancer etiology in Africans. In Specific Aim 2, we propose to undertake both case-case and case-control analyses to evaluate the relationship of candidate genotypes with prostate cancer in African Americans. In Specific Aim 3, we propose to evaluate differences in the genotype-prostate cancer relationship between African Americans and Caucasians. We will again use case-case and case-control designs to evaluate differences in prostate cancer etiology between these two groups. In order to address these hypotheses, we will undertake a study using an existing subject accrual system to identify a sample of 800 incident prostate cancer cases and 800 controls. Half of these will be African American and half will be Caucasian. A sample of healthy Ghanaian and Senegalese controls will also be accrued. Risk factor information will be obtained from a questionnaire interview, a biosample containing DNA will be collected using a non-invasive cheek swab method, and pathology information will be collected using a standardized medical record abstraction approach. An understanding of the complex interplay of genetic variability at multiple loci and of environmental agents may improve our understanding of

Studies

39

prostate cancer etiology and risk prediction. This information could then be used to more effectively apply prostate cancer prevention and control strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR EPIDEMIOLOGY OF TESTICULAR CARCINOMA Principal Investigator & Institution: Schwartz, Stephen Marc.; Full Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (Adapted from the Applicant's Abstract): The incidence of testicular germ cell carcinoma (TGCC), the most common malignancy developing in young men, has increased several-fold since the 1950s. Despite three decades of research in human populations, the etiology of TGCC remains obscure and our knowledge of risk factors is limited largely to demographic characteristics and a history of undescended testes. Clinical, non-human experimental, and epidemiologic studies of TGCC have provided evidence that exposure to abnormal levels of steroid hormones, either in utero, perinatally, and/or early in life, may be a key etiologic factor for TGCC. Epidemiologic support of this hypothesis, however, has been inconsistent, a phenomena attributable at least in part to the limited ability of interview and medical record data to capture the relevant exposures. Recent progress in identifying polymorphisms in genes contributing to endogenous steroid hormone metabolism presents an opportunity to expand beyond the scope of prior epidemiologic studies by addressing the hypothesized hormonal etiology of TGCC at the molecular genetic level. Specifically, we propose to test the hypothesis that inherited variation in genes involved in stimulating testicular steroidogenesis, synthesizing and metabolizing testosterone, and androgen signaling, is related to the risk of developing TGCC. A population-based case-control study will be conducted. Cases will be approximately 280 incident cases of TGCC diagnosed between October 1998 and September 2003 and who are residents of a three county metropolitan region in western Washington State. Demographically similar controls (n=840) will be ascertained from the general population using random digit telephone dialing. Cases and controls will be interviewed in-person regarding medical and lifestyle histories. A venous blood sample will be obtained from all consenting participants and peripheral leukocytes isolated and stored. Genomic DNA extracted from leukocytes will be tested for variants in the following genes involved in 1) the stimulation of testicular steroidogenesis (Luteinizing Hormone and Insulin-Like Growth Factor-1), 2) the synthesis and metabolism of testosterone (Cytochrome p450 11a [CYP11a], CYP17, 3Beta-Hydroxysteroid Dehydrogenase Type II, CYP3A4, and UDPGlucuronosyltransferase 2B15), and 3) testosterone signaling (Androgen Receptor). Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes and alleles for each gene. The sample size also will provide sufficient statistical power to identify interaction between high-risk genotypes. The findings from this study therefore will add new information regarding the epidemiology and etiology of TGCC, and will serve as a resource for future investigations of genetic associations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NEUROENDOCRINE GENES GOVERNING REPRODUCTION Principal Investigator & Institution: Steiner, Robert A.; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAR-2006

40

Testosterone

Summary: Reproduction in males is governed by hormonal communication linking the brain and the testis. The brain integrates cues from the environment and hormonal signals from the testis to govern the secretion of gonadotropin-releasing hormone (GnRH) from neurons in the forebrain and hypothalamus. GnRH directs the synthesis and release of the gonadotropins, LH and FSH, which exert control over testicular function. Testosterone from the testis then acts on the brain to provide the primary signal to regulate sexual differentiation, gonadotropin secretion, gender identity, and libido. Androgens, including testosterone and related compounds, are being used for male contraception, as well as the treatment of delayed puberty, use will continue to growth-as well the demand for more accurate information about their actions on the brain. The primary objective of this research is to discover the molecular and cellular basis of testosterone's action in the forebrain of the male macaque, a primate whose reproductive physiology closely resembles that of man. The specific aims of this project are focused on learning more about the role of 4 particular neuropeptides and amphetamine- regulated transcript (CART), agouti-related protein (AgRP), melaninconcentrating hormone (MCH), and galanin-like peptide (GALP) in the control of gonadotropin secretion and as molecular targets for the action of testosterone and other related androgens on the brain. Using systems, cellular, and molecular biological techniques, we will examine the effects of these neuropeptides on LH secretion, test the hypothesis that the genes coding for the peptides are targets for androgen regulation, identify the mechanisms involved in signal transduction, and begin to map the synaptic circuitry linking these particular molecules to GnRH neurons. Understanding the cellular and molecular actions of androgens in the brain of a primate, whose reproductive physiology is similar to humans, is the first step toward the goal of putting androgenic compounds into use that have maximum therapeutic benefits with minimal deleterious side effects. Over time, the knowledge provided by these studies will be an aide to the development of improved strategies for addressing the problems of overpopulation, increasing option for family planning, and treating disorders of reproduction in men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NONGENOMIC ANDROGEN SIGNALING IN SERTOLI CELLS Principal Investigator & Institution: Walker, William H.; Cell Biology and Physiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 09-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Testosterone is absolutely essential for spermatogenesis and targets Sertoli cells in the mammalian testis through the androgen receptor (AR) to produce factors required for germ cell development and survival. We now have evidence for an alternative, rapid (< 5 min) mechanism by which testosterone stimulates the phosphorylation (activation) of the Erk MAP kinase and the CREB transcription factor in primary rat Sertoli cells. This novel mechanism of testosterone action will impact a broad number of processes in Sertoli cells because MAP kinase and CREB are focal points for the control of numerous signaling pathways. Furthermore, this proposal addresses a longstanding gap in the understanding of the mechanisms by which testosterone regulates spermatogenesis as few AR-regulated genes have been identified. We will test the overall hypothesis that testosterone binding to AR activates a Src kinase and/or Ca2+-mediated signaling cascade resulting in the phosphorylation and activation of MAP kinase and CREB. Aim 1 is to test the hypothesis that AR is required to mediate the rapid phosphorylation of MAP kinase and CREB. Androgeninduced ERK and CREB phosphorylation will be assayed in normal and AR deficient rat

Studies

41

primary Sertoli cells. AR domains required for androgen signaling will be identified. The hypothesis that populations of AR are associated with the Sertoli cell plasma membrane will be tested. Aim 2 is to test the hypothesis that androgen activates MAP kinase and CREB by a Src kinase-regulated pathway and/or via a Ca2+-mediated pathway. Androgen-induced Src kinase activity will be determined and androgenactivation of Erk and CREB wilt be assayed after addition of pharmacological and genebased inhibitors of Src activity. Specific blockers of Ca2+ channels and Ca2+ actions will be used to test the hypothesis that Ca2+-mediated signaling pathways propagate androgen signals. Aim 3 is to test the hypothesis that androgen activates CREB and MAP kinase-regulated gene expression. Androgen regulation of MAP kinase and CREBmediated gene expression will be tested using reporter plasmids in transient transfection assays. The regulation of specific endogenous Sertoli cell target genes via CREB will be assessed using RNAse protection assays. The information generated from this study will be directly applicable to divining the mechanisms by which testosterone supports spermatogenesis and maintains male fertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOCICEPTION

NORADRENERGIC

MODULATION

OF

TRIGEMINAL

Principal Investigator & Institution: Mokha, Sukhbir S.; Professor; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: The long-term objective of the proposed research is to enhance our understanding of pain mechanisms and their control in the dorsal horn of the medulla (trigeminal nucleus caudalis), a region closely associated with many clinical pain conditions such as migraine, toothache, trigeminal neuralgia and temporomandibular joint related disorders. Specifically, the proposed research will elucidate the sex-related differences in the control ofnociceptive information originating from oro-facial tissues particularly the tooth pulp. The specific aims of the investigation are to determine that, a) activation of alpha2-adrenoceptors (alpha2-ARs) and descending noradrenergic pathway from the Kolliker Fuse nucleus (KF = A7) produce sex-specific modulation of trigeminal nociception through the participation of gonadal steroids, and b) the sexspecific modulation is mediated by gonadal hormone-induced, particularly estrogeninduced, genomic and non-genomic mechanisms The proposed studies will be carried out using electrophysiological, behavioral, molecular (in-situ hybridization) and cellular (in-vitro intracellular) techniques in male, proestrous female, ovariectomized, estradiol treated ovariectomized females, castrated males, testosterone treated castrated males and sham operated animals. Single unit activity of tooth pulp specific (TPS), nociceptive specific (NS) and wide dynamic range (WDR) neurons including trigeminothalamic neurons will be recorded in the superficial and deeper dorsal horn of the medulla in anesthetized male and female rats. Effects of microiontophoretically applied alpha2-AR agonists and antagonists will be tested on the responses evoked by, a) electrical stimulation of the tooth pulp, b) noxious stimuli, and c) activation of N-methyl-Daspartic acid (NMDA) receptors. Nociceptive scratching behavior will be elicited by microinjection of NMDA through a cannula implanted dorsal to the medullary dorsal horn. Effects of alpha2-AR agonists and antagonists microinjected through the same cannula, and stimulation in KF will be investigated on the NMDA-induced nociceptive scratching behavior in males and females. Contribution of gonadal steroid-induced genomic and non-genomic changes in generating sex-related differences will be investigated by examining whether, a) estrogen and testosterone alter the expression of

42

Testosterone

the alpha2A-AR gone in the dorsal horn of the medulla, b) the estrogen receptor is colocalized in alpha2A-AR containing neurons, and c) estrogen alters the coupling of alpha2-ARs to potassium channels. The proposed studies will deepen our understanding of sex-related differences in the modulation of trigeminal nociception and lead to the development of better pain control strategies in males and females. The new information may also help in the development of analgesics that are free of the abuse potential and side effects associated with narcotics such as morphine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANOMALIES

ORGANOCHLORINE

PESTICIDES

AND

MALE

GENITAL

Principal Investigator & Institution: Bhatia, Rajiv; Public Health Institute 555 12Th St, 10Th Fl Oakland, Ca 94607 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: DDT, one of the most ubiquitous of a class of endocrine disrupting chemicals, has been associated with dramatic adverse effects on the reproductive systems of animals. Effects of DDT in animals and experimental systems are observed at levels in the range of human exposure. Chemicals having endocrine activity similar to DDT are currently in use, and recent studies have suggested male reproductive system disorders are becoming more prevalent. The Investigators propose a nested case-control study of cryptorchidism and hypospadias and in utero exposure to DDT within the Child Health and Development Studies (CHDS) cohort. Such an examination of the role of DDT in the causation of human genital anomalies has not been done previously. The CHDS, a longitudinal study of 20,000 pregnancies among Northern California Kaiser Foundation Health Plan members, enrolled subjects between 1959 and 1966 a time of high domestic use of DDT. All subjects were interviewed during pregnancy about habits and sociodemographic characteristics and almost all children were followed for the first five years of life. The subjects will include 155 male liveborn infants with hypospadias or cryptorchidism and an equal number of randomly selected controls. Levels of DDT and its major metabolites will be assayed from maternal serum currently stored at the National Institutes of Health. The sex steroid hormone, testosterone, and sex hormone binding globulin, possible markers for reproductive system effects of DDT, will be measured from cord blood samples in a subset of 50 infants. The authors hypothesize that maternal DDT levels will be higher in mothers of male with genital anomalies after controlling for confounders. They will examine th effect of DDT on birth weight, gestational age, and steroid hormones as well as the roles these factors may play in the mechanism of DDT's effects. Finding DD to be a risk factor for male genital malformations, would suggest endocrine disrupting chemicals may be significant causes of male reproductive disorders and potentially causes of cancers of the male and female reproductive systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN FAILURE IN LH/HCG RECEPTOR KNOCKOUT ANIMALS Principal Investigator & Institution: Rao, Ch V.; Professor and Director; Obstetrics and Gynecology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: Both IIpo Huhtaniemi's and our group recently succeeded in generating LH receptor knockout mice by gene targeting in embryonic stem cells. Although this gene

Studies

43

knockout was not lethal, it rendered animals infertile. While ovaries of wild- type and heterozygous animals contained LH receptors, ovaries of homozygous littermates contained none. Also, while ovaries of wild-type and heterozygous animals were normal in size and contained preovulatory follicles and corpora lutea, the ovaries of homozygous littermates were small and pale with an arrest of follicular growth at the antral stage. Preliminary studies indicated this arrest could, at least partly, be due to a decrease in telomerase levels and a consequent increase in apoptosis. In homozygous animals, LH levels were markedly elevated, FSH levels were moderately elevated, and estradiol and progesterone levels decreased but were not totally suppressed. Knockout animals can be extremely useful in answering a number of unknowns in LH biology. For example, we could learn: 1) whether LH actions are required for the presence of normal numbers of primordial, primary, preantral and antral follicles; 2) whether FSH can induce follicular growth and ovulation in the total absence of LH actions; 3) what role LH signaling plays in ovarian development and function from one week after birth through one year of age; 4) what ovarian actions of LH are mediated by estradiol, progesterone and testosterone; 5) identify and characterize previously unidentified ovarian genes that are regulated by estradiol, progesterone, testosterone, LH or by their combination; and 6) whether using gene therapy to introduce LH receptors into ovaries of null animals makes them cyclic and ovulate but still not get pregnant because they do not have LH receptors in the uterus. These are only a few examples of how the use of null animals could advance our current understanding on the role of LH in different ovarian functions. We propose three specific aims in this application: 1) Investigate structural and functional defects in ovaries of 7-day, 25-day, 60-day and 1-year old null mice to compare with their age- matched, wild-type and heterozygous siblings. 2) Investigate whether estradiol, progesterone and testosterone replacement therapy can correct structural and functional defects in ovaries of LH receptor knockout animals. 3) Determine whether retroviral mediated LH receptor gene transfer can correct structural and functional defects in ovaries of null animals so they become cyclic and ovulate even though pregnancy may not occur due to the absence of LH receptors in the uterus. There are several strengths in this proposal. Foremost is studying LH biology using knockout technology. Second is using steroid hormone replacement and gene therapies. Third is using cDNA expression arrays, a powerful technique in gene expression analysis. All techniques to be used in the proposed studies have already been established to obtain preliminary data presented in the proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: P4: SEX DIFFERENCES IN CRF, NORADRENERGIC FUNCTION AND OXYTOCIN IN CATS WITH IC Principal Investigator & Institution: Buffington, Charles A.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The long-term goal is to exploit a naturally occurring bladder disease in domestic cats (Feline Interstitial Cystitis - FIC) to gain a better understanding of a painful bladder disorder in humans called interstitial cystitis (IC), and by extension other pelvic pain syndromes. This is because many patients with IC also have IBS and other neurovisceral disorders that predominantly affect women, and appear to be exacerbated by stress. The studies proposed here are designed to further investigate the causes of these neurological alterations in controlled studies of cats diagnosed with IC and healthy cats. The studies are needed to elucidate the significance of the underlying neurological abnormalities present in human patients with IC. They also are intended to

44

Testosterone

guide the choice of subsequent studies toward the primary systems involved in IC, with the eventual goal of identifying rational treatments of IC in human beings. The overall objective of this proposal is to test the hypothesis that interactions between CRF, sex hormones and the alpha-2 adrenoceptor (alpha2-AR) play a role in the sex difference in stress-responsiveness of cats with FIC. The rationale for the proposal is based on 1) clinical evidence that females are more prone to develop IC than males (intact males in cats), 2) the gap in knowledge in factors that may account for such sex differences due to the paucity of experimental data in this field, 3) evidence from our recent studies pointing to a role of alpha2-AR dysfunction in cats with IC, and 4) existing evidence that urothelial and alpha2-AR function can be modulated by testosterone, estrogen, and oxytocin. By studying a natural occurring animal model of IC which shares many features with a rat model of IBS, and with the respective human patient populations, we will be able to assess the role of sex hormones on the expression of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSIOLOGIC TESTOSTERONE REPLACEMENT IN WOMEN Principal Investigator & Institution: Friedman, Theodore C.; Assistant Professor; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, Ca 90059 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: In women, the effects of androgen deficiency have not been well studied, but likely include decrease in quality of life, poor libido, altered body composition and osteopenia. In a recent double-blind, placebo-control study treating oopherectomized women with transdermal testosterone, higher doses of testosterone supplementation resulted in an improvement in sexual function and psychological well-being. Little side effects were noted. Since both the adrenals and the ovaries contribute to testosterone product in normal women, patients with hypopituitarism are likely to have severely diminished androgen production from both sources. In fact, a recent study demonstrated very low levels of total and free testosterone as well as the androgen precursors, DHEAS, DHEA, and androstenedione in women with hypopituitarism. Although women with hypopituitarism often have decreased libido, altered body composition and impaired quality of life, symptoms possibly related to androgen deficiency, the effects of testosterone replacement in these women have not been studied. In the current proposal, we will test the hypothesis that female patients with hypopituitarism will benefit from physiological testosterone replacement in terms of objective and subjective sexual function, cognitive function, muscle size and physical performance and body composition. Female patients (ages 18 to 50 years) with testosterone deficiency secondary to hypopimitarism will receive either placebo or transdermal testosterone gel (2 mg of testosterone/day, leading to a targeted serum testosterone in the upper range of normal) in a double-blind study of 4 month duration. Potential side effects will be monitored. We expect this study will accurately assess the benefits and deleterious effects of physiological testosterone replacement in women with hypopituitarism. At the conclusion of this study, we expect to determine if testosterone will be added to the standard hormonal replacement for women with hypopituitarism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PHYSIOLOGY OF PUBERTY AND ANTISOCIAL BEHAVIOR Principal Investigator & Institution: Susman, Elizabeth J.; Shibley Professor; Biobehavioral Health; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802

Studies

45

Timing: Fiscal Year 2001; Project Start 21-FEB-2001; Project End 31-JAN-2004 Summary: Applicant's The proposed study integrates for the first time the biological components of puberty with the study of antisocial behavior in a longitudinal examination of hormones, psychological attributes, physical maturation and parent characteristics in 7-, 9-, and 11-year-old girls and boys. The importance of the study is derived from the recent statistics showing that the overall crime rate is down but rates in youth continue to increase (United States, Department of Justice, 1999). Past studies have virtually ignored biological processes and the course of antisocial behavior. Even when biosocial processes in antisocial behavior are considered, females tend not to be included. The specific aims are: (1) to identify the relationship between increases in adrenal androgens and testosterone and increases in antisocial behavior during puberty (2) to establish the effect of gonadal and adrenal hormones, affective symptoms, exposure to violence, peer interactions and parenting on antisocial behavior, (3) to assess the effect of antisocial behavior, affective symptoms, exposure to violence and family functioning on adrenal androgens, testosterone and cortisol and (4) to assess the effect of earlier and later timing of puberty on antisocial behavior and to examine the effects of the interactions between risks for antisocial behavior and timing of puberty on antisocial behavior. Constructs in the model are: Child Risk Attributes (hormones, affective expression, exposure to violence), Timing of Puberty, Parent Risk Attributes (discipline and supervision) and Sex. The participants will consist of a random sample of 400, 7-,9-, and 11-year-old African American and White children and adolescents randomly selected from Allegheny County, PA. The design consists of a cross-sequential (accelerated) longitudinal design with three cohorts followed at 9-month intervals for 4 times of measurement. The study will fill a major void in the literature as it aims to assess both the effect of hormones on behavior and the neurobiological effect of antisocial behavior on hormone concentrations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT -- EFFECTS OF MERCURIC CHLORIDE ON MALE REPRODUCTION Principal Investigator & Institution: Atkinson, Alfonza W.; Tuskegee University Tuskegee Institute, Al 36088 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 31-MAY-2008 Summary: Abstract: Effects of mercuric chloride (MC) on the reproductive performance of two successive generations of rats were evaluated in our laboratory. Significant differences resulting from exposure of the F0 generations to MC were found in implantation efficiency, fertility, live births, day 4 survival indices, litter size, and body weights of F1 pups. Limitations of this study design were its inability to determine which sex, male, female or both, may have contributed most to the reproductive and fertility effects, and the lack of a detailed semen evaluation that is critical in the assessment of the male reproductive system after exposure to environmental toxicants. In order to determine which sex was responsible for adverse effects on reproduction, a crossover mating trial is planned with the control and high dose groups. The long-term goals of the research proposed here are to 1. Test the hypothesis that reduced fertility seen in the F0 generation of the study by Atkinson et al 2001 results from exposure of male rats to MC. 2. Test the hypothesis that MC-induced reduced fertility may have resulted from deficits in epididymal sperm function (number, morphology and motility) and/or lower testosterone. 3. Test the hypothesis that MC-induced decreased testicular weights and serum testosterone levels may have resulted from increased apoptosis in germ and/or somatic cells.

46

Testosterone

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYCYSTIC ADOLESCENTS

OVARIAN

SYNDROME

IN

OVERWEIGHT

Principal Investigator & Institution: Hoeger, Kathleen M.; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Polycystic Overy Syndrome (PCOS) is a broadspectrum disease characterized by chronic anovulation and androgen excess, affecting 48% of women. Onset of the disorder is recognized to occur around the time of puberty but is often not diagnosed until adulthood. More than half of women with PCOS are obese, and insulin resistance appears to be an important part of its underlying pathophysiology. Long-term consequences in PCOS are now recognized to include increased risk of development of type 2 diabetes mellitus and cardiovascular disease. This has led to an interest in reduction of insulin resistance as a long-term treatment strategy. This reduction in insulin resistance can be accomplished by weight reduction or by insulin sensitizers such as metformin. To date, however, there are limited data on the effectiveness of insulin sensitizers and no data on the impact of weight reduction in adolescents with PCOS. Adolescence is a time of tremendous physical and psychosocial change. Obesity in adolescence is often predictive of lifelong obesity. The constellation of hirsutism, irregular bleeding, and obesity, often seen in adolescents with PCOS, could potentially have lifelong social and health consequences. A successful weight reduction strategy with improvement in insulin sensitivity at the onset of the symptoms of PCOS could have substantial long-term health benefits. The applicant hypothesizes that weight loss and metformin in the overweight adolescent with PCOS can reduce insulin resistance and improve the symptoms and metabolic profile associated with PCOS. Accordingly, a randomized, placebo-controlled, parallel-group trial comparing metformin and intensive lifestyle modification is proposed to gather preliminary data on the rate of ovulation, changes in testosterone and insulin and impact on cardiovascular risk of weight reduction and metformin as compared to placebo in a total of 30 subjects. Data obtained from this pilot trial on recruitment rates, drop-out, compliance, and estimated treatment effect sizes will be used to refine power calculations for a large-scale randomized trial focused on a comparison of metformin and weight reduction in obese adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYMORPHISMS IN PROSTATE CANCER CARCINOGENESIS Principal Investigator & Institution: Everson, Richard; Internal Medicine; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 23-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract): Incidence and mortality rates for prostate cancer among African-American men in Detroit are among the highest in the world. The extraordinary impact of this disease on our community has led to the development of several large NIH funded research studies of prostate cancer. Two of these studies focus on the etiology of prostate cancer. One, a study of the frequency and extent of prostatic intraepithelial neoplasia and latent prostate cancer at autopsy of sudden death victims, documents frequencies of the earliest microscopic precursors of prostate cancer. The second, a population-based case-control study, characterizes determinants of clinical disease. The autopsy study includes over 600 subjects cases and

Studies

47

the case-control study over 700 cases and an equivalent number of controls. Both include a high proportion of African-American men. Although extensive, these studies do not address the role of genetic susceptibility in the etiology of prostate cancer. Recent studies reporting associations between genetic polymorphisms and prostate cancer risk provide important opportunities for determining the etiology of prostate cancer using the data and tissue resources from our ongoing studies. The polymorphisms include factors governing the biological effects of androgens, (polymorphisms in the androgen receptor gene itself and enzymes determining the synthesis and degradation of active forms of testosterone) and the biological effectiveness of vitamin D (polymorphisms in the receptor). Analysis of specimens from our ongoing studies will allow investigations of the impact of these polymorphisms on both the earliest detectable phase of prostate cancer in the autopsy study and its progression to clinical disease in the case-control study. Our analysis will emphasize comparisons of findings for African-American and Caucasian males from the same community. This project will provide a valuable opportunity to define the role of the individual effects and the interplay of androgens, vitamin D, and race in the etiology of prostate cancer, and to distinguish their effects on its preclinical initiation and progression to clinical disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREGNANCY AND SEXUAL DIFFERENTIATION OF THE FETAL BRAIN Principal Investigator & Institution: Gorski, Roger A.; Professor of Neurobiology; Brain Research Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 06-JUN-2001; Project End 31-MAY-2003 Summary: (provided by applicant) Sexual differentiation of the brain in male mammals is dependent upon testicular production of testosterone (T). In the laboratory rat this process occurs perinatally. A surge of T on embryonic days 18/19 appears to sensitize the hypothalamus to exposure of T postnatally. The mechanism of action of this embryonic surge of T and its regulation are basically unknown. With respect to the latter, there is some evidence that at least the earliest secretion of T by the Leydig cells of the testes is independent of other factors and is possibly programmed genetically. However, even "programmed" genetic events are subject to modification. The objective of the present study is to determine whether or not the maternal hormonal environment plays any role in the prenatal events which lead eventually to the sexual differentiation of the brain. Pregnant female rats will be hypophysectomized on embryonic day 13, or sham hypophysectomized. In an attempt to identify purely fetal/maternal interactions, half the male and female pups will be gonadectomized on the day of birth or sham gonadectomized. At 50 days of age the experimental rats will be sacrificed and their brains removed and processed histologically. The volume of the sexual dimorphic nucleus of the preoptic area (SDN-POA), which is normally greater in the male rat, and that of the anteroventral periventricular nucleus (AVPV), which is normally greater in the female rat, will be determined. It is hypothesized that hypophysectomy of the pregnant female will inhibit the development of the SDN-POA in males but increase AVPV volume. Potential effects on the female are more difficult to predict because there is evidence both for the hormoneindependent development of the female rat brain and its dependence on some exposure to gonadal hormones. The demonstration of a maternal contribution to the sexual differentiation of the fetal brain would be of considerable importance to our understanding of the fundamental concept of the sexual differentiation of the brain in mammal presumably including human beings.

48

Testosterone

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRENATAL NEUROENDOCRINE MEDIATORS OF YOUNG ADULT SMOKING Principal Investigator & Institution: Niaura, Raymond S.; Director of Research; Miriam Hospital Providence, Ri 02906 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Maternal smoking during pregnancy (MSDP) has been linked to significantly increased risk for offspring smoking uptake. Given high societal costs of smoking, and risk for transgenerational transmission of offspring smoking, elucidating mechanisms underlying the MSDP-offspring smoking link is critical for intervention and prevention efforts. Acknowledging the possibility that confounding factors (e.g., genetic influences, maternal psychiatric comorbidities) may also underlie the MSDP-offspring smoking link, we follow up on one potential mechanism shown previously by Kandel and Udry l to influence smoking uptake in offspring of smoking mothers. In the only study to examine mechanisms underlying the MSDP-offspring smoking link, Kandel and Udry found that increased maternal testosterone levels during pregnancy were associated with increased risk for smoking uptake in female offspring. In the proposed study, we have an unprecedented opportunity to expand on Kandel and Udry's findings by examining two maternal hormones (testosterone and cortisol) during pregnancy as mediators of links between MSDP and offspring symptoms of nicotine dependence in both males and females using offspring from the Providence Cohort of the National Collaborative Perinatal Project (NCPP). Six hundred ninety-three adult offspring from the Providence cohort of the NCPP will be included in the study. Maternal smoking was previously assessed prospectively as part of the original NCPP battery. Symptoms of nicotine dependence in offspring were also assessed through a follow-up study of the original NCPP cohort. Maternal sera from three trimesters of pregnancy are accessible through collaboration with NIH personnel. Funding for this proposal will allow us to assay maternal sera for testosterone (and its binding protein) and cortisol (and its binding protein) as well as cotinine (a nicotine metabolite). A series of regression analyses will then be utilized to test our hypotheses regarding maternal levels of free testosterone and free cortisol as mediators of links between MSDP and offspring symptoms of nicotine dependence (measured by self-report and maternal cotinine levels) in both males and females. Identification of mechanisms underlying the MSDP-offspring smoking link may lead to targeted intervention and prevention efforts in pregnant smokers and high-risk offspring. Further, elucidating mechanisms underlying the MSDPoffspring smoking link will also represent a first step toward preventing the transmission of MSDP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PRIAPISM IN BOYS AND YOUNG MEN: INCIDENCE AND PREVALENCE Principal Investigator & Institution: Redding-Lallinger, Rupa C.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: The primary goal of this study is to conduct a comprehensive investigation of priapism in boys and young men with sickle cell disease (SCD). As such, it represents the initial step toward defining an effective way to manage priapism, and to reduce the frequency of impotence that is its major complication in adult males with SCD. The aims

Studies

49

of this proposal are: 1) to conduct a Iongitudinal cohort study in order to define the incidence of priapism in relationship to the physical and hormonal developmental stages of puberty and early maturity, to explore the relationship between priapism and psychological adjustment; and 2) to conduct a pilot, placebo-controlled intervention trial in which the ability of pseudoephedrine to prevent priapism will be evaluated. The first stage of this proposal involves an observational study that will be open to all boys and young men with SCD between the ages of 7 -29 years. They will keep daily records of the occurrence of priapism, and will be admitted every 6 months for an intensive evaluation of physical growth, genital pubertal stage, body composition, bone age, gonadotropins, testosterone, insulin-like growth factor and nocturnal penile tumescence. During these admissions, the participants will also complete several psychological assessments. Data from this phase will be used to identify the association (if any) between priapism and pubertal stage, gonadotropin levels, and testosterone concentration. The data will also determine if there is a relationship between priapism and psychological adjustment. The second stage of this proposal will seek to enroll those individuals who are found to have qualifying episodes of priapism on to a randomized, double-blinded, placebo-controlled clinical trial of pseudoephedrine. The purpose of this pilot study is to determine whether pseudoephedrine is able to prevent episodes of priapism. During this trial, each participant will continue to keep the same daily journal. In addition, each participant will be admitted at the beginning and end of the trial to complete the same physical, hormonal and psychological assessments as were performed in the observational phase. The outcome measures of the prevention trial will be the occurrence of priapism, duration of priapism and the interval between episodes of priapism. In addition, physical growth, secondary sexual development, body composition and psychological adjustment will be compared between the treatment arms. The data collected will establish the feasibility of certain key methods, and will provide estimates of rates, standard deviations, median time-to-event. These results, which are absolutely essential before a large scale treatment trial can be planned, will provide the biological and statistical background for future work in this field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTATE CANCER IN SENEGALESE MEN Principal Investigator & Institution: Gueye, Serigne M.; Hopital General De Grand Yoff Dakar Bp-3270, Senegal Dakar, Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Prostate cancer is the most commonly occurring cancer in men of African descent in the US. Even though African American men have the highest prostate cancer rate in the world, there is relatively little information available about the etiologic factors that may explain these rates. Despite the knowledge that prostate cancer occurs at high rates in men of African descent in the Americas, very little data is available regarding the epidemiology of prostate cancer in native African men, even though prostate cancer seems to be prevalent in that population. The objective of the present study is to examine the role of genes that regulate the disposition of testosterone in prostate cancer etiology, and to evaluate whether these genes explain, in part, ethnic differences in prostate cancer rates. These genes include the cytochromes P450, CYP3A4 and CYP19, 5alpha-reductase II (SRD5A2), androgen receptor (AR), and the type II 3beta-hydroxy-steroid dehydrogenase (HSD3b2). All of these genes are involved in the downstream metabolism of testosterone, and thus focus our hypotheses on a relevant, defined set of metabolic pathways. The primary goals of this application are to 1) develop prostate cancer research infrastructure in Senegal, and

50

Testosterone

2) test feasibility of data collection for use in future studies of prostate cancer in West Africa. Three specific aims are proposed here to focus these goals. In Specific Aim 1, we will undertake multi-ethnic genotype to evaluate differences in the distribution of candidate genotypes in Senegales, US Caucasian, and African American controls. In Specific Aim 2, we will develop a hospital-based prostate tumor registry at the Hopital General de Grand Yoff in Dakar, and describe the prostate cancer cases diagnosed at this hospital over a three-year period. Finally, in Specific Aim 3, we propose to evaluate whether there is a relationship between candidate genotypes and characteristics of prostate tumors in Senegalese men using a case-case study design, and compare these results with African American and US Caucasian men. In order to address these specific aims, we will identify a sample of incident prostate cancer cases and controls from Senegal, and make comparisons among these groups. Risk factor information will be obtained from a questionnaire interview, a biosample containing DNA will be collected using a non-invasive cheek swab method, and pathology information will be collected using a standardized medical record abstraction approach. The information collected in Dakar will be compared against an ongoing study of prostate cancer in US Caucasian and African American men ("Molecular Epidemiology of Prostate Cancer", funded by R01-CA85074, Timothy Rebbeck, Principal Investigator). The resources and data generated through this application will be used to establish additional studies of prostate cancer and potentially other cancers in Senegal including molecular epidemiological case-control studies of prostate cancer etiology. An understanding of the complex interplay of genetic variability at multiple loci and of environmental agents may improve our understanding of ethnic differences in prostate cancer etiology and risk prediction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTATE CANCER: IMPACT OF FAT & FLAXSEED MODIFIED DIET Principal Investigator & Institution: Demark-Wahnefried, Wendy; Associate Professor; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 04-JAN-2002; Project End 31-DEC-2005 Summary: Diet is presumed to play a major role in prostate cancer - a leading cancer among American men. Yet, to date there are no dietary interventions with proven efficacy for either prevention or complementary care. The proposed study will focus on flaxseed supplementation (FS) and a low fat diet (LF), since our pilot studies and the research of others suggest that these factors significantly alter prostate cancer progression. Our multidisciplinary team of nutritionists, urologists, pathologists and biostatistians propose a controlled clinical trial to test the effects of FS and LF on prostatic neoplasia and also explore potential hormonal mechanisms. Newly diagnosed, prostate cancer cases (N=160) who have greater than 3-week lag- time prior to prostatectomy will be block randomized into one of the following groups: 1) control; 2) FS (30 g/day); LF (less than or equal to 20 percent total energy); or 4) FS+LF. All subjects will be monitored and receive dietary instruction and supplies. Proliferation rate (MIB1) will serve as the primary endpoint to determine diet efficacy. Other endpoints include: apoptotic index (TUNEL), extent of high grade prostatic intraepithelial neoplasia and total serum prostate specific antigen. Given our pilot data which suggest that FS and LF diets may operate via a hormonal mechanism, potential hormonal mediators also will be assessed [i.e., total serum testosterone, free androgen index, insulin-like growth factor-1 (IGF-1) and IGF binding protein-3]. Nutritional biomarkers (i.e., lignan levels in prostatic fluid and urine, and erythrocyte and prostate fatty acid

Studies

51

profiles) also will be measured. Associations between nutritional biomarkers, hormonal mediators and study endpoints will be determined. The proposed study is structured to make an important contribution to what is known about diet and prostatic neoplasia. This research has the potential to expand the scope of complementary treatment offered for prostate cancer, and may provide a solid foundation for efforts aimed at prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REFLEXIVE TESTOSTERONE RELEASE IN MALES Principal Investigator & Institution: Nyby, John G.; Biological Sciences; Lehigh University Bethlehem, Pa 18015 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Many mammals, including humans, exhibit reflexive testosterone release during sexual encounters. However, the function of this release is unclear. This proposal is based upon the hypothesis that reflexive testosterone release has immediate effects upon the male's physiology and behavior to better prepare him to cope with the reproductive situation in which he finds himself. Scattered supportive evidence in the scientific literature indicates that testosterone treatment in rodents has quick effects in promoting male sexual reflexes and is experienced by male rodents as being rewarding, anxiolytic, and analgesic, all of which could potentially facilitate the expression of reproductive behavior. The proposed studies will test that hypothesis more explicitly by examining whether several different endpoints (reward and anxiety) in normal male mice are affected by the quick actions of testosterone when it is administered in such a way as to mimic naturally occurring testosterone release. Several questions will be addressed including 1) How does one best mimic the pulsatile testosterone release of gonadally intact males? 2) Is the reflexive release of testosterone experienced as rewarding in mice? 3) What level of sexual arousal is necessary before a male muse shows reflexive testosterone release? 4) Does the reflexive release of testosterone exert different effects upon physiology and behavior than spontaneous testosterone release in mice? The proposed research is basic research designed to better understand the role that reflexive testosterone release plays in normal male-typical behaviors. However, since reflexive testosterone release is evolutionarily conserved, we believe our results also will have relevance for understanding the same processes in other mammalian species including humans. Moreover, we believe that our results may also be directly relevant for understanding the seemingly addictive (i.e., rewarding) properties of anabolic steroid use in humans as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: REGULATION OF LEYDIG CELL MITOSIS AND DIFFERENTIATION Principal Investigator & Institution: Hardy, Matthew P.; Senior Scientist; Population Council 1 Dag Hammarskjold Plaza New York, Ny 10017 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 31-MAR-2004 Summary: The capacity for testosterone production in the adult male results from increases in Leydig cell numbers during puberty. Leydig cells increase in number through a gradual sequence of events in which Leydig cell precursors initially proliferate, than lower their rate of mitosis as they begin to express proteins that are characteristic of adult Leydig cells, most notably, steroidogenic enzymes. Studies of purified Leydig cells conducted by the PI and others, have defined discrete stages within the continuum of progressive Leydig cell differentiation: spindle shaped, highly proliferative progenitor Leydig cells; immature Leydig cells, which, though less

52

Testosterone

proliferative, remain in the cell cycle, contain steroidogenic organelles, synthesize steroids, but secrete 5alpha-reduced androgens rather than testosterone; adult Leydig cells, which do not divide and which secrete primarily testosterone. Luteinizing hormone (LH) controls Leydig cell function through LH receptors that are present in abundant numbers that the adult stage. However, Leydig cell progenitors have negligible numbers of LH receptors and are comparatively unresponsive to this hormone. These considerations led us to hypothesize that the beginning of Leydig cell development is regulated by other factors such as steroidogenic factor-1 (SF-1). LH is reported to increase Leydig cell numbers and is known to increase levels of testosterone production. This application focuses on two processes in which LH is unlikely to be the controlling stimulus: the decrease in mitotic rate during the transition from progenitor to immature Leydig cell; and stimulation of the androgen-metabolizing enzymes 5alpha- reductase and 3alpha-hydroxysteroid dehydrogenase, which lower testosterone secretion by progenitor and immature Leydig cells. Mullerian inhibiting substance (MIS) will be investigated because targeted deletion of the MIS gene causes Leydig cell hyperplasia, indicating that this factor is normally a growth inhibitor. In experiments planned for Specific Aim 1, we will determine if the reduction in progenitor Leydig cell mitosis, that is observed between days 14 and 21 postpartum in the rat, caused by MIS; establish whether testosterone-induced increases in mitosis of immature Leydig cells are required for terminal differentiation; investigate the involvement of estrogen in growth inhibition of the Leydig cells, because MIS is observed to regulate aromatase, the enzyme that catalyzes estradiol synthesis. The experiments planned for Specific Aim II will individually evaluate the regulation of testosterone biosynthetic and androgenmetabolizing enzyme activities by LH, testosterone, SF-1, and MIS; determine the extent of control of these enzymes by co-factor availability; and identify instances where steroidogenic enzyme activities are catalyzed by novel Leydig cell isoforms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF PDE 5 IN HUMAN PENILE SMOOTH MUSCLE CELLS Principal Investigator & Institution: Kim, Noel N.; Urology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-JUL-2003 Summary: The nitric oxide/cGMP signalling pathway is a major regulator of penile vascular smooth muscle tone and plays a critical role in erection. Phosphodiesterases, enzymes which hydrolyze cyclic nucleotides, are an integral part of this signalling pathway. Phosphodiesterase type 5 (PDE 5) is one of the main phosphodiesterases expressed in penile corpus cavernosum smooth muscle. Sildenafil, a reversible PDE 5 selective inhibitor, has been successfully utilized in the clinical treatment of erectile dysfunction. The efficacy of this inhibitor in ameliorating erectile function in men with impotence, resulting from a broad range of etiologies, emphasizes the crucial aspect which PDE5 plays in regulating penile smooth muscle tone. Yet the regulation of PDE 5 expression or activity is not well understood and the consequences of prolonged inhibition of this enzyme are unknown. Fundamental knowledge of the cellular and molecular mechanisms which regulate PDE 5 expression and/or activity is important to the understanding of erectile function. The novel perspective that intracellular cGMP levels are actively regulated by PDE 5 broadens our understanding of the cGMP signalling pathway and the integrated mechanisms which control penile trabecular smooth muscle tone. Thus, in this study we will investigate potential regulatory mechanisms which may alter the expression and/or activity of PDE 5 in human penile

Studies

53

corpus cavernosum smooth muscle. We will utilize primary cultures of human penile trabecular smooth muscle cells to study and characterize mechanisms of PDE 5 regulation without disrupting the intracellular regulatory pathways which are under investigation. Using cyclic nucleotide radioimmunoassays, Northern and Western blot analyses, and enzyme activity assays, we will investigate: 1) the effects of nitric oxide and cGMP on PDE 5 expression and/or activity; 2) the effects of cAMP and agonists which stimulate adenylate cyclase on PDE 5 expression and/or activity; 3) the effects of cAMP and agonists which stimulate adenylate cyclase on PDE 5 expression and/or activity; 4) cross-talk regulation between cyclic nucleotides and their respective protein kinases, and estrogen and testosterone signalling pathways. This investigation of multiple signalling systems and their influence on PDE 5 will increase our current understanding of the extensive nature by which distinct signalling pathways can interact and provide integrated regulation of smooth muscle tone. This work will provide new and useful information on regulation of PDE5 which will improve treatment strategies for management o erectile dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REWARD MOTIVATION

AND

REINFORCEMENT

IN

IMPLICIT

POWER

Principal Investigator & Institution: Schultheiss, Oliver C.; Psychology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (investigator's abstract): Although the implicit motive approach to human motivation has spawned a staggering amount of basic and applied research over the past 50 years, the processes at the core of implicit motives have received comparatively little attention in research. Specifically, there is a lack of empirical data elucidating why individuals high in a given motive seek to attain a motive-specific incentive in the first place and what consequences incentive consummation has for their behavior. For the case of the implicit power motive, the Principal Investigator has developed a model which posits that having impact - the incentive associated with the power motive - is rewarding for individuals high in implicit power motivation and reinforces behavior that was instrumental for having impact Importantly, because the power motive operates outside of a person's conscious awareness, individuals may be unaware of motive-based processes of reward and reinforcement These processes will therefore be assessed with objective behavioral and psychophysiological measures in the proposed research. Specifically, the gonadal steroid hormone testosterone is hypothesized to be an indicator of power motivation reward and to increase in high-power individuals in response to having impact. Enhanced implicit learning of behavior that was instrumental in having impact is hypothesized to reflect reinforcement in high-power individuals. Furthermore, the model states that power motivation reward, as indicated by surging testosterone, mediates power motivation reinforcement, as indicated by enhanced implicit learning. Three experimental studies on the role of personalized power motivation, a subtype of the implicit power motive, in winning or losing a dominance contest mark a first step towards validating this model. Study 1 will provide an initial test of the model in men, while Study 2 explores to which extent it also holds for women, in which estradiol may play a more important role than testosterone in power motivation reward. Study 3 will test whether the hypothesized rewarding effect of testosterone can be potentiated by a caffeine-induced increase of incentive motivation. In addition, the role of facial aflective expressions as indicators of power

54

Testosterone

motivation reward and the time course of the hypothesized power motivation reward and reinforcement effects will be explored in these studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE AGGRESSION

OF

ALPHA

&

BETA

ESTROGEN

RECEPTORS

IN

Principal Investigator & Institution: Ogawa, Sonoko; Lab/Neurobiology/Behavior; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract) It has been well established that testosterone facilitates aggression during social conflict, typically seen between male mice. Testosterone exerts its neural action not only by activating androgen receptors (AR), as its original form or as 5alpha-reduced metabolite, dihydrotesterone, but also by acting through estrogen receptors (ER), after being aromatized to estradiol. It has been previously described that activation of ER at the time of testing as well as during perinatal development plays a critical role in the induction of aggressive behavior in male mice and determines the sex differences in the levels of testosterone-inducible aggression. Two forms of ERs, a classical ER-alpha and a recently discovered ER-beta, are localized in the brain areas known to be involved in testosterone-inducible aggression. The main objective of the proposed studies is to determine the specific roles played by ER-alpha and ER-beta in the regulation of aggressive behavior. In the first part, we will determine the role of ER-beta activation, at the time of testing in adulthood, in the regulation of aggressive behavior of MALE mice by: 1) comparing the levels of estrogen-inducible aggression of ER-beta gene knockout (BERKO) mice (ERalpha specific activation) with those of their wild type littermates (BWT; ER-alpha and ER-beta activation); and 2) examining the effects of an ER-beta specific agonist on aggressive behavior induced by an ER-alpha specific agonist or an AR-specific agonist in WT male mice. In the second part of the proposal, we will determine the roles of ERalpha and ER-beta in testosterone-inducible aggression (toward male intruder mice) in FEMALE mice. The effects of testosterone treatment will be tested in three types of knockout mice: ER-alpha knockout (aERKO), BERKO, and double knockout of ER-alpha and ER-beta genes (dERKO). In the third part of the proposal, the possibility will be tested that aERKO FEMALE mice are "endogenously" sensitized for testosteroneinducible aggression by elevated levels of testosterone as a result of ER-alpha gene disruption. In the last part, we will test the hypothesis that neonatal ER-alpha, but not ER-beta, activation determines the responsiveness to aggression-promoting action of testosterone and its metabolites in adulthood, by manipulating neonatal steroid levels in FEMALE mice. The findings of the proposed studies will provide new insights concerning the specific roles and mechanisms played by the two types of ERs in the sexspecific regulation of aggressive behavior by gonadal steroids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF BENZODIAZEPINE RECEPTOR IN LEYDIG CELL FUNCTION Principal Investigator & Institution: Papadopoulos, Vassilios; Professor; Cell Biology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2006 Summary: (Adapted from the applicant's abstract) Trophic hormones acutely stimulate steroid production by acting on the rate-determining step of steroidogenesis, the

Studies

55

transport of the substrate, cholesterol, from intracellular stores to the inner mitochondrial membrane. There, cholesterol will be metabolized to pregnenolone. We demonstrated that the mitochondrial peripheral-type benzodiazepine receptor (PBR) mediates the transport of cholesterol from the outer to the inner mitochondrial membrane and the subsequent steroid biosynthesis. It is our hypothesis that PBR functions as a cholesterol binding protein and channel, thus allowing this steroid precursor to get into the outer membrane and cross from the outer to the inner mitochondrial membrane through the intermembrane contact sites. Therefore, the structure/state and levels of this lipid channel protein will determine the amount of cholesterol available for testosterone synthesis and consequently testicular function and fertility. In the first aim, we will examine the structure/function relationship of PBR. We were able to reconstitute a functional recombinant PBR that binds cholesterol with nM affinity and identified in vitro conditions that mimic the hormone-induced changes in PBR. Molecular (deletion mutations and site-directed mutagenesis), functional (cholesterol & drug ligand binding, cholesterol transport), structural (electron microscopy & two dimensional crystallization), and computational (molecular modeling and simulations) will be undertaken in order to define the structure of the receptor and its function as a channel for cholesterol (lipophorin). The function of PBR will be also examined in the second aim in cell and animal models where PBR levels are decreased leading to decreased testosterone production. Peroxisome proliferators (PPs), which are extensively used in humans, exert anti-androgenic activity and trigger testicular atrophy in rodents. PP hypolipidemic drugs and phthalate ester plasticizers inhibit Leydig cell steroidogenesis and PBR expression in vitro and in vivo. Based on preliminary studies we propose that the effect of PPs on PBR expression might be due to PP-activated receptor (PPAR)-mediated indirect transrepression of AP-1/CRE activity and/or to the activation of a novel PP-activated transcription factor (PPAF) and/or to the inhibition of binding of SRY/SOX-like or Nkx-like proteins to SRY- and Nkx-binding sites residing within the PBR promotor. To ascertain the in vitro effects of PPs on PBR gene transcription, the effect of PPs will be examined in in vivo experiments where the PBR upstream region(s), defined in the in vitro studies, will be used to drive the expression of the eGFP reporter gene in transgenic mice. Based on the in vivo data, the transcriptional mechanisms described above will be investigated in detail. It is our goal to elucidate the mode of action and define the health hazard risk of PPs on testicular function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROSIGLITAZONE IN POLYCYSTIC OVARY SYNDROME Principal Investigator & Institution: Cataldo, Nicholas A.; Assistant Professor of Obstetrics and Gy; Gynecology and Obstetrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (Adapted from applicant's description): Polycystic ovary syndrome (PCOS) is a disorder affecting about 5% of reproductive-age women characterized by anovulation and excess production of androgens by the ovary. Anovulation causes menstrual irregularity and infertility, while excess androgens cause unwanted hair growth and may promote acne. Traditional treatments for PCOS have consisted of medication to stimulate ovulation if fertility is desired, or medication to suppress or block androgents or restore regular menstrual cycles if fertility is not an immediate goal, but these treatments are often mutually exclusive PCOS is frequently associated with a common metabolic disorder, insulin resistance, and like insulin resistance alone carries an increased risk of non-reproductive health problems such as the development of diabetes

56

Testosterone

or atherosclerosis. Insulin resistance leads to excessive insulin secretion, and this may stimulate the ovary to hypersecrete androgens. In the last few years, published reports have described the treatment of PCOS with insulin sensitizers, medications developed to treat diabetes which can improve insulin resistance. These drugs can improve the hormonal abnormalities in PCOS and in some cases can restore regular menses and/or ovulation. Of the two marketed drugs tested to date, metformin has not been consistently effective, while troglitazone is effective but has been found to have an unacceptable risk of liver toxicity. This project will study rosiglitazone, a newly approved drug closely related to troglitazone in structure and action but without apparent toxicity, in an open-label, Phase II format. Subjects with PCOS wiII have insulin resistance identified by dynamic testing using the octreotide insulin suppression test, and after further evaluation of provoked insulin secretion will receive rosiglitazone daily in one of three doses for 12 weeks. Insulin resistance and insulin secretion, glucose tolerance, serum total and free testosterone, LH, and circulating lipids will be measured on rosiglitazone and compared to subjects' pretreatment values. The occurrence of ovulation will be evaluated by weekly serum progesterone levels. The dose of rosiglitazone and the time needed for its effect to develop will be determined. Associations between effects on metabolic parameters and effects on reproductive ones will be sought. The hypothesis of this study is that rosiglitazone can improve insulin sensitivity and lower circulating insulin, and thereby restore ovulation as well as correct elevated LH and testosterone. Rosiglitazone is potentially an appropriate and beneficial treatment for all women with PCOS and insulin resistance regardless of goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEX DIFFERENCES IN HYPOTHALAMO-PITUITARY-ADRENAL AXIS Principal Investigator & Institution: Handa, Robert J.; Professor; Anatomy and Neurobiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 15-JAN-2001; Project End 31-DEC-2003 Summary: (applicant's abstract): The focus of this proposal is to determine the mechanisms by which estrogen and testosterone act to influence peptide containing neurons in the paraventricular nucleus of the hypothalamus (PVN) that are involved in regulating endocrine responses to stress. Females exhibit a more robust adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stress when compared to males. This sex difference arises as a result of circulating adult hormone levels. Estrogen augments and testosterone suppresses stress related ACTH and CORT secretion. A novel form of estrogen receptor, termed beta (ER-beta), has been found in magnocellular and parvocellular neurons of the PVN, whereas the classically described alpha form is not present. ER-beta-containing neurons are uniquely distributed and may allow transduction of the estrogen signal to neuropeptide genes. In contrast androgen receptors (AR) are not found in neuroendocrine neurons of the PVN, but are found in neurons in the medial preoptic area (MPOA) and bed nucleus of the stria terminalis (BnST) that project to the PVN. This proposal describes studies to test the hypothesis that estrogen acts directly upon corticotropin releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXY) neurons in the PVN, whereas androgen acts indirectly by modulating GABAergic neurons in the MPOA and BnST that project to the PVN. 5 specific aims are proposed: 1) to determine if the local application of estrogen or testosterone to the PVN alters stress responsive hormone secretion, neuropeptide mRNA, protein content and heteronuclear RNA levels in the PVN. 2) To determine if androgen receptor or estrogen receptor act upon nucleotide sequences in the CRH, AVP

Studies

57

or OXY gene promoters. 3) To determine if AR positive, GABA positive neurons in the BnST project to the PVN. 4) To determine if estrogen or androgen modulate glucocorticoid receptor mediated negative feedback regulation of neuropeptide genes in the PVN. 5) To determine if ER-beta or AR interact with glucocorticoid receptor to regulate transcription of reporter genes downstream of the CRH, AVP or OXY gene promoters. Since a dysregulation of stress-responsive hormone secretion is a characteristic of affective disorders, and these are more prevalent in females than males, the long-term goals of this project are to define the role played by estrogen and androgen in the pathology of affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEX HORMONES SLEEP AND CIRCADIAN RHYTHMICITY IN AGING Principal Investigator & Institution: Murphy, Patricia J.; Associate Research Scientist; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-MAR-2003 Summary: Changes in the processes controlling sleep that accompany aging result in widespread complaints of sleep disturbance in otherwise healthy older individuals. It is likely that age-related changes in many physiological systems interact to produce these sleep problems. One such system is the hypothalamic-pituitary-gonadal (HPG) axis. Gonadal steroids exhibit significant declines with age, resulting in altered negative feedback to the hypothalamus, and unregulated production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent evidence demonstrates that these alterations continue and worsen with increasing age. That changing levels of gonadal hormones affect sleep quality in aging is supported by both anecdotal and empirical evidence. For example, up to two-thirds of perimenopausal women complain of sleep problems. Further, higher LH levels are associated with awakenings from sleep, and hormone replacement therapy improves objectively-measured sleep. Although investigations of sex hormones and sleep in men are rare, lower levels of testosterone in aging men have been associated with poorer sleep quality. Indeed, the few studies that have assessed sleep complaints in the context of age-associated changes in HPG functioning strongly suggest that further investigation is needed. In addition, while changes in the circadian timing system are widely believed to contribute to sleep problems in older individuals, little is known about whether circadian patterns of sex hormone release are modified as a function of aging. The proposed research plan combines a chronobiological approach to the study of changes in the HPG axis in aging with an investigation of whether sex hormone levels are associated with age-related sleep problems. One study will assess whether there are circadian rhythms in sex hormones independent of sleep, and whether patterns of gonadal hormone release are altered with aging. The second study will examine whether the balance of sex steroids and gonadotropins differs between older individuals without sleep complaints and those with sleep maintenance insomnia. The combination of findings from these studies will clarify our understanding of how sex hormones, sleep, and circadian rhythmicity interact in aging, providing an avenue for investigating hormone replacement therapies as treatments for sleep problems in older individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

58

Testosterone

•

Project Title: SEX HORMONES, RELATED POLYMORPHISMS & COGNITIVE DECLINE Principal Investigator & Institution: Yaffe, Kristine; Assistant Professor; Langley Porter Psychiatric Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant) The goal of this project is to determine the contributions of sex hormone levels and sex hormone-related gene variants (polymorphisms) to cognitive decline in older men and women and to compare this contribution among black and white elders. Over 33 percent of women and 20 percent of men aged 65 and older will develop dementia during their lifetime and many more will develop a milder form of cognitive impairment. Sex hormones, primarily estradiol and testosterone, may play an important role in maintenance of cognitive health. People who have low concentrations of these hormones may have more rapid cognitive decline than those with high levels. We propose to test this hypothesis by measuring serum levels of estradiol and testosterone and 4-year changes in levels in an ongoing prospective study of 3075 elderly black and white women and men. We will also determine whether physiologically-defined candidate genetic polymorphisms involved in sex hormone metabolism and hormone receptor function are associated with cognitive decline and may play an important role in maintaining cognitive function. As little is known about sex hormones and cognition in older black men and women, we will also determine if associations are similar for black and white elders. Our aims will be addressed as part of the 7- year NIH-funded Health, Aging and Body Composition (Health ABC) Study, currently finishing Year 5. The careful measurement of cognitive e function on multiple domains over 7 years, as well as having stored serum and extracted DNA, will allow for a very efficient approach to answering these questions. Further knowledge of the association between sex hormones, hormone-related polymorphisms and cognitive decline may facilitate preventative strategies to maintain independence and to promote optimum brain aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: SEX IN VIRAL MYOCARDITIS Principal Investigator & Institution: Huber, Sally A.; Professor; Pathology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): Myocarditis is an inflammatory disease of the myocardium. Approximately 65% of cases follow recent enterovirus infections and occur in males. As in humans, CVB3 infections cause severe myocarditis in male, but not virgin female mice. Androgens (progesterone and testosterone) increase virus receptor expression on cardiac myocytes while 17- beta-estradiol treatment does not. Since lymphocytes also express CVB3 receptors, we hypothesize that hormones might modulate lymphocyte expression of these molecules as well. Furthermore, enterovirus receptors often belong to immunoglobulin and integrin superfamilies, which have important signal transduction functions. Direct virus binding to normal lymphocytes causes rapid calcium flux and cytokine release within four hours of virus exposure. Cytokine release differs between male and female lymphocytes with male cells producing interferon (IFN)gamma and female cells producing interleukin (IL)- 10. We hypothesize that viruses, which have repetitive symmetry of the virus capsid, cross-link important cell surface molecules on lymphocytes and cause rapid non-antigen-specific

Studies

59

lymphocyte activation. This initial activation with associated cytokine release determines subsequent innate and adaptive immune responses to the virus, such as CD4+ T helper (Th) cell response and development/survival of autoimmune CD8+ T cells in vivo. The Specific Aims of this application are to: 1) Determine virus receptor expression, binding avidity, activation potential and cytokine production on male and female lymphoid cells exposed to non-infectious virus; 2) Determine the effects of direct virus interaction and hormone signaling on CD8+alpha,beta T cell receptor (TCR)+ and gamma,delta TCR+ effector cell function and survival in vivo; and 3) Determine the effects of direct virus interaction and hormone signaling on virus-specific CD4+alpha,beta TCR+ response and survival in vivo. These studies may provide new insights as to how viruses affect developing host defense responses and how hormones can modulate this initial response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION

SEXUAL

DIFFERENTIATION

OF

MOUSE

VOMERONASAL

Principal Investigator & Institution: Cherry, James A.; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-DEC-1998; Project End 31-MAR-2005 Summary: (provided by applicant): The vomeronasal organ (VNO) projection pathway mediates many of the effects of pheromones on essential psychosexual and neuroendocrine functions in a variety of vertebrate species. We have shown that different populations of neurons in the VNO of male and female mice respond to pheromones derived from male and female conspecifics and that estradiol and testosterone amplify these effects. Experiments are proposed to extend these findings by determining whether sex differences exist in the expression within the basal zone of the VNO of any three different V2R receptors previously cloned in mice, and whether any such differences in mRNA levels for these receptors are modulated by estradiol or testosterone. We will see whether the ability of male pheromones to augment Fos-IR in mitral cells that project to medial amygdaloid nuclei from the rostral as opposed to the caudal AOB differs in gonadectomized, estrogen-treated male and female mice and will use cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH) for the immediate-early-gene (IEG), c-fos, to determine whether mitral cells in the rostral versus caudal zones of the AOB are differentially activated by pheromones from male versus estrous female mice. Finally, we will determine whether the inhibition of male pheromone-induced IEG activation previously seen in the VNO of females two days after mating also occurs in male mice and in response to pheromones from both sexes, and we will assess the possible role of noradrenergic afferents from the superior cervical ganglia on the mating-induced 'silencing' of subsequent odor-induced IEG activation in the VNO. The results obtained in these studies should improve our understanding of the neurobiological mechanisms that underlie the effects of gender, steroid hormones, and previous coital experience on the processing of olfactory signals by the accessory olfactory system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEM CELLS AND PERINATAL FACTORS FOR BREAST CANCER RISK Principal Investigator & Institution: Hsieh, Chung-Cheng; Professor of Medicine; Cancer Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655

60

Testosterone

Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-JAN-2006 Summary: (provided by applicant): This study proposes to examine whether hormone levels in human umbilical cord blood are associated with measurements of stem cell potential and expression of Bcl-2 family proteins indicating levels of apoptotic activity. Measurements of stem cells and Bcl-2 apoptosis will be further examined to see if they correlate with birth weight as an indicator of fetal growth. The study is based on the hypothesis that cancer risk can be influenced in part by the hormonal environment in utero and that cancer risk is proportional to the number of primitive proliferating stem cells. Umbilical cord blood from 300 donors will be obtained from singleton birth, fullterm, and low-risk deliveries at hospitals affiliated with the American Red Cross Cord Blood Program. Hormones and other growth factors including estradiol, estriol, progesterone, prolactin, sex-hormone binding globulin (SHIBG), testosterone, insulinlike growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3) will be assayed in cord blood samples. We will measure the total number of nucleated cells, number of cells per volume expressing CD34 protein on the cell surface as well as CD34+/CD38, CD34+/c-kit, and CD45/GlyA sub-population cells, and the number of colony-formingunit granulocytes and macrophages (CFU-GM) as laboratory parameters for primitive proliferating stem cells. Among Bcl-2 family proteins we will measure the expression of Bcl-2, Bcl-xL, Bax, and Bad to construct an overall apoptotic index. We will apply regression analysis treating as outcome variables each measurement of stem cell potential and Bcl-2 apoptotic index and as predictor variables hormone levels, controlling for maternal and neonatal characteristics. Stem cell measurements and index of Bcl-2 apoptotic expressions will be further examined as predictors of birth weight. The study seeks to obtain information on parameters of perinatal cell proliferation relevant to intervening steps between intrauterine hormone exposure and subsequent cancer risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEROID HORMONES AND NEURONAL REGENERATION Principal Investigator & Institution: Jones, Kathryn J.; Professor; Cell Bio & Neurobio & Anatomy; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-JAN-1990; Project End 31-JUL-2002 Summary: The investigator has identified a role for testosterone propionate (TP) in enhancing neuronal regeneration of the crushed facial nerve in adult hamsters. It is thought that testosterone mediates its actions through androgen receptors (AR) that are more prevalent in males than in females and are present at the surface of this particular neuronal subtype. Previously, a working model of the mechanism by which steroids augment peripheral nerve regeneration has been developed. The main objective of this project is to test specific aspects of this model, with particular focus on the initial injury phases of the regenerative response and on the role of the androgen receptor in these early phenomena. The aims are to test the following 4 hypotheses. First, it was shown that TP administration coincident with facial nerve injury alters early stress responses of injured FMN. Two series of experiments, utilizing northern blot and immunoblot procedures in conjunction with heat shock protein 70 cDNA probes and antibodies will be used to determine the effect of TP on the stress response of injured FMN. Second, the effects of TP on facial nerve regeneration occur during the initial stages of the FMN injury response although all previous studies have used TP administration for lengthy time periods. To learn if TP can work early on, TP exposure will be limited to time periods of 6-2 hours after facial nerve injury and 2 series of analyses will be done. Radioisotopic labeling procedures will be used to determine the effects of limited Tp

Studies

61

exposure on the rate of facial nerve regeneration, and in situ hybridization studies with cytoskeletal probes will be done to determine the effects of limited TP exposure on cytoskeletal response patterns throughout the recovery period. Third, the gender differences in the augmentation of facial nerve regeneration by TP are AR mediated. In 3 series of experiments, females will receive TP prior to facial nerve injury, in order to upregulate levels of AR mRNA to those of males, and the effects of TP on facial nerve regeneration, and rRNA/cytoskeletal gene expression will be determined. Fourth, estradiol (E) acts via AR to augment racial nerve regeneration. It has been shown that E given from the time of facial nerve injury, results in an androgen- like acceleration of regeneration rates. Two series of experiments will be done. The effects of high doses of E in the presence of the anti-androgen, flutamide, and high versus low doses of E on the rate of regeneration will be determined. AR binding assays will also be done to determine if E binds to AR in the facial nucleus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEROIDOGENIC ENZYME CHANGE AFTER TNFA & LEPTIN EXPOSURE Principal Investigator & Institution: Watson, Angela M.; Jackson State University 1400 John R. Lynch St Jackson, Ms 39217 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-DEC-2005 Summary: Many changes occur in experimental animals (ob/ob mice) as a result of obesity. The ob/ob mice have been shown to be diabetic and have an increased level of insulin as well as corticosterone (Uysal et al., 1997). Others have also shown that there is an increased level of the cytokine, TNF-alpha, in the serum of these mice (Hotamisligil, 1993) which has been shown to cause a decrease in the level of testosterone in vitro (Xiong and Hales, 1993a). Regulation and expression of certain steroidogenic enzymes such as CYPO17c and CYPscc have been shown to be decreased following in vitro exposure of mouse Leydig cells to TNF-alpha. Changes in the steroidogenic enzymes may lead to decreased levels of testosterone which could ultimately affect the sterility of these animals. In this study, several protocols have been proposed that will be utilized to elucidate the mechanism by which TNF-alpha causes reduction of certain steroidogenic enzymes. The hypothesis of this study is that the increase in TNF-alpha, secondary to obesity, may cause a reduction in the levels or activity of some or all of the steroidogenic enzymes producing a decrease in testosterone production. A prolonged decrease in testosterone levels or production may affect spermatogenesis and thus contribute to male infertility or subfertility. Specifically, I propose the following: 1) To determine the changes in steroidogenic enzymes following the treatment of lean and ob/ob mice with TNF- alpha; 2) To determine the changes in steroidogenic enzymes following the treatment of lean and ob/ob mice with pentoxyfilline and antibodies directed to TNF-alpha; and 3) To determine the changes in steroidogenic enzymes in TNF-alpha receptor (both receptors) knockout ob/ob mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: STEROIDS STIMULATE AXON REGENERATION IN THE ADULT BRAIN Principal Investigator & Institution: Kuhn, Thomas B.; None; University of Alaska Fairbanks 109 Admin Services Center Fairbanks, Ak 997757880 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002

62

Testosterone

Summary: The proper fusion of the adult nervous system depends on a precise pattern of neuronal connections established during development. In higher vertebrates, neuronal plasticity in the central nervous system is limited to modifications of the morphology and efficacy of synapses. In contrast, songbirds exhibit a tremendous degree of neuronal plasticity in the adult CNS. Several brain nuclei, associated with learning and production of song, undergo dramatic, seasonal changes and correlated with fluctuating plasma testosterone levels. High plasma testosterone levels induce increases in neuronal cell number in the hyperstriatum ventrale pars caudale (HVc) by as much as 50% with a daily rate of addition of new neurons reaching 0.5%. The majority of new HVc-neurons project axons through densely myelinated brain regions to their target neurons in the robust nucleus of the archistriatum (RA). There is strong evidence that testosterone regulates post-mitotic events rather than cellular proliferation. This proposal will investigate the role of testosterone in stimulating axon outgrowth in the presence of myelin resulting in th formation of functional neuronal connections. This in vitro study will utilize HVc-neurons in dissociated cultures and seeded onto cryosections of adult songbirds brain. Furthermore, axon guidance mechanisms of HVc- neurons will be addressed in living, long-term brain slice preparations. HVc-neurons to be studied will be labeled with DiI and by adenoviralmediated expression of green fluorescent protein and/or beta- galactosidase. Expression of these reporter genes is driven by various promoters to achieve exclusive expression in HV/c-neurons or other neuronal population associated with learning and production of song. Key methods employed in the proposed research include live video microscopy under phase and DIC optics, fluorescence microscopy, immunocytochemical and histochemical staining. Understanding the principal of testosteronedependent axon outgrowth in the presence of myelin could improve our knowledge to address functional regeneration in the adult mammalian CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRATEGIES TO IMPROVE COPD MANAGEMENT Principal Investigator & Institution: Casaburi, Richard; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The Harbor-UCLA Research and Education Institute is highly qualified to be a vigorous and committed site in the COPD Clinical Research Network. The Principal Investigator leads 10 investigators and 3 consultants with broad experience in COPD clinical research. The research facilities are arrayed around a 4000 ft 2 Clinical Trials Center dedicated to COPD research, and include this institution's NIHsupported GCRC. This Center has extensive experience in recruiting COPD patients for both single and multi-center research protocols. Referral resources are solidly in place and have led to success in recruiting a gender-balanced and multi-ethnic population for COPD trials. A total of 20 clinical trials in COPD have been completed in the past two years or are underway. This site is able to perform a wide range of procedures that might be utilized in the network's trials, with special expertise in physiologic testing. We target two especially poor-prognosis COPD groups: chronically hypoxemic patients and patients with weight loss. Both trials focus on determining whether treatments we propose alter survival, though a range of other outcomes will be explored. Protocol 1 is based on the observation that expert opinion holds that lightweight ambulatory oxygen supply is of benefit to hypoxemic COPD patients even though most patients, in practice, are supplied with much heavier E-cylinders. A randomized 18-month trial involving 252 patients will determine whether, compared to patients receiving E-cylinders, patients

Studies

63

assigned to lightweight oxygen supply will have increased activities of daily living, use more hours of oxygen per day, have better retention of muscle mass and exercise tolerance, have fewer exacerbations and lower medical resource utilization and, ultimately, have superior survival. Protocol 2 recognizes recent work suggesting that prognosis of underweight COPD patients is improved by weight gain and that muscle dysfunction is a reversible cause of exercise intolerance. We build on our recent demonstrations that testosterone increases muscle mass and strength in COPD men and that megestrol acetate stimulates appetite and increases body weight in COPD. A double-blind, placebo-controlled study involving 225 underweight COPD men is proposed in which 3 groups receive 6 months of 1) placebo, 2) testosterone enanthate 150mg/wk, or 3) testosterone plus megestrol acetate 800mg/day, each for 6 months followed by 12 months of observation. We will determine whether these interventions increase lean and total body mass, decrease systemic inflammation, increase activities of daily living, muscle strength, exercise endurance and quality of life, and thereby improve survival. These studies should have immediate impact on treatment strategies for large poor-prognosis subgroups of COPD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TESTOSTERONE DIFFERENTIATION

EFFECTS

ON

PLURIPOTENT

CELL

Principal Investigator & Institution: Gonzalez-Cadavid, Nestor F.; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, Ca 90059 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: Testosterone (T) administration increases skeletal muscle mass in men, causing hypertrophy of type I and II fibers, and increasing myonuclei and satellite cells, while reducing fat mass. We propose that these effects are due in part to the modulation of the conversion of pluripotent cells (PPC) residing in the skeletal muscle into myogenic and adipogenic lineages. Our hypothesis is that androgens stimulate through an androgen receptor (AR) mechanism: 1) the in vitro conversion of embryonic mesodermal PPC into the myogenic lineage, while inhibiting their adipogenic potential, and these effects can be replicated in cultures of non-embryonic PPC from mouse muscle; and 2) the conversion of non-embryonic PPC into satellite-like cells, which would donate their nuclei into pre-existing fibers, both in vitro and in vivo. Our Aim 1 is to determine in vitro whether: a) T and DHT modulate embryonic non-muscle PPC differentiation into myogenic or adipogenic lineages through an AR-dependent mechanism; and b) these effects can be replicated in primary cultures of PPC from mouse muscle. For a) we will characterize in the mouse C3H/10T1/2 cell line, the effects of increasing doses of T and DHT, without or with an AR antagonist, on: i) myogenesis, utilizing early, intermediate, and late markers; and ii) adipogenesis, utilizing early and late markers. Measurements will be performed by quantitative immunocytochemistry, western blot, and RT/PCR. For b) we will perform similar determinations on PPC cultures from young mouse muscle: the regenerating muscle fibroblasts (RMF) and/or the side-population (SP) cells. Our Aim 2 is to determine whether: a) androgen stimulation of myogenic conversion of the muscle PPC in vitro generates satellite-like cells that donate their nuclei to myotubes in an AR-dependent process; and b) whether this occurs in vivo in PPC explants into mouse skeletal muscle. For a) we will label the nuclei of muscle PPC, and incubate PPC with mouse C2C12 myoblasts or myotubes, to determine whether androgens stimulate MyoD expression and the fusion of the donor nuclei into myotubes, in an AR-dependent pathway. For b), the labeled PPC will be implanted in vivo into regenerating muscle, in intact and castrated nude mice treated or

64

Testosterone

not with T, applying the same end-points as in vitro. These studies would provide novel insights on the mechanisms of androgen action and have implications for potential therapeutic uses of androgens for aging-related sarcopenia and other conditions associated with loss of muscle mass and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “testosterone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for testosterone in the PubMed Central database: •

Act locally and think globally: Intracerebral testosterone implants induce seasonallike growth of adult avian song control circuits. by Brenowitz EA, Lent K.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129460

•

Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone. by Lin TM, Chang C.; 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24618

•

Complex gangliosides are essential in spermatogenesis of mice: Possible roles in the transport of testosterone. by Takamiya K, Yamamoto A, Furukawa K, Zhao J, Fukumoto S, Yamashiro S, Okada M, Haraguchi M, Shin M, Kishikawa M, Shiku H, Aizawa S, Furukawa K.; 1998 Oct 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22799

•

Effects of ciprofloxacin on testosterone and cortisol concentrations in healthy males. by Waite NM, Edwards DJ, Arnott WS, Warbasse LH.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172780

•

Expression of somatostatin receptor type-2 (sst2A) in immature porcine Leydig cells and a possible role in the local control of testosterone secretion. by Fombonne J, Csaba Z, von Boxberg Y, Valayer A, Rey C, Benahmed M, Dournaud P, Krantic S.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151791

•

Feed-Forward Control of Prostate Growth: Dihydrotestosterone Induces Expression of Its Own Biosynthetic Enzyme, Steroid 5[alpha]-Reductase. by George FW, Russell DW, Wilson JD.; 1991 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52442

3 Adapted 4

from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

Studies

65

•

Fluconazole and testosterone: in vivo and in vitro studies. by Hanger DP, Jevons S, Shaw JT.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172246

•

Functional Specific Binding of Testosterone to Schistosoma haematobium 28Kilodalton Glutathione S-Transferase. by Remoue F, Mani JC, Pugniere M, Schacht AM, Capron A, Riveau G.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127730

•

Gene Encoding the Hydrolase for the Product of the meta-Cleavage Reaction in Testosterone Degradation by Comamonas testosteroni. by Horinouchi M, Hayashi T, Koshino H, Yamamoto T, Kudo T.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154777

•

Localization of 17[beta]-Hydroxysteroid Dehydrogenase and Characterization of Testosterone in the Brain of the Male Frog. by Mensah-Nyagan AG, Feuilloley M, DoRego JL, Marcual A, Lange C, Tonon MC, Pelletier G, Vaudry H.; 1996 Feb 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39954

•

Long-Lived Testosterone Esters in the Rat. by Borg W, Shackleton CH, Pahuja SL, Hochberg RB.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42556

•

Male-Specific Expression of Mouse Sex-Limited Protein Requires Growth Hormone, not Testosterone. by Georgatsou E, Bourgarel P, Meo T.; 1993 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46354

•

Mullerian Inhibiting Substance lowers testosterone in luteinizing hormonestimulated rodents. by Trbovich AM, Sluss PM, Laurich VM, O'Neill FH, MacLaughlin DT, Donahoe PK, Teixeira J.; 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30664

•

Mumps Virus Decreases Testosterone Production and Gamma Interferon-Induced Protein 10 Secretion by Human Leydig Cells. by Le Goffic R, Mouchel T, Ruffault A, Patard JJ, Jegou B, Samson M.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149733

•

Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males. by Pincus SM, Mulligan T, Iranmanesh A, Gheorghiu S, Godschalk M, Veldhuis JD.; 1996 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19501

•

Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: Progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. by Morley JE, Kaiser F, Raum WJ, Perry HM III, Flood JF, Jensen J, Silver AJ, Roberts E.; 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23857

66

Testosterone

•

Prolonged Inhibition of Luteinizing Hormone and Testosterone Levels in Male Rats with the Luteinizing Hormone-Releasing Hormone Antagonist SB-75. by Bokser L, Bajusz S, Groot K, Schally AV.; 1990 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54691

•

Protective Effect of Medroxyprogesterone Acetate Plus Testosterone Against Radiation-Induced Damage to the Reproductive Function of Male Rats and Their Offspring. by Jegou B, Velez de la Calle JF, Bauche F.; 1991 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52579

•

Salivary testosterone levels in preadolescent children. by Ostatnikova D, Pastor K, Putz Z, Dohnanyiova M, Mat'aseje A, Hampl R.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116575

•

Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: Implications in atherosclerosis. by Mukherjee TK, Dinh H, Chaudhuri G, Nathan L.; 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122647

•

Testosterone Facilitates Some Conspecific Song Discriminations in Castrated Zebra Finches (Taeniopygia guttata). by Cynx J, Nottebohm F.; 1992 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48453

•

Testosterone in Egg Yolks: An Ornithologist's Perspective. by Winkler DW.; 1993 Dec 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=47998

•

Testosterone in utero and at birth dictates how stressful experience will affect learning in adulthood. by Shors TJ, Miesegaes G.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129804

•

Testosterone Increases the Recruitment and/or Survival of New High Vocal Center Neurons in Adult Female Canaries. by Rasika S, Nottebohm F, Alvarez-Buylla A.; 1994 Aug 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44502

•

Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase. by Nathan L, Shi W, Dinh H, Mukherjee TK, Wang X, Lusis AJ, Chaudhuri G.; 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30697

•

Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3[beta] but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of [tau]: Implications for Alzheimer's disease. by Papasozomenos SC, Shanavas A.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122157

•

Testosterone reduces neuronal secretion of Alzheimer's [beta]-amyloid peptides. by Gouras GK, Xu H, Gross RS, Greenfield JP, Hai B, Wang R, Greengard P.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15568

Studies

67

•

Testosterone Signaling through Internalizable Surface Receptors in Androgen Receptor-free Macrophages. by Benten WP, Lieberherr M, Stamm O, Wrehlke C, Guo Z, Wunderlich F.; 1999 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25566

•

Testosterone-regulated expression of enzymes involved in steroid and aromatic hydrocarbon catabolism in Comamonas testosteroni. by Mobus E, Jahn M, Schmid R, Jahn D, Maser E.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179490

•

Widespread accumulation of [3H]testosterone in the spinal cord of a wild bird with an elaborate courtship display. by Schultz JD, Schlinger BA.; 1999 Aug 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17905

•

Yolk is a Source of Maternal Testosterone for Developing Birds. by Schwabl H.; 1993 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48000

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with testosterone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “testosterone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for testosterone (hyperlinks lead to article summaries): •

“Mitochondrial Eve”, “Y Chromosome Adam”, testosterone, and human evolution. Author(s): Howard JM. Source: Riv Biol. 2002 May-August; 95(2): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12449688&dopt=Abstract

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

68

Testosterone

•

A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men. Author(s): von Eckardstein S, Noe G, Brache V, Nieschlag E, Croxatto H, Alvarez F, Moo-Young A, Sivin I, Kumar N, Small M, Sundaram K; International Committee for Contraception Research, The Population Council. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5232-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602755&dopt=Abstract

•

A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. Author(s): Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK, Huang ZJ, Zhang GY. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 562-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574181&dopt=Abstract

•

A novel testosterone 6 beta-hydroxylase activity assay for the study of CYP3Amediated metabolism, inhibition, and induction in vitro. Author(s): Fayer JL, Petullo DM, Ring BJ, Wrighton SA, Ruterbories KJ. Source: Journal of Pharmacological and Toxicological Methods. 2001 SeptemberOctober; 46(2): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481849&dopt=Abstract

•

A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function. Author(s): McNicholas TA, Dean JD, Mulder H, Carnegie C, Jones NA. Source: Bju International. 2003 January; 91(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614254&dopt=Abstract

•

A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Author(s): Tan RS, Pu SJ. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2003 March; 6(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809076&dopt=Abstract

•

A quantitative trait locus on chromosome 22 for serum leptin levels adjusted for serum testosterone. Author(s): Martin LJ, Mahaney MC, Almasy L, Hixson JE, Cole SA, MacCluer JW, Jaquish CE, Blangero J, Comuzzie AG. Source: Obesity Research. 2002 July; 10(7): 602-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105281&dopt=Abstract

Studies

69

•

A research on the relationship between ejaculation and serum testosterone level in men. Author(s): Jiang M, Xin J, Zou Q, Shen JW. Source: J Zhejiang Univ Sci. 2003 March-April; 4(2): 236-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659241&dopt=Abstract

•

A round table to avoid going round in circles and missing the testosterone decline phenomenon in aging males. Author(s): Pugeat M. Source: Annales D'endocrinologie. 2003 April; 64(2): 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773943&dopt=Abstract

•

A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer. Author(s): Perez-Marreno R, Chu FM, Gleason D, Loizides E, Wachs B, Tyler RC. Source: Clinical Therapeutics. 2002 November; 24(11): 1902-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501882&dopt=Abstract

•

AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. Author(s): Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R; North American AA2500 T Gel Study Group. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2673-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788872&dopt=Abstract

•

Activation of the somatotropic axis by testosterone in adult men: evidence for a role of hypothalamic growth hormone-releasing hormone. Author(s): Bondanelli M, Ambrosio MR, Margutti A, Franceschetti P, Zatelli MC, degli Uberti EC. Source: Neuroendocrinology. 2003 June; 77(6): 380-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845224&dopt=Abstract

•

Acute haemodynamic effects of testosterone in men with chronic heart failure. Author(s): Pugh PJ, Jones TH, Channer KS. Source: European Heart Journal. 2003 May; 24(10): 909-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714022&dopt=Abstract

•

Acute influences of estrogen and testosterone on divergent and convergent thinking in postmenopausal women. Author(s): Krug R, Molle M, Dodt C, Fehm HL, Born J. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 August; 28(8): 1538-45. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784108&dopt=Abstract

70

Testosterone

•

Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being. Author(s): Floter A, Nathorst-Boos J, Carlstrom K, von Schoultz B. Source: Climacteric : the Journal of the International Menopause Society. 2002 December; 5(4): 357-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626215&dopt=Abstract

•

Age-related change in serum concentrations of testosterone in middle-aged Korean men. Author(s): Kang YG, Bae CY, Kim S, Kim MJ, Lee YJ, Seo J, Kim YC. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2003 March; 6(1): 8-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809075&dopt=Abstract

•

Aggression: the testosterone-serotonin link. Author(s): Birger M, Swartz M, Cohen D, Alesh Y, Grishpan C, Kotelr M. Source: Isr Med Assoc J. 2003 September; 5(9): 653-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509157&dopt=Abstract

•

An integrative review on current evidence of testosterone replacement therapy for the andropause. Author(s): Tan RS, Culberson JW. Source: Maturitas. 2003 May 30; 45(1): 15-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753940&dopt=Abstract

•

An investigation of the effectiveness of testosterone implants in combination with the prolactin inhibitor quinagolide in the suppression of spermatogenesis in men. Author(s): Hair WM, Wu FC, Lincoln GA. Source: Human Reproduction (Oxford, England). 2003 April; 18(4): 749-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660266&dopt=Abstract

•

Anemia, testosterone, and pituitary adenoma in men. Author(s): Ellegala DB, Alden TD, Couture DE, Vance ML, Maartens NF, Laws ER Jr. Source: Journal of Neurosurgery. 2003 May; 98(5): 974-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744356&dopt=Abstract

•

Anticipatory cortisol, testosterone and psychological responses to judo competition in young men. Author(s): Salvador A, Suay F, Gonzalez-Bono E, Serrano MA. Source: Psychoneuroendocrinology. 2003 April; 28(3): 364-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573302&dopt=Abstract

Studies

71

•

Apolipoprotein E epsilon4 and testosterone interact in the risk of Alzheimer's disease in men. Author(s): Hogervorst E, Lehmann DJ, Warden DR, McBroom J, Smith AD. Source: International Journal of Geriatric Psychiatry. 2002 October; 17(10): 938-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12325053&dopt=Abstract

•

Apolipoprotein E gene determines serum testosterone and dehydroepiandrosterone levels in postmenopausal women. Author(s): Zofkova I, Zajickova K, Hill M, Horinek A. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 October; 147(4): 503-6. Erratum In: Eur J Endocrinol. 2003 May; 148(5): 587. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370113&dopt=Abstract

•

Assays for testosterone in plasma: untested assays for an unproven syndrome. Author(s): Rosner W. Source: Annales D'endocrinologie. 2003 April; 64(2): 115. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773945&dopt=Abstract

•

Association between prostate cancer and serum testosterone levels. Author(s): Zhang PL, Rosen S, Veeramachaneni R, Kao J, DeWolf WC, Bubley G. Source: The Prostate. 2002 November 1; 53(3): 179-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386917&dopt=Abstract

•

Association of dehydroepiandrosterone sulfate and testosterone deficiency with bone turnover in men with inflammatory bowel disease. Author(s): Szathmari M, Vasarhelyi B, Treszl A, Tulassay T, Tulassay Z. Source: International Journal of Colorectal Disease. 2002 March; 17(2): 63-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014422&dopt=Abstract

•

Associations of serum testosterone with microvessel density, androgen receptor density and androgen receptor gene polymorphism in prostate cancer. Author(s): Schatzl G, Madersbacher S, Haitel A, Gsur A, Preyer M, Haidinger G, Gassner C, Ochsner M, Marberger M. Source: The Journal of Urology. 2003 April; 169(4): 1312-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629350&dopt=Abstract

•

Basal serum testosterone as an indicator of response to clomiphene treatment in human epididymis, seminal vesicles and prostate. Author(s): Gonzales GF. Source: Andrologia. 2002 October; 34(5): 308-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390089&dopt=Abstract

72

Testosterone

•

Basal testicular testosterone production in endurance-trained men is suppressed. Author(s): Hackney AC, Szczepanowska E, Viru AM. Source: European Journal of Applied Physiology. 2003 April; 89(2): 198-201. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665985&dopt=Abstract

•

Beneficial effects of testosterone replacement for the nonmotor symptoms of Parkinson disease. Author(s): Okun MS, Walter BL, McDonald WM, Tenover JL, Green J, Juncos JL, DeLong MR. Source: Archives of Neurology. 2002 November; 59(11): 1750-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433262&dopt=Abstract

•

Bioavailable testosterone as index of androgenicity (from 1973 to 2003). Author(s): Tremblay RR. Source: Annales D'endocrinologie. 2003 April; 64(2): 116. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773946&dopt=Abstract

•

Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism. Author(s): Tengstrand B, Carlstrom K, Hafstrom I. Source: Rheumatology (Oxford, England). 2002 March; 41(3): 285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934965&dopt=Abstract

•

Bio-available testosterone levels fall acutely following myocardial infarction in men: association with fibrinolytic factors. Author(s): Pugh PJ, Channer KS, Parry H, Downes T, Jone TH. Source: Endocrine Research. 2002 August; 28(3): 161-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489566&dopt=Abstract

•

Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Author(s): Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, Clezardin P. Source: Cancer Research. 2002 November 15; 62(22): 6538-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438248&dopt=Abstract

•

Bone mineral density in hypogonadal men remains low after long-term testosterone replacement. Author(s): Ishizaka K, Suzuki M, Kageyama Y, Kihara K, Yoshida K. Source: Asian Journal of Andrology. 2002 June; 4(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085102&dopt=Abstract

Studies

73

•

Bone mineral density outcomes following long-term treatment with subcutaneous testosterone pellet implants in male hypogonadism. Author(s): Zacharin MR, Pua J, Kanumakala S. Source: Clinical Endocrinology. 2003 June; 58(6): 691-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780744&dopt=Abstract

•

Can sublingual testosterone increase subjective and physiological measures of laboratory-induced sexual arousal? Author(s): Tuiten A, van Honk J, Verbaten R, Laan E, Everaerd W, Stam H. Source: Archives of General Psychiatry. 2002 May; 59(5): 465-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982451&dopt=Abstract

•

Candida albicans in urine can produce testosterone: impact on the testosterone/epitestosterone sports drug test. Author(s): Kicman AT, Fallon JK, Cowan DA, Walker C, Easmon S, Mackintosh D. Source: Clinical Chemistry. 2002 October; 48(10): 1799-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324504&dopt=Abstract

•

Cardiovascular effects of testosterone: implications of the “male menopause”? Author(s): Channer KS, Jones TH. Source: Heart (British Cardiac Society). 2003 February; 89(2): 121-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527649&dopt=Abstract

•

Characterization of endozepines in the human testicular tissue: effect of triakontatetraneuropeptide on testosterone secretion. Author(s): Duparc C, Lefebvre H, Tonon MC, Vaudry H, Kuhn JM. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5521-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602800&dopt=Abstract

•

Characterization of testosterone metabolism and 7-hydroxycoumarin conjugation by rat and human liver slices after storage in liquid nitrogen for 1 h up to 6 months. Author(s): Granhall C, Floby E, Nordmark A, Orzechowski A, Thorne A, Tybring G, Sohlenius-Sternbeck AK. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 2002 November; 32(11): 985-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487728&dopt=Abstract

74

Testosterone

•

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit? Author(s): Guay AT, Jacobson J, Perez JB, Hodge MB, Velasquez E. Source: International Journal of Impotence Research : Official Journal of the International Society for Impotence Research. 2003 June; 15(3): 156-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904801&dopt=Abstract

•

Combined treatment with testosterone (T) and ethinylestradiol (EE2) in constitutionally tall boys: is treatment with T plus EE2 more effective in reducing final height in tall boys than T alone? Author(s): Decker R, Partsch CJ, Sippell WG. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 1634-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932294&dopt=Abstract

•

Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire. Author(s): Lobo RA, Rosen RC, Yang HM, Block B, Van Der Hoop RG. Source: Fertility and Sterility. 2003 June; 79(6): 1341-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798881&dopt=Abstract

•

Comparison of stimulated growth hormone levels in primed versus unprimed provocative tests: effect of various testosterone doses on growth hormone levels. Author(s): Simic-Schleicher G. Source: Hormone Research. 2002; 58(4): 187. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324717&dopt=Abstract

•

Consensus Document on substitution therapy with testosterone in hypoandrogenic elderly men. Author(s): Valenti G, Bossoni S, Giustina A, Maugeri D, Motta M, Vigna GB, Fellin R, Corica F, Corsonello A, Paolisso G, Barbagallo M, Dominguez L, Denti L, Ceda G, Ferrari E, Pontiggia B, Strollo F; Italian Study Group on Geriatric Endocrinology. Source: Aging Clin Exp Res. 2002 December; 14(6): 439-64. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674485&dopt=Abstract

•

Crystal structure of an in vitro affinity- and specificity-matured anti-testosterone Fab in complex with testosterone. Improved affinity results from small structural changes within the variable domains. Author(s): Valjakka J, Hemminki A, Niemi S, Soderlund H, Takkinen K, Rouvinen J. Source: The Journal of Biological Chemistry. 2002 November 15; 277(46): 44021-7. Epub 2002 August 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196551&dopt=Abstract

Studies

75

•

CSF testosterone in 43 male suicide attempters. Author(s): Gustavsson G, Traskman-Bendz L, Higley JD, Westrin A. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 March; 13(2): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650954&dopt=Abstract

•

Defining 'relative' androgen deficiency in aging men: how should testosterone be measured and what are the relationships between androgen levels and physical, sexual and emotional health? Author(s): Haren MT, Morley JE, Chapman IM, O'Loughlin PD, Wittert GA. Source: Climacteric : the Journal of the International Menopause Society. 2002 March; 5(1): 15-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974555&dopt=Abstract

•

Determination of testosterone metabolites in human hepatocytes. I. Development of an on-line sample preparation liquid chromatography technique and mass spectroscopic detection of 6beta-hydroxytestosterone. Author(s): Friedrich G, Rose T, Rissler K. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 January 25; 784(1): 49-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504182&dopt=Abstract

•

Development and method validation for testosterone and epitestosterone in human urine samples by liquid chromatography applications. Author(s): Gonzalo-Lumbreras R, Pimentel-Trapero D, Izquierdo-Hornillos R. Source: Journal of Chromatographic Science. 2003 May-June; 41(5): 261-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841955&dopt=Abstract

•

Development of models to predict anabolic response to testosterone administration in healthy young men. Author(s): Woodhouse LJ, Reisz-Porszasz S, Javanbakht M, Storer TW, Lee M, Zerounian H, Bhasin S. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 May; 284(5): E1009-17. Epub 2003 January 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517741&dopt=Abstract

•

Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men. Author(s): Gardner-Thorpe D, O'Hagen C, Young I, Lewis SJ. Source: European Journal of Clinical Nutrition. 2003 January; 57(1): 100-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548304&dopt=Abstract

76

Testosterone

•

Differential anabolic effects of testosterone and amino acid feeding in older men. Author(s): Ferrando AA, Sheffield-Moore M, Paddon-Jones D, Wolfe RR, Urban RJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 January; 88(1): 35862. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519877&dopt=Abstract

•

Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men. Author(s): Van Pottelbergh I, Braeckman L, De Bacquer D, De Backer G, Kaufman JM. Source: Atherosclerosis. 2003 January; 166(1): 95-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482555&dopt=Abstract

•

Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. Author(s): Bartsch G, Rittmaster RS, Klocker H. Source: World Journal of Urology. 2002 April; 19(6): 413-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022710&dopt=Abstract

•

Disappearance of the Brugada-type electrocardiogram after surgical castration: a role for testosterone and an explanation for the male preponderance. Author(s): Matsuo K, Akahoshi M, Seto S, Yano K. Source: Pacing and Clinical Electrophysiology : Pace. 2003 July; 26(7 Pt 1): 1551-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914638&dopt=Abstract

•

Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Author(s): Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD. Source: Clinical Endocrinology. 2003 June; 58(6): 710-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780747&dopt=Abstract

•

Do testosterone levels relate to aggression in elderly men with dementia? Author(s): Orengo C, Kunik ME, Molinari V, Wristers K, Yudofsky SC. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Spring; 14(2): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983790&dopt=Abstract

•

Effect of androstenedione ingestion on plasma testosterone in young women; a dietary supplement with potential health risks. Author(s): Kicman AT, Bassindale T, Cowan DA, Dale S, Hutt AJ, Leeds AR. Source: Clinical Chemistry. 2003 January; 49(1): 167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507974&dopt=Abstract

Studies

77

•

Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men. Author(s): Fogari R, Preti P, Derosa G, Marasi G, Zoppi A, Rinaldi A, Mugellini A. Source: European Journal of Clinical Pharmacology. 2002 June; 58(3): 177-80. Epub 2002 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107602&dopt=Abstract

•

Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. Author(s): Khosla S, Atkinson EJ, Dunstan CR, O'Fallon WM. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 1550-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932280&dopt=Abstract

•

Effect of fatty acids on estradiol and testosterone binding to whole DU-145 prostate cells. Author(s): Prinsloo SE, van Aswegen CH. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2002 April; 66(4): 41925. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054912&dopt=Abstract

•

Effect of growth hormone (GH) and/or testosterone replacement on the prostate in GH-deficient adult patients. Author(s): Colao A, Di Somma C, Spiezia S, Filippella M, Pivonello R, Lombardi G. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 January; 88(1): 8894. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519835&dopt=Abstract

•

Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Author(s): Gonzales GF, Cordova A, Vega K, Chung A, Villena A, Gonez C, Castillo S. Source: Andrologia. 2002 December; 34(6): 367-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472620&dopt=Abstract

•

Effect of low-dose testosterone treatment on androgen regulated proteins prostate specific antigen and sex hormone binding globulin in short prepubertal boys: lack of initiation of puberty. Author(s): Gupta MK, Brown DC, Faiman C, Kelnar CJ, Wu FC. Source: J Pediatr Endocrinol Metab. 2003 January; 16(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585341&dopt=Abstract

78

Testosterone

•

Effect of methyl testosterone administration on plasma viscosity in postmenopausal women. Author(s): Basaria S, Nguyen T, Rosenson RS, Dobs AS. Source: Clinical Endocrinology. 2002 August; 57(2): 209-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153599&dopt=Abstract

•

Effect of testosterone on the apneic threshold in women during NREM sleep. Author(s): Zhou XS, Rowley JA, Demirovic F, Diamond MP, Badr MS. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 January; 94(1): 101-7. Epub 2002 September 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391093&dopt=Abstract

•

Effective testosterone suppression for patients with prostate cancer: is there a best castration? Author(s): Oefelein MG, Resnick MI. Source: Urology. 2003 August; 62(2): 207-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893320&dopt=Abstract

•

Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia. Author(s): Adamopoulos DA, Pappa A, Billa E, Nicopoulou S, Koukkou E, Michopoulos J. Source: Fertility and Sterility. 2003 October; 80(4): 914-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556812&dopt=Abstract

•

Effects of androstenedione administration on epitestosterone metabolism in men. Author(s): Catlin DH, Leder BZ, Ahrens BD, Hatton CK, Finkelstein JS. Source: Steroids. 2002 June; 67(7): 559-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996927&dopt=Abstract

•

Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia. Author(s): Roehrborn CG, Lee M, Meehan A, Waldstreicher J; PLESS Study Group. Source: Urology. 2003 November; 62(5): 894-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14624915&dopt=Abstract

•

Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulinlike growth factor 1 responses to acute resistance exercise. Author(s): Youl Kang H, Hwan Kim S, Jun Lee W, Byrne HK. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2002 May; 16(2): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991768&dopt=Abstract

Studies

79

•

Effects of intravenous cocaine and cigarette smoking on luteinizing hormone, testosterone, and prolactin in men. Author(s): Mendelson JH, Sholar MB, Mutschler NH, Jaszyna-Gasior M, Goletiani NV, Siegel AJ, Mello NK. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 October; 307(1): 339-48. Epub 2003 July 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893845&dopt=Abstract

•

Effects of oral androstenedione administration on serum testosterone and estradiol levels in postmenopausal women. Author(s): Leder BZ, Leblanc KM, Longcope C, Lee H, Catlin DH, Finkelstein JS. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466335&dopt=Abstract

•

Effects of testosterone administration on fat distribution, insulin sensitivity, and atherosclerosis progression. Author(s): Bhasin S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003; 37 Suppl 2: S142-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942389&dopt=Abstract

•

Effects of testosterone and 17-beta-estradiol on TNF-alpha-induced E-selectin and VCAM-1 expression in endothelial cells. Analysis of the underlying receptor pathways. Author(s): Zhang X, Wang LY, Jiang TY, Zhang HP, Dou Y, Zhao JH, Zhao H, Qiao ZD, Qiao JT. Source: Life Sciences. 2002 May 24; 71(1): 15-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020745&dopt=Abstract

•

Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: a randomized controlled trial. Author(s): Lambert CP, Sullivan DH, Freeling SA, Lindquist DM, Evans WJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2100-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994348&dopt=Abstract

•

Effects of testosterone replacement and/or resistance training on interleukin-6, tumor necrosis factor alpha, and leptin in elderly men ingesting megestrol acetate: a randomized controlled trial. Author(s): Lambert CP, Sullivan DH, Evans WJ. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 February; 58(2): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586855&dopt=Abstract

80

Testosterone

•

Effects of the testosterone metabolite dihydrotestosterone and 5 alpha-androstan-3 alpha,17 beta-diol on very long chain fatty acid metabolism in Xadrenoleukodystrophic fibroblasts. Author(s): Petroni A, Blasevich M, Uziel G. Source: Life Sciences. 2003 August 8; 73(12): 1567-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865096&dopt=Abstract

•

Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. Author(s): Kenny AM, Bellantonio S, Gruman CA, Acosta RD, Prestwood KM. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 May; 57(5): M321-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983727&dopt=Abstract

•

Effects of transdermal testosterone on lipids and vascular reactivity in older men with low bioavailable testosterone levels. Author(s): Kenny AM, Prestwood KM, Gruman CA, Fabregas G, Biskup B, Mansoor G. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 July; 57(7): M460-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084809&dopt=Abstract

•

Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men. Author(s): Wolf OT, Kirschbaum C. Source: Hormones and Behavior. 2002 May; 41(3): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971659&dopt=Abstract

•

Estimating the contribution of the prostate to blood dihydrotestosterone. Author(s): Toorians AW, Kelleher S, Gooren LJ, Jimenez M, Handelsman DJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5207-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602751&dopt=Abstract

•

Evaluation of assays available to measure free testosterone. Author(s): Morley JE, Patrick P, Perry HM 3rd. Source: Metabolism: Clinical and Experimental. 2002 May; 51(5): 554-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979385&dopt=Abstract

•

Evaluation of high-dose estrogen and high-dose estrogen plus methyltestosterone treatment on cognitive task performance in postmenopausal women. Author(s): Wisniewski AB, Nguyen TT, Dobs AS. Source: Hormone Research. 2002; 58(3): 150-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218381&dopt=Abstract

Studies

81

•

Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, Testim, compared to AndroGel. Author(s): Marbury T, Hamill E, Bachand R, Sebree T, Smith T. Source: Biopharmaceutics & Drug Disposition. 2003 April; 24(3): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673669&dopt=Abstract

•

Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19nortestosterone in hypogonadal men. Author(s): Anderson RA, Wallace AM, Sattar N, Kumar N, Sundaram K. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2784-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788888&dopt=Abstract

•

Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men. Author(s): O'Connor DB, Archer J, Hair WM, Wu FC. Source: Physiology & Behavior. 2002 April 1; 75(4): 557-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062320&dopt=Abstract

•

Failure to maintain the suppressed level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. Author(s): Kinouchi T, Maeda O, Ono Y, Meguro N, Kuroda M, Usami M. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2002 June; 9(6): 359-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110102&dopt=Abstract

•

Final height outcome and value of height prediction in boys with constitutional delay in growth and adolescence treated with intramuscular testosterone 125 mg per month for 3 months. Author(s): Kelly BP, Paterson WF, Donaldson MD. Source: Clinical Endocrinology. 2003 March; 58(3): 267-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608930&dopt=Abstract

•

Four cardiac hormones increase circulating concentrations of luteinizing hormone and testosterone. Author(s): Vesely DL, San Miguel GI, Hassan L, Gower WR Jr, Schocken DD. Source: Endocrine. 2002 March; 17(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041917&dopt=Abstract

82

Testosterone

•

Free testosterone plasma levels are negatively associated with the intima-media thickness of the common carotid artery in overweight and obese glucose-tolerant young adult men. Author(s): De Pergola G, Pannacciulli N, Ciccone M, Tartagni M, Rizzon P, Giorgino R. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 July; 27(7): 803-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821965&dopt=Abstract

•

Gender differences in the validity of testosterone measured in saliva by immunoassay. Author(s): Shirtcliff EA, Granger DA, Likos A. Source: Hormones and Behavior. 2002 August; 42(1): 62-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191648&dopt=Abstract

•

Gender moderates the relationship between testosterone and marital interaction. Author(s): Cohan CL, Booth A, Granger DA. Source: Journal of Family Psychology : Jfp : Journal of the Division of Family Psychology of the American Psychological Association (Division 43). 2003 March; 17(1): 29-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666461&dopt=Abstract

•

Gene-drug interaction: additive influence of mutant APOA1 and testosterone on plasma HDL-cholesterol. Author(s): Keyhan G, Rosset J, Wang J, Miller D, McManus R, Hegele RA. Source: Clinical Biochemistry. 2002 July; 35(5): 341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270762&dopt=Abstract

•

Gonadotropin-secreting pituitary tumor associated with hypersecretion of testosterone and hypogonadism after hypophysectomy. Author(s): Dizon MN, Vesely DL. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2002 May-June; 8(3): 225-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113637&dopt=Abstract

•

Health related quality of life using serum testosterone as the trigger to re-dose long acting depot luteinizing hormone-releasing hormone agonists in patients with prostate cancer. Author(s): Oefelein MG. Source: The Journal of Urology. 2003 January; 169(1): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478147&dopt=Abstract

Studies

83

•

Higher testosterone dose impairs sperm suppression induced by a combined androgen-progestin regimen. Author(s): Meriggiola MC, Costantino A, Bremner WJ, Morselli-Labate AM. Source: Journal of Andrology. 2002 September-October; 23(5): 684-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185103&dopt=Abstract

•

HIV and testosterone therapy. Author(s): Hengge U. Source: The Lancet Infectious Diseases. 2003 April; 3(4): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679258&dopt=Abstract

•

Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex. Author(s): Steier JA, Ulstein M, Myking OL. Source: Obstetrics and Gynecology. 2002 September; 100(3): 552-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220777&dopt=Abstract

•

Identification and characterization of a novel testosterone-regulated prominin-like gene in the rat ventral prostate. Author(s): Zhang Q, Haleem R, Cai X, Wang Z. Source: Endocrinology. 2002 December; 143(12): 4788-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446606&dopt=Abstract

•

Immunoassays for testosterone in women: better than a guess? Author(s): Herold DA, Fitzgerald RL. Source: Clinical Chemistry. 2003 August; 49(8): 1250-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881438&dopt=Abstract

•

Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men. Author(s): Berg G, Schreier L, Geloso G, Otero P, Nagelberg A, Levalle O. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 February; 34(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972293&dopt=Abstract

•

Important effect of food on the bioavailability of oral testosterone undecanoate. Author(s): Bagchus WM, Hust R, Maris F, Schnabel PG, Houwing NS. Source: Pharmacotherapy. 2003 March; 23(3): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627930&dopt=Abstract

84

Testosterone

•

In regard to Padula et al., normalization of serum testosterone levels in patients treated with neoadjuvant hormonal therapy and three-dimensional conformal radiotherapy for prostate cancer. IJROBP 2002;52: 439-443. Author(s): Dearnaley DP, Norman AR, Shahidi M. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 November 1; 54(3): 981; Author Reply 981. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377353&dopt=Abstract

•

Inhibin B, follicle stimulating hormone, luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relation to age and stage of puberty. Author(s): Chada M, Prusa R, Bronsky J, Kotaska K, Sidlova K, Pechova M, Lisa L. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2003; 52(1): 4551. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625806&dopt=Abstract

•

Inhibition and activation of the human liver microsomal and human cytochrome P450 3A4 metabolism of testosterone by deployment-related chemicals. Author(s): Usmani KA, Rose RL, Hodgson E. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 April; 31(4): 384-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642463&dopt=Abstract

•

Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation. Author(s): Rolf C, Knie U, Lemmnitz G, Nieschlag E. Source: Clinical Endocrinology. 2002 May; 56(5): 637-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030915&dopt=Abstract

•

Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men. Author(s): Roy TA, Blackman MR, Harman SM, Tobin JD, Schrager M, Metter EJ. Source: American Journal of Physiology. Endocrinology and Metabolism. 2002 August; 283(2): E284-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110533&dopt=Abstract

•

Intraoperative testosterone assay for virilizing ovarian tumor topographic assessment: report of a Leydig cell tumor of the ovary in a premenopausal woman with an adrenal incidentaloma. Author(s): Regnier C, Bennet A, Malet D, Guez T, Plantavid M, Rochaix P, Monrozies X, Louvet JP, Caron P. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 July; 87(7): 3074-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107203&dopt=Abstract

Studies

85

•

Inverse relationship between total testosterone and anti-oxidized low density lipoprotein antibody levels in ageing males. Author(s): Barud W, Palusinski R, Beltowski J, Wojcicka G. Source: Atherosclerosis. 2002 October; 164(2): 283-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12204799&dopt=Abstract

•

Investigation of a novel preparation of testosterone decanoate in men: pharmacokinetics and spermatogenic suppression with etonogestrel implants. Author(s): Anderson RA, Zhu H, Cheng L, Baird DT. Source: Contraception. 2002 November; 66(5): 357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443967&dopt=Abstract

•

Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone. Author(s): Anderson RA, Van Der Spuy ZM, Dada OA, Tregoning SK, Zinn PM, Adeniji OA, Fakoya TA, Smith KB, Baird DT. Source: Human Reproduction (Oxford, England). 2002 November; 17(11): 2869-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407041&dopt=Abstract

•

In-vitro effects of FSH and testosterone withdrawal on caspase activation and DNA fragmentation in different cell types of human seminiferous epithelium. Author(s): Tesarik J, Martinez F, Rienzi L, Iacobelli M, Ubaldi F, Mendoza C, Greco E. Source: Human Reproduction (Oxford, England). 2002 July; 17(7): 1811-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093844&dopt=Abstract

•

Is there a role for testosterone therapy in premenopausal women? Author(s): Shifren JL. Source: Menopause (New York, N.Y.). 2003 September-October; 10(5): 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501596&dopt=Abstract

•

Is there any relation between serum levels of total testosterone and the severity of erectile dysfunction? Author(s): Rhoden EL, Teloken C, Mafessoni R, Souto CA. Source: International Journal of Impotence Research : Official Journal of the International Society for Impotence Research. 2002 June; 14(3): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058243&dopt=Abstract

•

Knowledge about low testosterone in older men. Author(s): Tariq SH. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 April; 58(4): 382-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663703&dopt=Abstract

86

Testosterone

•

Levels of testosterone, allopregnanolone and homocysteine in severe hypothyroidism. Author(s): Bicikova M, Tallova J, Stanicka S, Hill M, Vondra K, Hampl R. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 October; 40(10): 1024-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476942&dopt=Abstract

•

Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. Author(s): Gonzalo IT, Swerdloff RS, Nelson AL, Clevenger B, Garcia R, Berman N, Wang C. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3562-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161475&dopt=Abstract

•

Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio. Author(s): Holm M, Rajpert-De Meyts E, Andersson AM, Skakkebaek NE. Source: The Journal of Pathology. 2003 March; 199(3): 378-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579540&dopt=Abstract

•

Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. Author(s): Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 5001-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414864&dopt=Abstract

•

Low serum testosterone level predicts worse response to endocrine therapy in Japanese patients with metastatic prostate cancer. Author(s): Furuya Y, Nozaki T, Nagakawa O, Fuse H. Source: Endocrine Journal. 2002 February; 49(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008754&dopt=Abstract

•

Maintenance of testosterone status in fitness joggers after increased training mileage. Author(s): White LJ, Dressendorfer RH, Ferguson MA, Wade CE. Source: European Journal of Applied Physiology. 2002 April; 86(6): 498-502. Epub 2002 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944097&dopt=Abstract

Studies

87

•

Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies. Author(s): Chatterjee R, Kottaridis PD, McGarrigle HH, Linch DC. Source: Bone Marrow Transplantation. 2002 April; 29(7): 607-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979311&dopt=Abstract

•

Many questions, few answers for testosterone replacement therapy. Author(s): Vastag B. Source: Jama : the Journal of the American Medical Association. 2003 February 26; 289(8): 971-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597734&dopt=Abstract

•

Megestrol acetate to correct the nutritional status in an adolescent with growth hormone deficiency: Increase of appetite and body weight but only by increase of body water and fat mass followed by profound cortisol and testosterone depletion. Author(s): Schmid I, Stachel DK, Freudenberg S, Schmitt M, Schuster F, Haas RJ. Source: Klinische Padiatrie. 2002 March-April; 214(2): 54-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972310&dopt=Abstract

•

Megestrol acetate-induced weight gain does not negatively affect blood lipids in elderly men: effects of resistance training and testosterone replacement. Author(s): Lambert CP, Sullivan DH, Evans WJ. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 644-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865481&dopt=Abstract

•

Men in committed, romantic relationships have lower testosterone. Author(s): Burnham TC, Chapman JF, Gray PB, McIntyre MH, Lipson SF, Ellison PT. Source: Hormones and Behavior. 2003 August; 44(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129483&dopt=Abstract

•

Middle-aged men secrete less testosterone at night than young healthy men. Author(s): Luboshitzky R, Shen-Orr Z, Herer P. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3160-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843160&dopt=Abstract

•

Monthly patterns of testosterone and behavior in prospective fathers. Author(s): Hirschenhauser K, Frigerio D, Grammer K, Magnusson MS. Source: Hormones and Behavior. 2002 September; 42(2): 172-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367570&dopt=Abstract

88

Testosterone

•

Mumps virus decreases testosterone production and gamma interferon-induced protein 10 secretion by human leydig cells. Author(s): Le Goffic R, Mouchel T, Ruffault A, Patard JJ, Jegou B, Samson M. Source: Journal of Virology. 2003 March; 77(5): 3297-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584353&dopt=Abstract

•

New testosterone therapy OK'd. Author(s): Leibovich M. Source: Posit Living. 2000 July; 9(6): 21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492015&dopt=Abstract

•

Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells. Author(s): Wolf R, Schonfelder G, Paul M, Blume-Peytavi U. Source: Journal of Molecular Medicine (Berlin, Germany). 2003 February; 81(2): 110-7. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601527&dopt=Abstract

•

No relationship between testosterone levels and depressive symptoms in aging men. Author(s): Kaneda Y, Fujii A. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 November; 17(7): 411-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547308&dopt=Abstract

•

Oestrogen, bones and men: when testosterone just isn't enough. Author(s): Khosla S. Source: Clinical Endocrinology. 2002 March; 56(3): 291-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940038&dopt=Abstract

•

Oligospermia due to partial maturation arrest responds to low dose estrogentestosterone combination therapy resulting in live-birth: a case report. Author(s): Sah P. Source: Asian Journal of Andrology. 2002 December; 4(4): 307-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508135&dopt=Abstract

•

On call. My wife and I are both 62 and healthy. She started taking Prempro during her menopause eight years ago but has now decided to stop the hormones. I began taking DHEA five years ago, but I switched to AndroGel when my doctor gave me a prescription last year. Should I stay on AndroGel, go back to DHEA, or stop hormones? Author(s): Simon HB. Source: Harvard Men's Health Watch. 2003 January; 7(6): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543598&dopt=Abstract

Studies

89

•

Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men. Author(s): Kinniburgh D, Zhu H, Cheng L, Kicman AT, Baird DT, Anderson RA. Source: Human Reproduction (Oxford, England). 2002 June; 17(6): 1490-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042267&dopt=Abstract

•

Oral testosterone replacement in Korean patients with PADAM. Author(s): Hong JH, Ahn TY. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2002 March; 5(1): 52-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040976&dopt=Abstract

•

Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. Author(s): Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 618-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865477&dopt=Abstract

•

Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency. Author(s): Park NC, Yan BQ, Chung JM, Lee KM. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2003 June; 6(2): 86-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898792&dopt=Abstract

•

Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone. Author(s): Kalinchenko SY, Kozlov GI, Gontcharov NP, Katsiya GV. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2003 June; 6(2): 94-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898793&dopt=Abstract

•

Patient satisfaction with testosterone supplementation for the treatment of erectile dysfunction. Author(s): Monga M, Kostelec M, Kamarei M. Source: Archives of Andrology. 2002 November-December; 48(6): 433-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425760&dopt=Abstract

90

Testosterone

•

Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men. Author(s): Rolf C, Kemper S, Lemmnitz G, Eickenberg U, Nieschlag E. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 May; 146(5): 673-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980623&dopt=Abstract

•

Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women. Author(s): Wren BG, Day RO, McLachlan AJ, Williams KM. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 104-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841880&dopt=Abstract

•

Pharmacokinetics, safety and tolerability of three dosage regimens of buccal adhesive testosterone tablets in healthy men suppressed with leuprorelin. Author(s): Baisley KJ, Boyce MJ, Bukofzer S, Pradhan R, Warrington SJ. Source: The Journal of Endocrinology. 2002 December; 175(3): 813-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475391&dopt=Abstract

•

Physiological testosterone replacement and arterial endothelial function in men. Author(s): Sader MA, Griffiths KA, Skilton MR, Wishart SM, Handelsman DJ, Celermajer DS. Source: Clinical Endocrinology. 2003 July; 59(1): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807505&dopt=Abstract

•

Plasma testosterone levels in patients with combat-related posttraumatic stress disorder. Author(s): Spivak B, Maayan R, Mester R, Weizman A. Source: Neuropsychobiology. 2003; 47(2): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707485&dopt=Abstract

•

Population variation in age-related decline in male salivary testosterone. Author(s): Ellison PT, Bribiescas RG, Bentley GR, Campbell BC, Lipson SF, Panter-Brick C, Hill K. Source: Human Reproduction (Oxford, England). 2002 December; 17(12): 3251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456632&dopt=Abstract

•

Precocious puberty secondary to topical testosterone exposure. Author(s): Franklin SL, Geffner ME. Source: J Pediatr Endocrinol Metab. 2003 January; 16(1): 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585348&dopt=Abstract

Studies

91

•

Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. Author(s): Amory JK, Chansky HA, Chansky KL, Camuso MR, Hoey CT, Anawalt BD, Matsumoto AM, Bremner WJ. Source: Journal of the American Geriatrics Society. 2002 October; 50(10): 1698-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366624&dopt=Abstract

•

Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. Author(s): Massengill JC, Sun L, Moul JW, Wu H, McLeod DG, Amling C, Lance R, Foley J, Sexton W, Kusuda L, Chung A, Soderdahl D, Donahue T. Source: The Journal of Urology. 2003 May; 169(5): 1670-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686805&dopt=Abstract

•

Production rates of testosterone and of dihydrotestosterone in female pattern hair loss. Author(s): Vierhapper H, Maier H, Nowotny P, Waldhausl W. Source: Metabolism: Clinical and Experimental. 2003 July; 52(7): 927-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870172&dopt=Abstract

•

Prolactin, testosterone and cortisol as possible markers of changes in cardiovascular function associated with urbanization. Author(s): Huisman HW, van Rooyen JM, Malan NT, Eloff FC, Malan L, Laubscher PJ, Schutte AE. Source: Journal of Human Hypertension. 2002 December; 16(12): 829-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522463&dopt=Abstract

•

Prostate volume and growth in testosterone-substituted hypogonadal men are dependent on the CAG repeat polymorphism of the androgen receptor gene: a longitudinal pharmacogenetic study. Author(s): Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 May; 88(5): 2049-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727953&dopt=Abstract

•

Prostate-specific antigen changes in hypogonadal men treated with testosterone replacement. Author(s): Gerstenbluth RE, Maniam PN, Corty EW, Seftel AD. Source: Journal of Andrology. 2002 November-December; 23(6): 922-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399540&dopt=Abstract

92

Testosterone

•

Rapid HPLC-electrospray tandem mass spectrometric assay for urinary testosterone and dihydrotestosterone glucuronides from patients with benign prostate hyperplasia. Author(s): Choi MH, Kim JN, Chung BC. Source: Clinical Chemistry. 2003 February; 49(2): 322-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560362&dopt=Abstract

•

Reduced production rates of testosterone and dihydrotestosterone in healthy men treated with rosiglitazone. Author(s): Vierhapper H, Nowotny P, Waldhausl W. Source: Metabolism: Clinical and Experimental. 2003 February; 52(2): 230-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601638&dopt=Abstract

•

Reduced testosterone levels in human immunodeficiency virus-infected women with weight loss and low weight. Author(s): Huang JS, Wilkie SJ, Dolan S, Gallafent JH, Aliabadi N, Sullivan MP, Grinspoon S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 February 15; 36(4): 499-506. Epub 2003 January 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567309&dopt=Abstract

•

Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity. Author(s): Okun MS, McDonald WM, DeLong MR. Source: Archives of Neurology. 2002 May; 59(5): 807-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020264&dopt=Abstract

•

Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. Author(s): Cermik D, Selam B, Taylor HS. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 January; 88(1): 23843. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519859&dopt=Abstract

•

Relationship between REM sleep and testosterone secretion in older men. Author(s): Penev P, Spiegel K, L'Hermite-Baleriaux M, Schneider R, Van Cauter E. Source: Annales D'endocrinologie. 2003 April; 64(2): 157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773954&dopt=Abstract

Studies

93

•

Requirement of c-jun for testosterone-induced sensitization to N-(4hydroxyphenyl)retinamide-induced apoptosis. Author(s): Shimada K, Nakamura M, Ishida E, Kishi M, Konishi N. Source: Molecular Carcinogenesis. 2003 March; 36(3): 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619033&dopt=Abstract

•

Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men. Author(s): Roubenoff R, Grinspoon S, Skolnik PR, Tchetgen E, Abad L, Spiegelman D, Knox T, Gorbach S. Source: American Journal of Physiology. Endocrinology and Metabolism. 2002 July; 283(1): E138-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067854&dopt=Abstract

•

Role of testosterone, estradiol, and insulin in diet- and exercise-induced reductions in serum-stimulated prostate cancer cell growth in vitro. Author(s): Tymchuk CN, Barnard RJ, Ngo TH, Aronson WJ. Source: Nutrition and Cancer. 2002; 42(1): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235642&dopt=Abstract

•

Safety profile of transdermal testosterone therapy in women. Author(s): Shifren JL, Mazer NA. Source: American Journal of Obstetrics and Gynecology. 2003 September; 189(3): 898-9; Author Reply 899. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560750&dopt=Abstract

•

Salivary testosterone and EEG spectra of 9- to 11-year-old male children. Author(s): Poblano A, Rothenberg SJ, Fonseca ME, Cruz ML, Flores T, Zarco I. Source: Developmental Neuropsychology. 2003; 23(3): 375-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740191&dopt=Abstract

•

Salivary testosterone is related to both handedness and degree of linguistic lateralization in normal women. Author(s): Gadea M, Gomez C, Gonzalez-Bono E, Salvador A, Espert R. Source: Psychoneuroendocrinology. 2003 April; 28(3): 274-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573296&dopt=Abstract

•

Seasonal variation of testosterone and waist to hip ratio in men: the Tromso study. Author(s): Svartberg J, Jorde R, Sundsfjord J, Bonaa KH, Barrett-Connor E. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3099104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843149&dopt=Abstract

94

Testosterone

•

Second to fourth digit ratio, testosterone and perceived male dominance. Author(s): Neave N, Laing S, Fink B, Manning JT. Source: Proceedings of the Royal Society of London. Series B. Biological Sciences. 2003 October 22; 270(1529): 2167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561281&dopt=Abstract

•

Self-rated aggression related to serum testosterone and platelet MAO activity in female patients with the fibromyalgia syndrome. Author(s): Prochazka H, Anderberg UM, Oreland L, Knorring LV, Agren H. Source: World J Biol Psychiatry. 2003 January; 4(1): 35-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582976&dopt=Abstract

•

Serum androgen bioactivity during 5alpha-dihydrotestosterone treatment in elderly men. Author(s): Raivio T, Tapanainen JS, Kunelius P, Janne OA. Source: Journal of Andrology. 2002 November-December; 23(6): 919-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399539&dopt=Abstract

•

Serum inhibin B, FSH, LH and testosterone levels before and after human chorionic gonadotropin stimulation in prepubertal boys with cryptorchidism. Author(s): Christiansen P, Andersson AM, Skakkebaek NE, Juul A. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 July; 147(1): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088925&dopt=Abstract

•

Serum testosterone suppression and potential for agonistic stimulation during chronic treatment with monthly and 3-month depot formulations of leuprolide acetate for advanced prostate cancer. Author(s): Sharifi R, Browneller R; Leuprolide Study Group. Source: The Journal of Urology. 2002 September; 168(3): 1001-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187208&dopt=Abstract

•

Sex- and age-related changes in epitestosterone in relation to pregnenolone sulfate and testosterone in normal subjects. Author(s): Havlikova H, Hill M, Hampl R, Starka L. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2225-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994368&dopt=Abstract

•

Sex, drugs and arrhythmia: are gender differences in risk of torsades de pointes simply a matter of testosterone? Author(s): James AF, Hancox JC. Source: Cardiovascular Research. 2003 January; 57(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504807&dopt=Abstract

Studies

95

•

Sexual activity and plasma testosterone levels in hypertensive males. Author(s): Fogari R, Zoppi A, Preti P, Rinaldi A, Marasi G, Vanasia A, Mugellini A. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 March; 15(3): 217-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939610&dopt=Abstract

•

Short boys treated with growth hormone show normal progression of testicular size and achieve normal serum testosterone concentrations. Author(s): Ankarberg-Lindgren C, Norjavaara E, Wikland KA. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 May; 146(5): 681-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980624&dopt=Abstract

•

Should the nonaromatizable androgen dihydrotestosterone be considered as an alternative to testosterone in the treatment of the andropause? Author(s): Wang C, Swerdloff RS. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 1462-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932265&dopt=Abstract

•

Significant ethnic variation in total and free testosterone concentration. Author(s): Heald AH, Ivison F, Anderson SG, Cruickshank K, Laing I, Gibson JM. Source: Clinical Endocrinology. 2003 March; 58(3): 262-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608929&dopt=Abstract

•

Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men. Author(s): Brill KT, Weltman AL, Gentili A, Patrie JT, Fryburg DA, Hanks JB, Urban RJ, Veldhuis JD. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5649-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466367&dopt=Abstract

•

Smoking, sperm quality and testosterone level. Author(s): James WH. Source: Human Reproduction (Oxford, England). 2002 December; 17(12): 3275-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456635&dopt=Abstract

96

Testosterone

•

Status, testosterone, and human intellectual performance: stereotype threat as status concern. Author(s): Josephs RA, Newman ML, Brown RP, Beer JM. Source: Psychological Science : a Journal of the American Psychological Society / Aps. 2003 March; 14(2): 158-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661678&dopt=Abstract

•

Stephacidin A and B: two structurally novel, selective inhibitors of the testosteronedependent prostate LNCaP cells. Author(s): Qian-Cutrone J, Huang S, Shu YZ, Vyas D, Fairchild C, Menendez A, Krampitz K, Dalterio R, Klohr SE, Gao Q. Source: Journal of the American Chemical Society. 2002 December 11; 124(49): 14556-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465964&dopt=Abstract

•

Suppression of prostate tumor growth by U19, a novel testosterone-regulated apoptosis inducer. Author(s): Xiao W, Zhang Q, Jiang F, Pins M, Kozlowski JM, Wang Z. Source: Cancer Research. 2003 August 1; 63(15): 4698-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907652&dopt=Abstract

•

Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception. Author(s): Anderson RA, Kinniburgh D, Baird DT. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3640-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161488&dopt=Abstract

•

Synergistic effects of testosterone and growth hormone on protein metabolism and body composition in prepubertal boys. Author(s): Mauras N, Rini A, Welch S, Sager B, Murphy SP. Source: Metabolism: Clinical and Experimental. 2003 August; 52(8): 964-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898459&dopt=Abstract

•

Testosterone “fix”: youth or consequences? Should we treat “male menopause”? Author(s): Utiger RD. Source: Health News. 2003 April; 9(4): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710389&dopt=Abstract

•

Testosterone 17beta-N,N-dimethylglycinate hydrochloride: A prodrug with a potential for nasal delivery of testosterone. Author(s): Hussain AA, Al-Bayatti AA, Dakkuri A, Okochi K, Hussain MA. Source: Journal of Pharmaceutical Sciences. 2002 March; 91(3): 785-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920764&dopt=Abstract

Studies

97

•

Testosterone administration to men increases hepatic lipase activity and decreases HDL and LDL size in 3 wk. Author(s): Herbst KL, Amory JK, Brunzell JD, Chansky HA, Bremner WJ. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 June; 284(6): E1112-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736156&dopt=Abstract

•

Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Author(s): Ortmann J, Prifti S, Bohlmann MK, Rehberger-Schneider S, Strowitzki T, Rabe T. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 April; 16(2): 113-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12012621&dopt=Abstract

•

Testosterone and behavior. Author(s): Morley JE. Source: Clinics in Geriatric Medicine. 2003 August; 19(3): 605-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567011&dopt=Abstract

•

Testosterone and child and adolescent adjustment: the moderating role of parentchild relationships. Author(s): Booth A, Johnson DR, Granger DA, Crouter AC, McHale S. Source: Developmental Psychology. 2003 January; 39(1): 85-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518811&dopt=Abstract

•

Testosterone and comprehensive geriatric assessment in frail elderly men. Author(s): Akishita M, Yamada S, Nishiya H, Sonohara K, Ohni M, Toba K. Source: Journal of the American Geriatrics Society. 2003 September; 51(9): 1324-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919251&dopt=Abstract

•

Testosterone and diurnal rhythmicity of leptin, TNF-alpha and TNF-II receptor in insulin-resistant myotonic dystrophy patients. Author(s): Johansson A, Ahren B, Forsberg H, Olsson T. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 October; 26(10): 1386-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355336&dopt=Abstract

•

Testosterone and estradiol modulate TNF-alpha-induced expression of adhesion molecules in endothelial cells. Author(s): Zhang X, Wang L, Dou Y, Zhao J, Jiang T, Qiao Z, Qiao J. Source: Methods Find Exp Clin Pharmacol. 2002 April; 24(3): 125-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087872&dopt=Abstract

98

Testosterone

•

Testosterone and prolactin are associated with emotional responses to infant cries in new fathers. Author(s): Fleming AS, Corter C, Stallings J, Steiner M. Source: Hormones and Behavior. 2002 December; 42(4): 399-413. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488107&dopt=Abstract

•

Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Author(s): Costello LC, Franklin RB. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 August; 34(8): 417-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198595&dopt=Abstract

•

Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability. Author(s): Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer KS. Source: The Journal of Endocrinology. 2003 September; 178(3): 373-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967330&dopt=Abstract

•

Testosterone cream available at CPS; gel approved by FDA. Author(s): James JS. Source: Aids Treat News. 2000 March 17; (339): 4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870449&dopt=Abstract

•

Testosterone deficiency and mood in aging men: pathogenic and therapeutic interactions. Author(s): Seidman SN. Source: World J Biol Psychiatry. 2003 January; 4(1): 14-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582972&dopt=Abstract

•

Testosterone deficiency in men. Diagnosis and management. Author(s): Allan CA, McLachlan RI. Source: Aust Fam Physician. 2003 June; 32(6): 422-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833767&dopt=Abstract

•

Testosterone deficiency in women: etiologies, diagnosis, and emerging treatments. Author(s): Mazer NA. Source: Int J Fertil Womens Med. 2002 March-April; 47(2): 77-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991434&dopt=Abstract

Studies

99

•

Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. Author(s): Storer TW, Magliano L, Woodhouse L, Lee ML, Dzekov C, Dzekov J, Casaburi R, Bhasin S. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 147885. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679426&dopt=Abstract

•

Testosterone during pregnancy and gender role behavior of preschool children: a longitudinal, population study. Author(s): Hines M, Golombok S, Rust J, Johnston KJ, Golding J; Avon Longitudinal Study of Parents and Children Study Team. Source: Child Development. 2002 November-December; 73(6): 1678-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487486&dopt=Abstract

•

Testosterone for secondary prevention in men with ischaemic heart disease? Author(s): Malkin CJ, Pugh PJ, Jones TH, Channer KS. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 July; 96(7): 521-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881595&dopt=Abstract

•

Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Author(s): Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Source: The American Journal of Psychiatry. 2003 January; 160(1): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505808&dopt=Abstract

•

Testosterone increases in men after a low dose of alcohol. Author(s): Sarkola T, Eriksson CJ. Source: Alcoholism, Clinical and Experimental Research. 2003 April; 27(4): 682-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711931&dopt=Abstract

•

Testosterone increases perceived dominance but not attractiveness in human males. Author(s): Swaddle JP, Reierson GW. Source: Proceedings of the Royal Society of London. Series B. Biological Sciences. 2002 November 22; 269(1507): 2285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495494&dopt=Abstract

•

Testosterone induced priapism in Kallmann's syndrome. Author(s): Shergill IS, Pranesh N, Hamid R, Arya M, Anjum I. Source: The Journal of Urology. 2003 March; 169(3): 1089. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576857&dopt=Abstract

100 Testosterone

•

Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells. Author(s): Hatakeyama H, Nishizawa M, Nakagawa A, Nakano S, Kigoshi T, Uchida K. Source: Febs Letters. 2002 October 23; 530(1-3): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387879&dopt=Abstract

•

Testosterone insufficiency in women: fact or fiction? Author(s): Guay A, Davis SR. Source: World Journal of Urology. 2002 June; 20(2): 106-10. Epub 2002 May 03. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107541&dopt=Abstract

•

Testosterone is a potential augmentor of antioxidant-induced apoptosis in human prostate cancer cells. Author(s): Gunawardena K, Murray DK, Meikle AW. Source: Cancer Detection and Prevention. 2002; 26(2): 105-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102144&dopt=Abstract

•

Testosterone levels in pregnant women correlate with the insulin response during the glucose tolerance test. Author(s): Dokras A, Spaczynski RZ, Behrman HR, Duleba AJ. Source: Fertility and Sterility. 2003 March; 79(3): 492-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620428&dopt=Abstract

•

Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography-mass spectrometry in sera from 116 men, women, and children. Author(s): Taieb J, Mathian B, Millot F, Patricot MC, Mathieu E, Queyrel N, Lacroix I, Somma-Delpero C, Boudou P. Source: Clinical Chemistry. 2003 August; 49(8): 1381-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881456&dopt=Abstract

•

Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Author(s): Katsuno M, Adachi H, Kume A, Li M, Nakagomi Y, Niwa H, Sang C, Kobayashi Y, Doyu M, Sobue G. Source: Neuron. 2002 August 29; 35(5): 843-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372280&dopt=Abstract

•

Testosterone replacement therapy for bone loss prevention in HIV-infected males. Author(s): Clay PG, Lam AI. Source: The Annals of Pharmacotherapy. 2003 April; 37(4): 582-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659619&dopt=Abstract

Studies

101

•

Testosterone replacement therapy restores normal ghrelin in hypogonadal men. Author(s): Pagotto U, Gambineri A, Pelusi C, Genghini S, Cacciari M, Otto B, Castaneda T, Tschop M, Pasquali R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970277&dopt=Abstract

•

Testosterone stimulates proliferation and inhibits interleukin-6 production of normal and hereditary gingival fibromatosis fibroblasts. Author(s): Coletta RD, Reynolds MA, Martelli-Junior H, Graner E, Almeida OP, Sauk JJ. Source: Oral Microbiology and Immunology. 2002 June; 17(3): 186-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030972&dopt=Abstract

•

Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Author(s): Boyanov MA, Boneva Z, Christov VG. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2003 March; 6(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809074&dopt=Abstract

•

Testosterone supplementation therapy for older men: potential benefits and risks. Author(s): Gruenewald DA, Matsumoto AM. Source: Journal of the American Geriatrics Society. 2003 January; 51(1): 101-15; Discussion 115. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534854&dopt=Abstract

•

Testosterone suppression in men with prostate cancer is associated with increased arterial stiffness. Author(s): Dockery F, Bulpitt CJ, Agarwal S, Rajkumar C. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2002 December; 5(4): 216-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630068&dopt=Abstract

•

Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Author(s): Dockery F, Bulpitt CJ, Agarwal S, Donaldson M, Rajkumar C. Source: Clinical Science (London, England : 1979). 2003 February; 104(2): 195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546642&dopt=Abstract

•

Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. Author(s): Kong A, Edmonds P. Source: The Lancet Infectious Diseases. 2002 November; 2(11): 692-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409050&dopt=Abstract

102 Testosterone

•

Testosterone therapy in late-life major depression in males. Author(s): Perry PJ, Yates WR, Williams RD, Andersen AE, MacIndoe JH, Lund BC, Holman TL. Source: The Journal of Clinical Psychiatry. 2002 December; 63(12): 1096-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523867&dopt=Abstract

•

Testosterone therapy in microphallic hypospadias: topical or parenteral? Author(s): Chalapathi G, Rao KL, Chowdhary SK, Narasimhan KL, Samujh R, Mahajan JK. Source: Journal of Pediatric Surgery. 2003 February; 38(2): 221-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596107&dopt=Abstract

•

Testosterone treatment enhances regional brain perfusion in hypogonadal men. Author(s): Azad N, Pitale S, Barnes WE, Friedman N. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3064-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843144&dopt=Abstract

•

Testosterone up-regulates scavenger receptor BI and stimulates cholesterol efflux from macrophages. Author(s): Langer C, Gansz B, Goepfert C, Engel T, Uehara Y, von Dehn G, Jansen H, Assmann G, von Eckardstein A. Source: Biochemical and Biophysical Research Communications. 2002 September 6; 296(5): 1051-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207878&dopt=Abstract

•

Testosterone, 5 alpha-dihydrotestosterone and cortisol in men with and without alcohol-related aggression. Author(s): von der PB, Sarkola T, Seppa K, Eriksson CJ. Source: J Stud Alcohol. 2002 September; 63(5): 518-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380846&dopt=Abstract

•

Testosterone, alcohol, and civil and rough conflict resolution strategies in lesbian couples. Author(s): Baker LA, Pearcey SM, Dabbs JM Jr. Source: Journal of Homosexuality. 2002; 42(4): 77-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243486&dopt=Abstract

•

Testosterone, cytochrome P450, and cardiac hypertrophy. Author(s): Thum T, Borlak J. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2002 October; 16(12): 1537-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374776&dopt=Abstract

Studies

103

•

Testosterone, sexuality and antisocial personality in rapists and child molesters: a pilot study. Author(s): Aromaki AS, Lindman RE, Eriksson CJ. Source: Psychiatry Research. 2002 July 31; 110(3): 239-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127474&dopt=Abstract

•

Testosterone, territoriality, and the 'home advantage'. Author(s): Neave N, Wolfson S. Source: Physiology & Behavior. 2003 February; 78(2): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576125&dopt=Abstract

•

Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Author(s): Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, Storer TW, Casaburi R, Shen R, Bhasin S. Source: American Journal of Physiology. Endocrinology and Metabolism. 2002 July; 283(1): E154-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067856&dopt=Abstract

•

Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Author(s): Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 July; 285(1): E197-205. Epub 2003 April 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670837&dopt=Abstract

•

The association of lower testosterone level with coronary artery disease in postmenopausal women. Author(s): Kaczmarek A, Reczuch K, Majda J, Banasiak W, Ponikowski P. Source: International Journal of Cardiology. 2003 January; 87(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468054&dopt=Abstract

•

The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study. Author(s): Svartberg J, Midtby M, Bonaa KH, Sundsfjord J, Joakimsen RM, Jorde R. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 August; 149(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887292&dopt=Abstract

104 Testosterone

•

The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance. Author(s): Jayagopal V, Kilpatrick ES, Jennings PE, Hepburn DA, Atkin SL. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 152833. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679434&dopt=Abstract

•

The challenges of testosterone deficiency. Uncovering the problem, evaluating the role of therapy. Author(s): MacIndoe JH. Source: Postgraduate Medicine. 2003 October; 114(4): 51-3, 57-8, 61-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587207&dopt=Abstract

•

The circalunar cycle of salivary testosterone and the visual-spatial performance. Author(s): Celec P, Ostatnikova D, Putz Z, Kudela M. Source: Bratisl Lek Listy. 2002; 103(2): 59-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12061023&dopt=Abstract

•

The effect of testosterone on regional blood flow in prepubertal anaesthetized pigs. Author(s): Molinari C, Battaglia A, Grossini E, Mary DA, Vassanelli C, Vacca G. Source: The Journal of Physiology. 2002 August 15; 543(Pt 1): 365-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181306&dopt=Abstract

•

The effects of one- and two-stage orchiopexy on postoperative serum testosterone levels and testicular volume in adult patients with bilateral nonpalpable testes. Author(s): Sahin C, Artan M, Aksoy Y. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2002 October; 12(5): 327-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470406&dopt=Abstract

•

The effects of testosterone deficiency on male sexual function. Author(s): Kaufman JM, T'Sjoen G. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2002 December; 5(4): 242-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630072&dopt=Abstract

•

The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. Author(s): Kunelius P, Lukkarinen O, Hannuksela ML, Itkonen O, Tapanainen JS. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 146772. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932266&dopt=Abstract

Studies

105

•

The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. Author(s): Kampa M, Papakonstanti EA, Hatzoglou A, Stathopoulos EN, Stournaras C, Castanas E. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2002 September; 16(11): 1429-31. Epub 2002 July 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205037&dopt=Abstract

•

The impact of testosterone imbalance on depression and women's health. Author(s): Rohr UD. Source: Maturitas. 2002 April 15; 41 Suppl 1: S25-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955793&dopt=Abstract

•

The interaction of human and bovine serum proteins with CYP3A in human liver microsomes: inhibition of testosterone 6beta-hydroxylation by albumin, alphaglobulins, alpha(1)-acid glycoprotein and gamma-globulins. Author(s): Matsumoto S, Ding LR, Ishii M, Fischer NE, Inaba T. Source: Toxicology Letters. 2002 November 15; 136(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368055&dopt=Abstract

•

The male contraceptive regimen of testosterone and levonorgestrel significantly increases lean mass in healthy young men in 4 weeks, but attenuates a decrease in fat mass induced by testosterone alone. Author(s): Herbst KL, Anawalt BD, Amory JK, Matsumoto AM, Bremner WJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 116773. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629101&dopt=Abstract

•

The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. Author(s): Gillam MP, Middler S, Freed DJ, Molitch ME. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4447-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364416&dopt=Abstract

•

The relationship between testosterone and route-learning strategies in humans. Author(s): Choi J, Silverman I. Source: Brain and Cognition. 2002 October; 50(1): 116-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372356&dopt=Abstract

106 Testosterone

•

The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity. Author(s): Lasley BL, Santoro N, Randolf JF, Gold EB, Crawford S, Weiss G, McConnell DS, Sowers MF. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3760-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161507&dopt=Abstract

•

The role of dihydrotestosterone in benign prostatic hyperplasia. Author(s): Carson C 3rd, Rittmaster R. Source: Urology. 2003 April; 61(4 Suppl 1): 2-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657354&dopt=Abstract

•

The role of insulin 3, testosterone, Mullerian inhibiting substance and relaxin in rat gubernacular growth. Author(s): Kubota Y, Temelcos C, Bathgate RA, Smith KJ, Scott D, Zhao C, Hutson JM. Source: Molecular Human Reproduction. 2002 October; 8(10): 900-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356938&dopt=Abstract

•

The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. Author(s): Liu PY, Yee B, Wishart SM, Jimenez M, Jung DG, Grunstein RR, Handelsman DJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3605-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915643&dopt=Abstract

•

The testosterone connection. Author(s): Smith S. Source: Kans Nurse. 2003 August; 78(7): 16-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528599&dopt=Abstract

•

The vasodilatory action of testosterone: a potassium-channel opening or a calcium antagonistic action? Author(s): Jones RD, Pugh PJ, Jones TH, Channer KS. Source: British Journal of Pharmacology. 2003 March; 138(5): 733-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642373&dopt=Abstract

•

Thin-layer chromatographic analysis of human CYP3A-catalyzed testosterone 6 betahydroxylation. Author(s): Waxman DJ, Chang TK. Source: Methods in Molecular Biology (Clifton, N.J.). 1998; 107: 153-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14577225&dopt=Abstract

Studies

107

•

Torilin from Torilis japonica, as a new inhibitor of testosterone 5 alpha-reductase. Author(s): Park WS, Son ED, Nam GW, Kim SH, Noh MS, Lee BG, Jang IS, Kim SE, Lee JJ, Lee CH. Source: Planta Medica. 2003 May; 69(5): 459-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802730&dopt=Abstract

•

Transdermal testosterone for women: a new physiological approach for androgen therapy. Author(s): Mazer NA, Shifren JL. Source: Obstetrical & Gynecological Survey. 2003 July; 58(7): 489-500. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832941&dopt=Abstract

•

Transdermal testosterone gel (Cellegy). Author(s): McGriff-Lee NJ. Source: Curr Opin Investig Drugs. 2002 November; 3(11): 1629-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476964&dopt=Abstract

•

Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Author(s): Goldstat R, Briganti E, Tran J, Wolfe R, Davis SR. Source: Menopause (New York, N.Y.). 2003 September-October; 10(5): 390-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501599&dopt=Abstract

•

Treatment of leuprolide-induced depression with intramuscular testosterone: a case report. Author(s): Acta Obstet Gynecol Scand. 2003 Jul;82(7):335-44 Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 341-3. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12790856

•

Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: a phase II study. Author(s): von Eckardstein S, Nieschlag E. Source: Journal of Andrology. 2002 May-June; 23(3): 419-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002444&dopt=Abstract

•

Twenty-one day administration of dienogest reversibly suppresses gonadotropins and testosterone in normal men. Author(s): Meriggiola MC, Bremner WJ, Costantino A, Bertaccini A, Morselli-Labate AM, Huebler D, Kaufmann G, Oettel M, Flamigni C. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2107-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994349&dopt=Abstract

108 Testosterone

•

Unilateral autonomous testicular testosterone production mimicking androgen independent prostate cancer. Author(s): Lavelle M, Schuff KG, Keller FS, Binkert CA, O'Hara M, Fairfax CA, Beer TM. Source: The Journal of Urology. 2002 September; 168(3): 1098-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187234&dopt=Abstract

•

Use of parenteral testosterone prior to hypospadias surgery. Author(s): Luo CC, Lin JN, Chiu CH, Lo FS. Source: Pediatric Surgery International. 2003 April; 19(1-2): 82-4. Epub 2003 March 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721732&dopt=Abstract

•

Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations. Author(s): Rinaldi S, Geay A, Dechaud H, Biessy C, Zeleniuch-Jacquotte A, Akhmedkhanov A, Shore RE, Riboli E, Toniolo P, Kaaks R. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 October; 11(10 Pt 1): 1065-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376508&dopt=Abstract

•

Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period: possible effects of seasons. Author(s): Andersson AM, Carlsen E, Petersen JH, Skakkebaek NE. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 932-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574235&dopt=Abstract

•

What happens to testosterone after prostate radiation monotherapy and does it matter? Author(s): Pickles T, Graham P; Members of the British Columbia Cancer Agency Prostate Cohort Outcomes Initiative. Source: The Journal of Urology. 2002 June; 167(6): 2448-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992055&dopt=Abstract

•

WNT4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy. Author(s): Jordan BK, Shen JH, Olaso R, Ingraham HA, Vilain E. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 September 16; 100(19): 10866-71. Epub 2003 August 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949260&dopt=Abstract

109

CHAPTER 2. NUTRITION AND TESTOSTERONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and testosterone.

Finding Nutrition Studies on Testosterone The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “testosterone” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

110 Testosterone

The following is a typical result when searching for recently indexed consumer information on testosterone: •

“I've heard that testosterone can boost a woman's libido. Is it safe to take male hormones”? Source: Anonymous Harv-Health-Lett. 1998 May; 23(7): 7 1052-1577

•

I've heard that scientists are looking at testosterone injections as a form of male contraception. How does adding testosterone make a man infertile? Source: Atkinson, H G Health-News. 2000 September; 6(9): 10 1081-5880

•

Testosterone and the aging ovary. Source: Anonymous Harv-Womens-Health-Watch. 1998 December; 6(4): 1 1070-910X

•

Testosterone for women? Source: Anonymous Harv-Mens-Health-Watch. 2000 October; 5(3): 7-8 1089-1102

The following information is typical of that found when using the “Full IBIDS Database” to search for “testosterone” (or a synonym): •

17beta-estradiol, progesterone and testosterone concentrations in cystic fluids and response to GnRH treatment after emptying of ovarian cysts in dairy cows. Author(s): Institute of Obstetrics and Veterinary Gynaecology, University of Milan, Italy. Source: Cairoli, F Vigo, D Battocchio, M Faustini, M Veronesi, M C Maffeo, G ReprodDomest-Anim. 2002 October; 37(5): 294-8 0936-6768

•

Activational effects of testosterone on cognitive function in men. Author(s): Department of Endocrinology, Manchester Royal Infirmary, University of Manchester, Manchester M13 9WL, UK. [email protected] Source: O'Connor, D B Archer, J Hair, W M Wu, F C Neuropsychologia. 2001; 39(13): 1385-94 0028-3932

•

Annexin 1 (lipocortin 1) mimics inhibitory effects of glucocorticoids on testosterone secretion and enhances effects of interleukin-1beta. Author(s): Faculty of Medicine, Department of Neuroendocrinology, Imperial College of Science Technology and Medicine, Hammersmith Hospital, London, UK. [email protected] Source: Cover, P O Baanah Jones, F John, C D Buckingham, J C Endocrine. 2002 June; 18(1): 33-9 0969-711X

•

Anti-androgenic and hair growth promoting activities of Lygodii spora (spore of Lygodium japonicum) I. Active constituents inhibiting testosterone 5alpha-reductase. Author(s): Faculty of Pharmaceutical Sciences, Kinki University, Higashiosaka, Osaka, Japan. [email protected] Source: Matsuda, H Yamazaki, M Naruo, S Asanuma, Y Kubo, M Biol-Pharm-Bull. 2002 May; 25(5): 622-6 0918-6158

•

Crystalline dihydrotestosterone implants in the lateral septum of male rats. A positive effect on LH and FSH. Author(s): Department of Clinical Biochemistry, S. Cecilio University Hospital, Granada, Spain. Source: Roca, G Torres, J M Ruiz, E Ortega, E Endocr-Res. 2001 Feb-May; 27(1-2): 35-40 0743-5800

Nutrition

111

•

Defining 'relative' androgen deficiency in aging men: how should testosterone be measured and what are the relationships between androgen levels and physical, sexual and emotional health? Author(s): Department of Medicine, University of Adelaide, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia. Source: Haren, M T Morley, J E Chapman, I M O'Loughlin, P D Wittert, G A Climacteric. 2002 March; 5(1): 15-25 1369-7137

•

Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men. Author(s): Department of Internal Medicine and Therapeutics, Clinica Medica IRCCS Policlinico S. Matteo, University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy. [email protected] Source: Fogari, R Preti, P Derosa, G Marasi, G Zoppi, A Rinaldi, A Mugellini, A Eur-JClin-Pharmacol. 2002 June; 58(3): 177-80 0031-6970

•

Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulinlike growth factor 1 responses to acute resistance exercise. Author(s): Department of Physical Education, Kyungpook National University, Taegu, 702-701, Korea. Source: Youl Kang, Ho Hwan Kim, Seung June Lee, Woen Byrne, Heidi K J-StrengthCond-Res. 2002 May; 16(2): 179-83 1064-8011

•

Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. Author(s): Center on Aging, University of Connecticut Health Center, Farmington 06030-5215, USA. [email protected] Source: Kenny, Anne M Bellantonio, Sandra Gruman, Cynthia A Acosta, Ruben D Prestwood, Karen M J-Gerontol-A-Biol-Sci-Med-Sci. 2002 May; 57(5): M321-5 1079-5006

•

Ex vivo bioadhesion and in vivo testosterone bioavailability study of different bioadhesive formulations based on starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures. Author(s): Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000, Gent, Belgium. Source: Ameye, D Voorspoels, J Foreman, P Tsai, J Richardson, P Geresh, S Remon, J P JControl-Release. 2002 February 19; 79(1-3): 173-82 0168-3659

•

Failure to maintain the suppressed level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. Author(s): Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi, Higashinari-ku, Japan. [email protected] Source: Kinouchi, T Maeda, O Ono, Y Meguro, N Kuroda, M Usami, M Int-J-Urol. 2002 June; 9(6): 359-61 0919-8172

•

Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men. Author(s): Laboratorio de Lipidos y Lipoproteinas, Departamento de Bioquimica Clinica, Facultad de Farmacia y Bioquimica. Universidad de Buenos Aires, Argentina. [email protected] Source: Berg, G Schreier, L Geloso, G Otero, P Nagelberg, A Levalle, O Horm-MetabRes. 2002 February; 34(2): 87-92 0018-5043

112 Testosterone

•

Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice. Author(s): Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada. Source: Ekue, A Boulanger, J F Morissette, M Di Paolo, T J-Neuroendocrinol. 2002 September; 14(9): 731-6 0953-8194

•

Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies. Author(s): Department of Obstetrics and Gynaecology, University College London Hospital, London, UK. Source: Chatterjee, R Kottaridis, P D McGarrigle, H H Linch, D C Bone-MarrowTransplant. 2002 April; 29(7): 607-10 0268-3369

•

On call. My wife and I are both 62 and healthy. She started taking Prempro during her menopause eight years ago but has now decided to stop the hormones. I began taking DHEA five years ago, but I switched to AndroGel when my doctor gave me a prescription last year. Should I stay on AndroGel, go back to DHEA, or stop hormones? Source: Simon, H B Harv-Mens-Health-Watch. 2003 January; 7(6): 8 1089-1102

•

Oral testosterone replacement in Korean patients with PADAM. Author(s): Department of Urology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. Source: Hong, J H Ahn, T Y Aging-Male. 2002 March; 5(1): 52-6 1368-5538

•

Steroid hormone (hydrocortisone, oestradiol and testosterone) uptake, storage or induced synthesis in tetrahymena. Author(s): Department of Genetics, Cell and Immunobiology, Semmelweis University of Medicine, Budapest, Hungary. Source: Csaba, G Poteczin, E Feher, T Kovacs, P Cell-Biol-Int. 1998 November; 22(11-12): 875-8 1065-6995

•

Testosterone acts as a coronary vasodilator by a calcium antagonistic action. Author(s): Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK. Source: English, K M Jones, R D Jones, T H Morice, A H Channer, K S J-EndocrinolInvest. 2002 May; 25(5): 455-8 0391-4097

•

Testosterone is a potential augmentor of antioxidant-induced apoptosis in human prostate cancer cells. Author(s): Department of Internal Medicine, ARUP Institute, University of Utah, Salt Lake City 84132, USA. Source: Gunawardena, K Murray, D K Meikle, A W Cancer-Detect-Prevolume 2002; 26(2): 105-13 0361-090X

•

Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. Author(s): St Bartholomew's Hospital, London, UK. [email protected] Source: Kong, A Edmonds, P Lancet-Infect-Dis. 2002 November; 2(11): 692-9 1473-3099

•

Thymic structural changes in relation to seasonal cycle and testosterone administration in wall lizard Hemidactylus flaviviridis (Ruppell). Author(s): Department of Zoology, University of Delhi, India. Source: Hareramadas, B Rai, U Indian-J-Exp-Biol. 2001 July; 39(7): 629-35 0019-5189

•

Vesicles in the subacrosomal space and partial diaphragms in the subacrosomal nuclear envelope of round spermatids of a rat injected intravenously with gold

Nutrition

113

labeled-testosterone-bovine serum albumin conjugate: vesicular trafficking from acrosome to nucleus. Author(s): Department of Anatomy, Aichi Medical University School of Medicine, Yazako, Japan. [email protected] Source: Nishimura, T Nakano, T Okajimas-Folia-Anat-Jpn. 2002 May; 79(1): 15-23 0030154X

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMD®Health: http://my.webmd.com/nutrition

114 Testosterone

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to testosterone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com

•

Minerals Boron Source: Healthnotes, Inc.; www.healthnotes.com Boron Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html

•

Food and Diet Soy Source: Healthnotes, Inc.; www.healthnotes.com

115

CHAPTER 3. ALTERNATIVE MEDICINE AND TESTOSTERONE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to testosterone. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to testosterone and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “testosterone” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to testosterone: •

5 alpha-reductase-catalyzed conversion of testosterone to dihydrotestosterone is increased in prostatic adenocarcinoma cells: suppression by 15-lipoxygenase metabolites of gamma-linolenic and eicosapentaenoic acids. Author(s): Pham H, Ziboh VA. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 November; 82(4-5): 393-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589947&dopt=Abstract

•

A brief history of testosterone. Author(s): Freeman ER, Bloom DA, McGuire EJ. Source: The Journal of Urology. 2001 February; 165(2): 371-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176375&dopt=Abstract

•

A case of femoral neck fracture in a patient with severe testosterone deficiency. Author(s): Ohishi T, Koide Y, Takahashi M, Oikawa M, Kushida K.

116 Testosterone

Source: Journal of Bone and Mineral Metabolism. 1999; 17(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084402&dopt=Abstract •

A zinc based self setting ceramic bone substitute for local delivery of testosterone. Author(s): Gordon E, Lasserre A, Stull P, Bajpai PK, England B. Source: Biomed Sci Instrum. 1997; 33: 131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9731348&dopt=Abstract

•

Acquisition of chemoresistant phenotype by overexpression of the antiapoptotic gene testosterone-repressed prostate message-2 in prostate cancer xenograft models. Author(s): Miyake H, Nelson C, Rennie PS, Gleave ME. Source: Cancer Research. 2000 May 1; 60(9): 2547-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10811138&dopt=Abstract

•

Alterations of prostate biomarker expression and testosterone utilization in human LNCaP prostatic carcinoma cells by garlic-derived S-allylmercaptocysteine. Author(s): Pinto JT, Qiao C, Xing J, Suffoletto BP, Schubert KB, Rivlin RS, Huryk RF, Bacich DJ, Heston WD. Source: The Prostate. 2000 December 1; 45(4): 304-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11102955&dopt=Abstract

•

Beta-hydroxy beta-methylbutyrate (HMB) supplementation does not influence the urinary testosterone: epitestosterone ratio in healthy males. Author(s): Slater GJ, Logan PA, Boston T, Gore CJ, Stenhouse A, Hahn AG. Source: J Sci Med Sport. 2000 March; 3(1): 79-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839231&dopt=Abstract

•

Brain aromatase and 5alpha-reductase, regulatory behaviors and testosterone levels in adult rats on phytoestrogen diets. Author(s): Weber KS, Jacobson NA, Setchell KD, Lephart ED. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1999 June; 221(2): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10352124&dopt=Abstract

•

Changes in cerebral glucose metabolism and visuospatial capability in hypogonadal males under testosterone substitution therapy. Author(s): Zitzmann M, Weckesser M, Schober O, Nieschlag E. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109(5): 302-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11507655&dopt=Abstract

•

Daily profiles of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin, and of

Alternative Medicine 117

pituitary PRL mRNA and GH mRNA in male long evans rats in acute phase of adjuvant arthritis. Author(s): Roman O, Seres J, Herichova I, Zeman M, Jurcovicova J. Source: Chronobiology International. 2003 September; 20(5): 823-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535356&dopt=Abstract •

Decrease in the number of sperm associated with decreased blood testosterone levels in male rats treated with extracts from seven plants consumed by natives of northern Thailand. Author(s): Wanichacheewa S, Singtripop T, Sassa S, Sakamoto S, Mori T. Source: Environ. Toxicol. Pharmacol. 2001 June; 10(1-2): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382551&dopt=Abstract

•

Dehydroepiandrosterone (DHEA) and testosterone concentrations in human hair after chronic DHEA supplementation. Author(s): Kintz P, Cirimel V, Devaux M, Ludes B. Source: Clinical Chemistry. 2000 March; 46(3): 414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733296&dopt=Abstract

•

Delayed testosterone replacement restores nitric oxide synthase-containing nerve fibres and the erectile response in rat penis. Author(s): Baba K, Yajima M, Carrier S, Morgan DM, Nunes L, Lue TF, Iwamoto T. Source: Bju International. 2000 May; 85(7): 953-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10792181&dopt=Abstract

•

Developmental toxicity of testosterone in the crustacean Daphnia magna involves anti-ecdysteroidal activity. Author(s): Mu X, LeBlanc GA. Source: General and Comparative Endocrinology. 2002 November; 129(2): 127-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441123&dopt=Abstract

•

Diet and the duration of testosterone-dependent prostate cancer in Lobund-Wistar rats. Author(s): Pollard M, Wolter W, Sun L. Source: Cancer Letters. 2001 November 28; 173(2): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597786&dopt=Abstract

•

Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats. Author(s): Weber KS, Setchell KD, Stocco DM, Lephart ED.

118 Testosterone

Source: The Journal of Endocrinology. 2001 September; 170(3): 591-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524239&dopt=Abstract •

Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men. Author(s): Gardner-Thorpe D, O'Hagen C, Young I, Lewis SJ. Source: European Journal of Clinical Nutrition. 2003 January; 57(1): 100-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548304&dopt=Abstract

•

Effect of dietary administration of genistein, nonylphenol or ethinyl estradiol on hepatic testosterone metabolism, cytochrome P-450 enzymes, and estrogen receptor alpha expression. Author(s): Laurenzana EM, Weis CC, Bryant CW, Newbold R, Delclos KB. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2002 January; 40(1): 53-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731036&dopt=Abstract

•

Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease. Author(s): Thompson PD, Ahlberg AW, Moyna NM, Duncan B, Ferraro-Borgida M, White CM, McGill CC, Heller GV. Source: American Heart Journal. 2002 February; 143(2): 249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835027&dopt=Abstract

•

Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Author(s): Gonzales GF, Cordova A, Vega K, Chung A, Villena A, Gonez C, Castillo S. Source: Andrologia. 2002 December; 34(6): 367-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472620&dopt=Abstract

•

Effect of testosterone on the apneic threshold in women during NREM sleep. Author(s): Zhou XS, Rowley JA, Demirovic F, Diamond MP, Badr MS. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 January; 94(1): 101-7. Epub 2002 September 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391093&dopt=Abstract

•

Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in the rat corpus cavernosum and dorsal nerve. Author(s): Baba K, Yajima M, Carrier S, Akkus E, Reman J, Nunes L, Lue TF, Iwamoto T. Source: Urology. 2000 September 1; 56(3): 533-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962339&dopt=Abstract


•

Effects of anabolic precursors on serum testosterone concentrations and adaptations to resistance training in young men. Author(s): Brown GA, Vukovich MD, Reifenrath TA, Uhl NL, Parsons KA, Sharp RL, King DS. Source: International Journal of Sport Nutrition and Exercise Metabolism. 2000 September; 10(3): 340-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997957&dopt=Abstract

•

Effects of ChunDoSunBup Qi-training on growth hormone, insulin-like growth factor-I, and testosterone in young and elderly subjects. Author(s): Lee MS, Kang CW, Ryu H, Kim JD, Chung HT. Source: The American Journal of Chinese Medicine. 1999; 27(2): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467451&dopt=Abstract

•

Effects of Cordyceps sinensis on testosterone production in normal mouse Leydig cells. Author(s): Huang BM, Hsu CC, Tsai SJ, Sheu CC, Leu SF. Source: Life Sciences. 2001 October 19; 69(22): 2593-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712663&dopt=Abstract

•

Effects of Eurycoma longifolia jack on laevator ani muscle in both uncastrated and testosterone-stimulated castrated intact male rats. Author(s): Ang HH, Cheang HS. Source: Arch Pharm Res. 2001 October; 24(5): 437-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693547&dopt=Abstract

•

Effects of evodiamine on the secretion of testosterone in rat testicular interstitial cells. Author(s): Lin H, Tsai SC, Chen JJ, Chiao YC, Wang SW, Wang GJ, Chen CF, Wang PS. Source: Metabolism: Clinical and Experimental. 1999 December; 48(12): 1532-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599984&dopt=Abstract

•

Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulinlike growth factor 1 responses to acute resistance exercise. Author(s): Youl Kang H, Hwan Kim S, Jun Lee W, Byrne HK. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2002 May; 16(2): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991768&dopt=Abstract

•

Effects of Lepidium meyenii Walp and Jatropha macrantha on blood levels of estradiol-17 beta, progesterone, testosterone and the rate of embryo implantation in mice. Author(s): Oshima M, Gu Y, Tsukada S.

120 Testosterone

Source: The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science. 2003 October; 65(10): 1145-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600359&dopt=Abstract •

Ethyl acetate extraction procedure and isocratic high-performance liquid chromatographic assay for testosterone metabolites in cell microsomes. Author(s): Baltes MR, Dubois JG, Hanocq M. Source: J Chromatogr B Biomed Sci Appl. 1998 March 20; 706(2): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9551806&dopt=Abstract

•

Evaluation of a Tier I screening battery for detecting endocrine-active compounds (EACs) using the positive controls testosterone, coumestrol, progesterone, and RU486. Author(s): O'Connor JC, Davis LG, Frame SR, Cook JC. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2000 April; 54(2): 338-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774816&dopt=Abstract

•

Garlic supplementation increases testicular testosterone and decreases plasma corticosterone in rats fed a high protein diet. Author(s): Oi Y, Imafuku M, Shishido C, Kominato Y, Nishimura S, Iwai K. Source: The Journal of Nutrition. 2001 August; 131(8): 2150-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481410&dopt=Abstract

•

Gene expression profiling of testosterone and estradiol-17 beta-induced prostatic dysplasia in Noble rats and response to the antiestrogen ICI 182,780. Author(s): Thompson CJ, Tam NN, Joyce JM, Leav I, Ho SM. Source: Endocrinology. 2002 June; 143(6): 2093-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021174&dopt=Abstract

•

Genistein administration decreases serum corticosterone and testosterone levels in rats. Author(s): Ohno S, Nakajima Y, Inoue K, Nakazawa H, Nakajin S. Source: Life Sciences. 2003 December 26; 74(6): 733-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14654166&dopt=Abstract

•

Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: the effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone. Author(s): Maenpaa J, Hall SD, Ring BJ, Strom SC, Wrighton SA. Source: Pharmacogenetics. 1998 April; 8(2): 137-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10022752&dopt=Abstract


•

Immunocytochemical localization of bovine serum albumin (BSA) in the liver and testis of rats injected with testosterone-BSA, hydrocortisone-BSA or corticosteroneBSA. Author(s): Nishimura T, Nakano T. Source: Cell Structure and Function. 2000 June; 25(3): 161-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984099&dopt=Abstract

•

In vivo and in vitro stimulatory effects of Cordyceps sinensis on testosterone production in mouse Leydig cells. Author(s): Hsu CC, Huang YL, Tsai SJ, Sheu CC, Huang BM. Source: Life Sciences. 2003 September 5; 73(16): 2127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899935&dopt=Abstract

•

Infant feeding with soy formula milk: effects on the testis and on blood testosterone levels in marmoset monkeys during the period of neonatal testicular activity. Author(s): Sharpe RM, Martin B, Morris K, Greig I, McKinnell C, McNeilly AS, Walker M. Source: Human Reproduction (Oxford, England). 2002 July; 17(7): 1692-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093826&dopt=Abstract

•

Influence of testosterone on some behavioral reactions of male immature rats exposed to continual light. Author(s): Lambadjieva ND. Source: Methods Find Exp Clin Pharmacol. 1999 January-February; 21(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10222442&dopt=Abstract

•

Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline. Author(s): Barbenel DM, Yusufi B, O'Shea D, Bench CJ. Source: Journal of Psychopharmacology (Oxford, England). 2000 March; 14(1): 84-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10757260&dopt=Abstract

•

Microencapsulation of Leydig cells: a system for testosterone supplementation. Author(s): Machluf M, Orsola A, Boorjian S, Kershen R, Atala A. Source: Endocrinology. 2003 November; 144(11): 4975-9. Epub 2003 July 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960073&dopt=Abstract

•

Nuclear concentration of gold labeled-testosterone-bovine serum albumin conjugate injected intravenously in the hormone-target cells of rat. Author(s): Nishimura T, Ichihara I. Source: Cell Structure and Function. 1997 August; 22(4): 433-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9368717&dopt=Abstract

122 Testosterone

•

Nuclear translocation of gold labeled-testosterone-bovine serum albumin conjugate through the nuclear double membranes in rat spermatids. Author(s): Nishimura T, Nakano T. Source: Cell Structure and Function. 1997 December; 22(6): 621-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9591054&dopt=Abstract

•

Production of testosterone from phytosterol using a single-step microbial transformation by a mutant of Mycobacterium sp. Author(s): Lo CK, Pan CP, Liu WH. Source: Journal of Industrial Microbiology & Biotechnology. 2002 May; 28(5): 280-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986932&dopt=Abstract

•

Prostate cancer chemoprevention by green tea: in vitro and in vivo inhibition of testosterone-mediated induction of ornithine decarboxylase. Author(s): Gupta S, Ahmad N, Mohan RR, Husain MM, Mukhtar H. Source: Cancer Research. 1999 May 1; 59(9): 2115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10232597&dopt=Abstract

•

Protective role of isoflavones against the toxic effect of cypermethrin on semen quality and testosterone levels of rabbits. Author(s): Yousef MI, El-Demerdash FM, Al-Salhen KS. Source: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes. 2003 July; 38(4): 463-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856928&dopt=Abstract

•

Reduction of serum testosterone in men by licorice. Author(s): Armanini D, Bonanni G, Palermo M. Source: The New England Journal of Medicine. 1999 October 7; 341(15): 1158. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515764&dopt=Abstract

•

Requirement of c-jun for testosterone-induced sensitization to N-(4hydroxyphenyl)retinamide-induced apoptosis. Author(s): Shimada K, Nakamura M, Ishida E, Kishi M, Konishi N. Source: Molecular Carcinogenesis. 2003 March; 36(3): 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619033&dopt=Abstract

•

Restoration of spermatogenesis and fertility in azoospermic mutant mice by suppression and reelevation of testosterone followed by intracytoplasmic sperm injection. Author(s): Tohda A, Okuno T, Matsumiya K, Okabe M, Kishikawa H, Dohmae K, Okuyama A, Nishimune Y.


Source: Biology of Reproduction. 2002 January; 66(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751268&dopt=Abstract •

Serum luteinizing hormone, testosterone, and thyroxine and growth responses of ram lambs fed locoweed (Oxytropis sericea) and treated with vitamin E/selenium. Author(s): Richards JB, Hallford DM, Duff GC. Source: Theriogenology. 1999 October 15; 52(6): 1055-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735112&dopt=Abstract

•

Short-term leptin infusion does not affect circulating levels of LH, testosterone or cortisol in food-restricted pubertal male rhesus macaques. Author(s): Lado-Abeal J, Lukyanenko YO, Swamy S, Hermida RC, Hutson JC, Norman RL. Source: Clinical Endocrinology. 1999 July; 51(1): 41-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468964&dopt=Abstract

•

Stimulatory effects of selected PAHs on testosterone production in goldfish and rainbow trout and possible mechanisms of action. Author(s): Evanson M, Van Der Kraak GJ. Source: Comparative Biochemistry and Physiology. Toxicology & Pharmacology : Cbp. 2001 October; 130(2): 249-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574294&dopt=Abstract

•

Testosterone 5alpha-reductase inhibitor bisnaphthoquinone derivative from Impatiens balsamina. Author(s): Ishiguro K, Oku H, Kato T. Source: Phytotherapy Research : Ptr. 2000 February; 14(1): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641051&dopt=Abstract

•

Testosterone 5alpha-reductase inhibitory active constituents from Anemarrhenae Rhizoma. Author(s): Matsuda H, Sato N, Yamazaki M, Naruto S, Kubo M. Source: Biological & Pharmaceutical Bulletin. 2001 May; 24(5): 586-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11379787&dopt=Abstract

•

Testosterone treatment enhances regional brain perfusion in hypogonadal men. Author(s): Azad N, Pitale S, Barnes WE, Friedman N. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3064-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843144&dopt=Abstract

•

The effect of intraperitoneal melatonin supplementation on the release of thyroid hormones and testosterone in rats with hyperthyroid. Author(s): Mogulkoc R, Baltaci AK.

124 Testosterone

Source: Neuroendocrinol Lett. 2003 October; 24(5): 345-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14647010&dopt=Abstract •

The effects of feeding an Asian or Western diet on sperm numbers, sperm quality and serum hormone levels in cynomolgus monkeys (Macaca fascicularis) injected with testosterone enanthate (TE) plus depot medroxyprogesterone acetate (DMPA). Author(s): Suhana N, Sutyarso, Moeloek N, Soeradi O, Sri Sukmaniah S, Supriatna J. Source: International Journal of Andrology. 1999 April; 22(2): 102-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194642&dopt=Abstract

•

Torilin from Torilis japonica, as a new inhibitor of testosterone 5 alpha-reductase. Author(s): Park WS, Son ED, Nam GW, Kim SH, Noh MS, Lee BG, Jang IS, Kim SE, Lee JJ, Lee CH. Source: Planta Medica. 2003 May; 69(5): 459-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802730&dopt=Abstract

•

Use of antisense oligonucleotides targeting the antiapoptotic gene, clusterin/testosterone-repressed prostate message 2, to enhance androgen sensitivity and chemosensitivity in prostate cancer. Author(s): Gleave ME, Miyake H, Zellweger T, Chi K, July L, Nelson C, Rennie P. Source: Urology. 2001 August; 58(2 Suppl 1): 39-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502446&dopt=Abstract

•

Vesicles in the subacrosomal space and partial diaphragms in the subacrosomal nuclear envelope of round spermatids of a rat injected intravenously with gold labeled-testosterone-bovine serum albumin conjugate: vesicular trafficking from acrosome to nucleus. Author(s): Nishimura T, Nakano T. Source: Okajimas Folia Anat Jpn. 2002 May; 79(1): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199534&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

•


•

Chinese Medicine: http://www.newcenturynutrition.com/

•

drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

•

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

•

Google: http://directory.google.com/Top/Health/Alternative/


•

Healthnotes: http://www.healthnotes.com/

•

MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

•

Open Directory Project: http://dmoz.org/Health/Alternative/

•

HealthGate: http://www.tnp.com/

•

WebMD®Health: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to testosterone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Benign Prostatic Hyperplasia Source: Healthnotes, Inc.; www.healthnotes.com Benign Prostatic Hyperplasia Source: Integrative Medicine Communications; www.drkoop.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Canker Sores Source: Prima Communications, Inc.www.personalhealthzone.com Erectile Dysfunction Source: Healthnotes, Inc.; www.healthnotes.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Impotence Source: Prima Communications, Inc.www.personalhealthzone.com Male Infertility Source: Prima Communications, Inc.www.personalhealthzone.com

126 Testosterone

Menopause Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com Prostate Enlargement Source: Integrative Medicine Communications; www.drkoop.com Sexual Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Ulcers Source: Prima Communications, Inc.www.personalhealthzone.com Viral Hepatitis Source: Prima Communications, Inc.www.personalhealthzone.com •

Herbs and Supplements 7-keto Source: Healthnotes, Inc.; www.healthnotes.com Androstenedione Source: Healthnotes, Inc.; www.healthnotes.com Androstenedione Source: Prima Communications, Inc.www.personalhealthzone.com Aristolochia Alternative names: Snakeroot, Guaco; Aristolochia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com


Beta-carotene Source: Healthnotes, Inc.; www.healthnotes.com Boswellia Alternative names: Frankincense; Boswellia serrata Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Dehydroepiandrosterone Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com DHEA (dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Estrogen Source: Prima Communications, Inc.www.personalhealthzone.com Estrogens (combined) Source: Healthnotes, Inc.; www.healthnotes.com Gamma Oryzanol Source: Healthnotes, Inc.; www.healthnotes.com Gamma-Oryzanol Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10028,00.html Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Source: Prima Communications, Inc.www.personalhealthzone.com Methyltestosterone Source: Healthnotes, Inc.; www.healthnotes.com

128 Testosterone

Nettle Alternative names: Urtica dioica Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pregnenolone Source: Healthnotes, Inc.; www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Pygeum Alternative names: African Prune; Pygeum africanum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pygeum Alternative names: Prunus africanum, Pygeum africanum Source: Healthnotes, Inc.; www.healthnotes.com Sabal Serrulata Source: Integrative Medicine Communications; www.drkoop.com Sarsaparilla Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Saw Palmetto Alternative names: Serenoa serrulata, Serenoa repens, Sabal serrulata Source: Healthnotes, Inc.; www.healthnotes.com Saw Palmetto Alternative names: Serenoa repens, Sabal serrulata Source: Integrative Medicine Communications; www.drkoop.com Saw Palmetto Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,819,00.html Serenoa Repens Source: Integrative Medicine Communications; www.drkoop.com Siberian Ginseng Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com


Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,821,00.html Stanozolol Source: Healthnotes, Inc.; www.healthnotes.com Swertia Alternative names: Swertia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tribulus Puncture Alternative names: Puncture Vine, Goathead; Tribulus terrestris L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

131

CHAPTER 4. DISSERTATIONS ON TESTOSTERONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to testosterone. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “testosterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on testosterone, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Testosterone ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to testosterone. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Appetitive and Consummatory Sexual Behaviors in the Male Rat Following Castration and Testosterone Replacement: the Role of the Ventral Tegmental Area by Centeno, Soraya; PhD from Concordia University (Canada), 2002, 232 pages http://wwwlib.umi.com/dissertations/fullcit/NQ68202

•

Effect of Heavy-resistance Weight Lifting on Serum Levels of Testosterone and Androstenedione in Adult Men and Women. by Weiss, Lawrence Wayne, EDD from University of Georgia, 1979, 111 pages http://wwwlib.umi.com/dissertations/fullcit/8001051

•

Effects of Chronic Endurance Exercise upon Blood Testosterone Levels and the Hypothalamic-pituitary - Gonadal Axis in Trained Males by Hackney, Anthony C., PhD from Kent State University, 1986, 164 pages http://wwwlib.umi.com/dissertations/fullcit/8705799

132 Testosterone

•

Factors Affecting Plasma Levels of Dehydroepiandrosterone Sulfate and Testosterone in Male Pigs by Tan, Hock Seng; PhD from University of Guelph (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK39009

•

Hyperactivity and Testosterone Level in Prepubertal Boys: Is There a Relationship? by Chism, Muriel Morgan, EDD from University of Arkansas, 1984, 93 pages http://wwwlib.umi.com/dissertations/fullcit/8528881

•

Menstrual Profile of Salivary Testosterone and Its Implications for Changes in Coital Frequency across the Menstrual Cycle by Campbell, Benjamin Charles, PhD from Harvard University, 1990, 227 pages http://wwwlib.umi.com/dissertations/fullcit/9035450

•

Modulation of Alcohol Dehydrogenase and Ethanol Metabolism by Testosterone in the Spontaneously Hypertensive Rat by Rachamin, Gloria; PhD from University of Toronto (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK62228

•

Paternal Care Strategies in Two Related Species of Songbirds: the Roles of Testosterone and Prolactin by Van Roo, Brandi Lynn; PhD from Indiana University, 2002, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3054506

•

Prenatal Testosterone Exposure Alters Androgen Sensitivity of the Rat Prostate by Valle, Celeste Dawn; PhD from New York University, 2002, 143 pages http://wwwlib.umi.com/dissertations/fullcit/3048881

•

Role of Rna and Protein Synthesis in Rabbit Ovarian Follicular Testosterone Production by Losier, Arthur Joseph; PhD from McMaster University (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK42837

•

Salivary Hormonal Levels, Anxiety and Self-confidence Indices in Collegiate Football and Basketball Players over a Season of Play (college Athletes, Testosterone, Estradiol, Cortisol) by Bartolino, Amelie, PhD from The University of Texas at Austin, 1996, 244 pages http://wwwlib.umi.com/dissertations/fullcit/9633081

•

Studies on Testosterone and Ring D Hydroxylated Steroids in Human Pregnancy by Stern, Michael D; PhD from McGill University (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12052

•

Studies on Testosterone Metabolism in Rats: Effects of Estrogens by Lee, David Kai Hung; PhD from Queen's University at Kingston (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15019

•

Synergistic Effects of Testosterone and Estrogens on Male Sex Accessory Glands of Castrated Rats and Boars by Joshi, Harihar Sopandeo; AdvDeg from University of Guelph (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK09031

•

Testosterone As a Proximate Determinant of Somatic Energy Allocation in Human Males: Evidence from Ache Men of Eastern Paraguay by Bribiescas, Richard Gutierrez, PhD from Harvard University, 1997, 301 pages http://wwwlib.umi.com/dissertations/fullcit/9733172

•

Testosterone Metabolism by Pig Liver in Vitro Studies on Steroid [delta]4-5betareductases and 17beta-hydroxysteroid Dehydrogenase by Nduaguba, John Chukwuemeka; AdvDeg from Queen's University at Kingston (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK05739

Dissertations 133

•

Testosterone Modulation of Plasma Gonadotropin and Prolactin Patterns by Grosser, Peter M; PhD from McGill University (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL46101

•

The Acute and Chronic Effects of Marathon Training on the Function of the Hypothalamic - Pituitary - Gonadal Axis of Male Runners (reproductive System, Testosterone, Gonadotropins) by MacConnie, Susan Ellisa, PhD from The University of Michigan, 1985, 98 pages http://wwwlib.umi.com/dissertations/fullcit/8520937

•

The Effects of Estrogen, Progesterone, and Testosterone on the Viability and Proliferation of A549 Lung Macrophages in Cell Culture by Hall, Deshannon; Ms from The University of Mississippi Medical Center, 2002, 97 pages http://wwwlib.umi.com/dissertations/fullcit/1408842

•

The Effects of Food Restriction and Testosterone Level on Reproductive Success in Wild House Mice, Mus Musculus by Kruper, Jill Hollingsworth; PhD from University of Louisville, 2002, 88 pages http://wwwlib.umi.com/dissertations/fullcit/3078070

•

The Effects of Growth and Exercise on Protein Turnover Sensitivity to Testosterone Administration in Skeletal Muscle of Prepubertal Rats by Malcolm, Susan Anne; PhD from Simon Fraser University (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65981

•

The Effects of Testosterone and Aromatase on Paternal Behavior and Aggression by Trainor, Brian Charles; PhD from The University of Wisconsin - Madison, 2003, 133 pages http://wwwlib.umi.com/dissertations/fullcit/3089575

•

The Relationship of Testosterone Concentration, Spatial Ability, and Sex Role Identification in Women Teaching Secondary Mathematics and Primary Grades by Ware, Dorothy Lee, EDD from University of Houston, 1982, 101 pages http://wwwlib.umi.com/dissertations/fullcit/8229085

•

The Secretory Patterns of Luteinizing Hormone and Testosterone in the Ram As Influenced by Sexual Activity, Season, Age and Breed by Sanford, Lee Merritt; PhD from The University of Manitoba (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK21453

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

135

CHAPTER 5. CLINICAL TRIALS AND TESTOSTERONE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning testosterone.

Recent Trials on Testosterone The following is a list of recent trials dedicated to testosterone.8 Further information on a trial is available at the Web site indicated. •

Effect Of Dutasteride On Intraprostatic Dihydrotestosterone (DHT) Levels Condition(s): Benign Prostatic Hyperplasia Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: This study is being done to determine how much certain hormone levels in the prostate decrease when a patient takes dutasteride. Male patients at least 50 years old will take either dutasteride or a placebo (dummy pill) once daily by mouth for 3 months prior to having a surgery to reduce the size of their prostate. During the surgery, very small pieces of the prostate that are removed will be tested to see how much dihydrotestosterone and testosterone (male hormones) are in the tissue. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062790

•

Phase II Randomized Study of Physiologic Premenopausal, HIV-Positive Women

Testosterone

Condition(s): HIV Infections; Cachexia Study Status: This study is currently recruiting patients. 8 These

are listed at www.ClinicalTrials.gov.

Replacement

in

136 Testosterone

Sponsor(s): FDA Office of Orphan Products Development; Charles R. Drew University of Medicine and Science Purpose - Excerpt: Objectives: I. Determine whether physiologic testosterone replacement can increase fat-free mass, therefore contributing to weight maintenance, improved muscle function, and quality of life in HIV-infected women. II. Examine the mechanism of testosterone-induced increase in fat-free mass. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004400 •

Physiologic Effects of PRMS & Testosterone in the Debilitated Elderly Condition(s): Muscle Weakness; Muscular Atrophy Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study's primary objective is to determine the independent and combined effects of progressive resistance muscle strength training and testosterone on the development of sustainable improvements in physical function. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018356

•

Randomized Study of Testosterone and Progressive Resistance Exercise in Men With Burn Injury Condition(s): Burns Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); University of Texas Purpose - Excerpt: Objectives: I. Determine whether testosterone normalization ameliorates muscle protein hypercatabolism by increasing net protein synthesis in men with burn injury. II. Determine whether the effectiveness of testosterone is enhanced by stimulation of inward amino acid transport as a consequence of hyperaminoacidemia in these men. III. Determine whether testosterone normalization during hospitalization minimizes the need for rehabilitation by increasing net protein synthesis and preserving skeletal muscle in these men. IV. Determine whether testosterone normalization after hospital discharge and throughout convalescence increases muscle strength and lean body mass after burn injury by increasing net protein synthesis. V. Determine whether testosterone combined with progressive resistance exercise during convalescence confers added benefits on muscle protein synthesis, and in turn, lean body mass and muscle strength in these patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006129

Clinical Trials 137

•

Rapid Hormone Cycling With Testosterone and Leuprolide Combined With Docetaxel in Treating Patients With Recurrent or Metastatic Adenocarcinoma (Cancer) of the Prostate Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide may fight prostate cancer by reducing the production of testosterone. Some tumors become resistant to hormone therapy. Alternating short schedules of testosterone and leuprolide combined with a chemotherapy drug, such as docetaxel, may reduce resistance to the hormone therapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of rapid hormone cycling using testosterone and leuprolide combined with docetaxel in treating patients who have recurrent or metastatic adenocarcinoma of the prostate (prostate cancer). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070369

•

Testosterone for HIV-Positive Men with Reduced Serum Testosterone Levels and Abdominal Fat Condition(s): HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if treatment with testosterone will reduce abdominal fat in HIV-positive men. Many HIV patients on antiretroviral therapy show an increase in abdominal fat. Studies have shown that treatment with testosterone may decrease abdominal fat. This study will determine if testosterone will reduce abdominal fat in HIV patients. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009555

•

Testosterone in Treating Patients With Progressive Prostate Cancer That No Longer Responds to Hormone Therapy Condition(s): stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: High doses of testosterone may be effective in killing prostate cancer cells that no longer respond to hormone therapy. PURPOSE: Phase I trial

138 Testosterone

to study the effectiveness of testosterone in treating patients who have progressive prostate cancer that no longer responds to hormone therapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006044 •

The Effect of 5-alpha Reductase on Testosterone in Men Condition(s): Sex Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The enzyme 5-alpha reductase is present in small amounts in muscle and converts testosterone to dihydrotestosterone (DHT). Testosterone affects lean body tissue, muscle size, muscle strength, and sexual function in men. This study will evaluate how 5-alpha reductase influences the effects of testosterone in young healthy men. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070733

•

The Effect of Testosterone Supplementation on Rehabilitation Outcomes Condition(s): Aging; Frail Elderly; Rehabilitation Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Rehabilitation Research and Development Service Purpose - Excerpt: The objective of this project is to determine the safety and efficacy of testosterone supplementation as an adjunct to traditional rehabilitation therapy in the care of deconditioned older men. Our long range goal is to determine whether other hormones (e.g., combined testosterone and growth hormone) are helpful as an adjunct to traditional rehabilitation therapy. This project is important to the VA health care system because 38% of American veterans are aged (age > 65 years), bioavailable testosterone is diminished in older age men, low testosterone is associated with impaired muscle strength, and lack of muscle strength hinders rehabilitation. Older men who are not successfully rehabilitated often get admitted to nursing homes for long term care, at a cost of approximately $40,000/year. Payment for long term care is currently one of our most difficult health care problems. If testosterone supplementation improves rehabilitation outcomes, as our pilot data suggest it will, patients will be more satisfied and long-term care financial resources will be saved. We will conduct a randomized, placebo-controlled trial to test the hypothesis that supplementation with testosterone improves rehabilitation outcomes in deconditioned older men. Specifically, we will screen all hospitalized older men with delayed discharge from the hospital (> 7 day hospital stay). Men who have at least one new impairment in their ability to perform activities of daily living (e.g., inability to walk), low serum testosterone concentration, and no contraindications (e.g., prostate or breast cancer) will be offered the opportunity

Clinical Trials 139

to participate. Study participants will be randomized to receive either testosterone (5 mg transdermally each night) or placebo (matching transdermal patch) daily in a doubleblind fashion for the duration of their hospital course (expected average duration of study is 29 days). Subjects will then receive their rehabilitation as usual, with all members of the health care team blinded as to whether the subject is receiving testosterone or placebo. At baseline, weekly, at discharge, and at 6 and 12 months after discharge, subjects will be assessed using validated measures (i.e., Functional Independence Measure - FIM). Our hypothesis is that testosterone supplementation, as an adjunct to traditional rehabilitation therapy, will improve rehabilitation outcomes. Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): Thomas Mulligan 804-675-5181 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00037999 •

AIDS Wasting in Women: Anabolic Effects of Testosterone Condition(s): AIDS Wasting Syndrome Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The study is a 6 month, placebo-controlled study of transdermal testosterone for women with HIV-associated weight loss. Women with AIDS wasting have been found to have low testosterone levels. This study is designed to test the efficacy of physiologic testosterone dosing to improve weight, muscle mass and quality of life indices, including energy level, appetite and libido, in androgen deficient women with AIDS wasting. After 6 months, all women receive open label transdermal testosterone for an additional 6 months. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006158

•

A Study of Megestrol Acetate Alone or in Combination with Testosterone Enanthate Drug in the Treatment of HIV-Associated Weight Loss Condition(s): HIV Infections; HIV Wasting Syndrome Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: To test the hypothesis that the predominant accrual of fat rather than lean body mass (LBM) that occurs during treatment of HIV-associated wasting with megestrol acetate may be improved by treatment with megestrol acetate and testosterone enanthate in combination. Body wasting is an increasingly frequent AIDSdefining condition in individuals infected with HIV. Increasing caloric intake fails to consistently restore lean tissue patients with HIV associated weight loss. Megestrol acetate has been shown to stimulate appetite and weight gain in subjects with cancer and in those with HIV associated weight loss. However, the weight gained during treatment with megestrol acetate was predominantly or exclusively fat. An important factor is the preferential increase in body fat seen in both of these studies may have been

140 Testosterone

due to hypogonadism that occurs as a result of treatment with megestrol acetate, a progestational agent. Hypogonadism is associated with an increase in body fat and a decrease in LBM. Concomitant testosterone replacement should substantially increase the amount of LBM accrued during megestrol acetate therapy. This study will determine whether anabolic potential can be realized when caloric intake is increased in the absence of concomitant hypogonadism. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001079 •

Effects on the Brain of Lupron Induced Hypogonadotropic Hypogonadism with and without Testosterone Replacement Condition(s): Hypogonadism Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: There is evidence that suggests male sex hormones (androgens) play a significant role in brain (central nervous system) functioning. In studies conducted with animals, researchers have documented that male sex hormones (androgens) are associated with neurotransmitter (serotonin) function, sexual behavior, aggression, and other non-reproductive behavior. Similar findings have been seen in studies involving humans. Androgens are thought to be involved in some neurologic conditions. Tourette's syndrome which is seen more often in males than females has caused researchers to look more closely at the effects of androgens on the brain. This study is designed to examine the effects of testosterone on brain (CNS) activity by first stopping testosterone release and then replacing it. Researchers will evaluate mood, behavior, cognitive (mental) function, physiologic response to serotonergic agonists and regional cerebral blood flow (r-CBF). This study will attempt to answer the following questions; 1. Is a person's mental functioning a result of being male or female (gender) or a result of the hormonal condition 3. Does the decrease of blood flow (r-CBF) to specific areas of the brain (prefrontal cortex) in women whose ovaries are not releasing hormones (hypogonadal state) also occur in men 4. Will the mental rotation task better identify hormone (gonadal steroid) differences in r-CBF 5. Do hormones directly influence the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis 6. Does the hormonal state of a patient directly affect levels of chemicals and steroids in the cerebrospinal fluid (CSF). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001412

•

Phase II Study of Leuprolide and Testosterone for Men with Kennedy's Disease or Other Motor Neuron Disease Condition(s): Spinal Muscular Atrophy; Amyotrophic Lateral Sclerosis; Spinobulbar Muscular Atrophy Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Ohio State University

Clinical Trials 141

Purpose - Excerpt: Objectives: I. Evaluate the effects of androgen suppression with leuprolide and androgen replacement with testosterone enanthate on muscle strength in men with Kennedy's disease or other motor neuron disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004771 •

Study of Estradiol and Testosterone Levels and Breast Cancer Risk in Postmenopausal Women Previously Enrolled on the Breast Cancer Prevention Trial Condition(s): Breast Cancer Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Surgical Adjuvant Breast and Bowel Project (NSABP); National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Determining how hormones, such as estradiol and testosterone, may increase the risk of developing breast cancer may help doctors identify postmenopausal women who are at risk. PURPOSE: Clinical trial to study estradiol and testosterone levels and the risk of developing breast cancer in postmenopausal women. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074113

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “testosterone” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

142 Testosterone

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

•

For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

•

For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

•

For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

143

CHAPTER 6. PATENTS ON TESTOSTERONE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “testosterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on testosterone, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Testosterone By performing a patent search focusing on testosterone, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

144 Testosterone

example of the type of information that you can expect to obtain from a patent search on testosterone: •

17-azolyl steroids useful as androgen synthesis inhibitors Inventor(s): Brodie; Angela (Fulton, MD), Njar; Vincent C. O. (Baltimore, MD) Assignee(s): The University of Maryland, Baltimore (Baltimore, MD) Patent Number: 5,994,335 Date filed: October 17, 1997 Abstract: Androgen synthesis inhibitors, as well as methods for the use of the same to reduce plasma levels of testosterone and/or dyhydrotestosterone, and to treat prostate cancer and benign prostatic hypertrophy, are disclosed. Excerpt(s): The present invention relates to novel 17-azolyl steroids which are useful as androgen synthesis inhibitors, as well as methods for the use of the same to reduce plasma levels of testosterone and/or dyhydrotestosterone, and to treat prostate cancer and benign prostatic hypertrophy. Breast cancer kills 45,000 women per year. In addition, prostate cancer now ranks as the most prevalent cancer in men. Approximately 160,000 new cases are diagnosed with prostate cancer each year. Of these, 35,000 will die of metastatic disease. It has been proposed that selective aromatase (estrogen synthetase) inhibitors to control estrogen production would be useful agents for treatment of breast cancer in women (Bolla et al, N. Eng. J. Med., 337:295-300 (1997)). In addition, in men, aromatase inhibitors may be useful for conditions associated with estrogen excess, such as gynecomastia and oligospermia (Coen et al, New Eng. J. Med., 324:317-322 (1991); and Hsiang et al, J. Steroid Biochem., 26:131-136 (1987)). It has also been suggested that aromatase inhibitors might be useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH) (Henderson, Annals Med., 23:201-203 (1991)). Web site: http://www.delphion.com/details?pn=US05994335__

•

Acute testosterone administration Inventor(s): Cole; Robert (2519 Alamo County Cir., Alamo, CA 94507), Rubsamen; Reid M. (Alamo, CA) Assignee(s): Aradigm Corporation (Hayward, CA), Cole; Robert (Hayward, CA) Patent Number: 6,428,769 Date filed: May 2, 2000 Abstract: The libido of adult human female patients is increased by the intrapulmonary delivery of testosterone. A formulation of testosterone is aerosolized and inhaled into a patient's lungs where particles of testosterone deposits on lung tissue and then enter the patient's circulatory system. The patient's testosterone level is enhanced well above baseline levels for a short period and subsides to baseline levels with normal metabolism thereby providing desired short term effects on enhanced libido without undesirable effects of long term enhanced testosterone levels. Additional formulations are provided including formulations for aerosolized delivery of sildenafil citrate which are delivered to male or female patients.

Patents 145

Excerpt(s): This invention relates generally to a method of treating women with a decreased libido. More specifically, the invention relates to acute non-invasive administration of testosterone to enhance libido over a discrete period of time. The presence of a normal amount of libido, defined as the urge to engage in sexual activity, is an important component of an individual's well-being. In both men and women the primary naturally occurring hormone responsible for libido is testosterone. In males, the baseline testosterone level is a relatively constant throughout life, decreasing slowly in old age. In contrast, women elaborate testosterone only as part of the process of ovulation. Each maturing follicle produces testosterone at the mid-point of the menstrual cycle, consistent with observations that female libido peaks with ovulation. As a woman ages, the number of maturing follicles per month decreases, and there is a decreasing total amount of testosterone produced. A common complaint of post menopausal women is decreased libido. This decrease in libido is characterized by a lack of interest in sexual intercourse, the lack of ability to achieve orgasm, or decrease in intensity of orgasm. It is important to note that this decrease in libido is often associated with a profound sense of loss of a once normal and active interest in sexual activity. Web site: http://www.delphion.com/details?pn=US06428769__ •

Anti-peptide antibody against human cytochrome P450 3A4 Inventor(s): Lu; Anthony Y. H. (Westfield, NJ), Wang; Regina W. (Montvale, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,300,476 Date filed: April 9, 1998 Abstract: Anti-peptide antibody raised against a portion of human cytochrome P450 3A4 is disclosed. A particular anti-peptide antibody was raised against a 21-amino acid peptide corresponding to residues 253-273 of human cytochrome P450 3A4. High titer antibodies were produced by rabbits immunized with this peptide as judged by ELISA. This anti-peptide antibody is specific for human CYP3A4 and exhibited greater than 9095% inhibition of testosterone 6.beta.-hydroxylation, while other cytochrome P450mediated reactions in human liver microsomes were not inhibited. An inhibitory epitope has been mapped within amino acids 261-267 of human CYP3A4. Excerpt(s): The present invention relates to an anti-peptide antibody raised against a portion of human cytochrome P450 3A4. A particular anti-peptide antibody was raised against a 21-amino acid peptide corresponding to residues 253-273 of human cytochrome P450 3A4, which is both specific to CYP3A4 and effectively inhibits CYP3A4 activity. The use of in vitro metabolism of therapeutic agents to address the potential in vivo induction, inhibition, drug-drug interaction and individual variability issues is known (for a recent review, see Rodrigues, 1994, Biochem. Pharmacol. 48: 2147-2156). Central to these studies is the unambiguous identification of specific drug-metabolizing enzyme(s), particularly human cytochrome P450 isoform(s) responsible for the metabolism of drugs. This objective can be achieved by using selective cytochrome P450 inhibitors, antibodies, recombinant cytochrome P450s and correlation analysis (Rodrigues, 1994, Biochem. Pharmacol. 48: 2147-2156). Polyclonal or monoclonal antibodies produced against purified cytochrome P450 or specific peptide sequences unique to individual cytochrome P450 isoforms have been used to study the regulation, structure and function of cytochrome P450s. Web site: http://www.delphion.com/details?pn=US06300476__

146 Testosterone

•

Combination therapy for androgenic alopecia with antisense oligonucleotides and minoxidil Inventor(s): Hoke, Jr.; Glenn D. (Mount Airy, MD) Assignee(s): Dyad Pharmaceutical Corporation () Patent Number: 5,994,319 Date filed: April 14, 1997 Abstract: Minoxidil has been shown to stimulate hair growth or inhibit the loss of hair in a number of patients beginning to develop androgenic alopecia. The mechanism by which minoxidil (2,4-pyrimidinediamine, 6-(1-piperidinyl)-3-oxide) alters the hair growth cycle is uncertain, but is thought to act by increasing vascular circulation to the hair follicle. Inhibitors of steroid metabolism, particularly those that inhibit the conversion of testosterone to dihydrotestosterone, have shown effects on hair cycles, including inhibition of hair loss. One class of enzymes targeted by these inhibitors are the steroid 5-alpha reductases. Minoxidil used in conjunction with effectors of steroid metabolism, leads to enhanced hair growth and decreased rates of hair loss. This specification relates to the use of antisense oligonucleotides targeting 5-alpha reductases used in conjunction with other hair growth enhancers and/or hair loss inhibitors. Excerpt(s): This invention relates to methods of reducing hair loss and promoting hair regrowth, and more particularly to methods using antisense oligonucleotides that effectively reduce the expression of 5-alpha reductase types 1 or 2 in conjunction with the use of (2,4-pyrimidinediamine, 6-(1-piperidinyl)-3-oxide) (commonly known as minoxidil) for the treatment of androgenic alopecia. As used herein, unless otherwise indicated, the term "antisense" or "antisense therapeutic" refers to oligonucleotides, modified oligonucleotides or other chemical compositions that bind in a sequence specific manner to a specified gene, its pre-mRNA, or its mRNA. As used herein, unless otherwise indicated, the term "oligonucleotide" includes both oligomers of ribonucleotides, i.e. oligoribonucleotides, and oligomers of deoxyribonucleotides, i.e., oligodeoxyribonucleotides or oligodeoxynucleotides. Web site: http://www.delphion.com/details?pn=US05994319__

•

Combined use of GnRH agonist and antagonist Inventor(s): Furuya; Shuichi (Tsukuba, JP), Suzuki; Nobuhiro (Tsukuba, JP) Assignee(s): Takeda Chemical Industries, Ltd. (Osaka, JP) Patent Number: 6,015,789 Date filed: August 14, 1997 Abstract: The present invention relates to a pharmaceutical luteinizing hormone releasing hormone agonist in combination with a luteinizing hormone releasing hormone antagonist. By using a luteinizing hormone releasing hormone agonist and a luteinizing hormone releasing hormone antagonist in combination, the transient exacerbation with elevation of serum testosterone and estrogen owing to the pituitarygonadotropic action (acute action) manifested immediately following an initial dose of the luteinizing hormone releasing hormone agonist can be successfully obviated. Excerpt(s): This application is a.sctn.371 application of PCT/JP97/01459, filed Apr. 25, 1997. The present invention relates to a pharmaceutical comprising a compound having luteinizing hormone releasing hormone activity in combination with a nonpeptide

Patents 147

compound having luteinizing hormone releasing hormone antagonizing activity. Superactive peptide analogs of luteinizing hormone releasing hormone (hereinafter referred to sometimes as LH-RH) which is one of the hormones originating from the hypothalamus [Schally, A. V. et al., J. Biological Chemistry, 246, 7230-7236, 1971 and Burgus, R. et al., Proc. Natl. Acad. Sci. USA, 69, 278-282, 1972] are superagonists or agonists of LH-RH receptors and, if administered repeatedly, suppress the production and release of luteinizing hormone releasing hormone in the hypophysis to weaken the responsiveness of the testes and ovaries to luteinizing hormone releasing hormone and consequently reduce the secretion of testosterone and estrogen. It is, therefore, known that these compounds exhibit antitumor activity in cancers dependent on such hormones, for example carcinoma of the prostate, and actually they have been put to use clinically. These compounds are also used broadly as therapeutic drugs for endometriosis, hystereoma, and precocious puberty. Web site: http://www.delphion.com/details?pn=US06015789__ •

Compositions and treatments for reducing potential unwanted side effects associated with long-term administration of androgenic testosterone precursors Inventor(s): Bucci; Luke R. (West Valley City, UT) Assignee(s): Weider Nutrition International, Inc (Salt Lake City, UT) Patent Number: 6,117,429 Date filed: August 11, 1998 Abstract: A method for reducing potential adverse effects of androgenic testosterone precursors by interfering with production or action of testosterone and estrogen metabolites by nutrient combinations is described. Although androgenic testosterone precursors themselves have little or no toxicity, there is the potential for their metabolites, estradiol and dihydrotestosterone, to enhance or cause hormone-responsive illnesses such as breast or prostatic cancer, benign prostatic hyperplasia, or hirsutism or acne in women. The use of the invented nutrient combinations reduces the formation or action of estradiol and dihydrotestosterone, thereby reducing potential adverse effects from increased production of these hormones following androgenic testosterone precursor administration. This may be accomplished without negating the effects of testosterone on muscle anabolism. The nutrient combinations include androstenedione, DHEA, pregnenolone, androstenediols, norandrostenedione and norandrostenediols, and natural products which reduce estrogen effects in the estrogen-responsive tissues, and substances to reduce formation of dihydrotestosterone from testosterone in prostate tissue. Excerpt(s): The invention relates to the use of nutrient combinations to prevent or reduce potential adverse effects from administration of androgenic testosterone precursors to humans and other mammals Specifically, the invention relates to coadministration of androgenic testosterone precursors such as pregnenolone, androstenediols, norandrostenediols, norandrostenedione, androstenedione or dehydroepiandrosterone in combination with natural products which inhibit estrogen effects in liver, adipose, prostate, ovarian, uterine, breast and other estrogen-responsive tissues, and substances which inhibit the production of dihydrotestosterone in prostate tissue. Androstenedione (.DELTA.sup.4 -androstene-3,17-dione) is an adrenal steroid hormone. Pregnenolone is a precursor for dehydroepiandrosterone. Dehydroepiandrosterone (DHEA) is a precursor of androstenedione. Androstenedione is a direct precursor of estrone and testosterone in target tissues that possess the

148 Testosterone

appropriate receptors and enzymes. Androstenediols are direct precursors for testosterone after oral administration in adult humans (unpublished data). 19Norandrostenedione is a precursor for 19-nortestosterone, which has anabolic actions similar to testosterone, with less androgenic actions. 19-Norandrostenedione is a potential precursor for estrone. Testosterone is important for the development and maintenance of male sexual organs and characteristics, behavioral effects, anabolic (growth-promoting) actions, and metabolic effects for all tissues, especially muscles, liver and kidney. (Kutsky, R. J., Handbook of Vitamins, Minerals and Hormones, 2.sup.nd ed., Van Nostrand Reinhold Company, New York, 1981). Estrogens are essential for the development and maintenance of female reproductive organs and characteristics, pregnancy, and metabolic effects for all tissues (Kutsky, 1981). Androstenedione levels in tissues, including skeletal muscle, of men and women decrease significantly with age. (Deslypere, J. P. and Vermeulen, A., Influence of age on steroid concentrations in skin and striated muscle in women and in cardiac muscle and lung tissue in men, J. Clin. Endocrinol. Metab. 61:648-653 (1985)). Since muscle wasting is associated with aging, these findings suggest that the loss of androstenedione is involved in muscle wasting. The corollary that androstenedione administration would maintain muscle mass is enticing, but has not been studied yet. Nevertheless, the data support an anabolic effect of androstenedione on muscle tissue in both men and women, with more effectiveness in men. Web site: http://www.delphion.com/details?pn=US06117429__ •

Compositions, methods and devices for the transdermal delivery of drugs Inventor(s): Christensen; Michael S. (215 Springhouse La., Merion, PA 19066), Portman; Edward Malcolm (659 Peachtree St., Suite 224, Atlanta, GA 30308), Schmirler; Dennis Lee (2112 Baypoint La., Hartland, WI 53029) Assignee(s): none reported Patent Number: 6,214,374 Date filed: May 22, 1996 Abstract: The present invention is directed to compositions, and methods for the delivery of drugs. Devices for the transdermal delivery of drugs are also provided. Specifically, the present invention relates to hydrogel compositions comprising water and a base mixture, in which the base mixture comprises: (i) a gelling agent consisting of methycellulose or at least one natural gum, or a mixture thereof; (ii) at least one natural gum: (iii) glucose; (iv) propylparaben; (v) methyl paraben; and (vi) sodium chloride.The compositions may further comprise pectin, glycolic, alcoholic or oil-based additives, a coloring, fragrance, or other pharmaceutically acceptable additive. The compositions may further comprise substituted ureas of the formula R--NH--CO--NH.sub.2 such as butylurea. The compositions may further comprise drugs such as hormones selected from progesterone, progestin, estrogen and testosterone. Methods for the treatment of disorders responsive to hormone therapy are also provided. Excerpt(s): The present invention relates to compositions for the transdermal delivery of hormones comprising a hydrogel-forming base mixture and a skin permeation enhancer. Methods for the treatment of disorders responsive to the administration of hormones are also provided. The present invention further relates to devices for the transdermal delivery of drugs. A recent trend in the pharmaceutical industry has been the development of new drug delivery systems for both old and new drugs. Much of the current research in drug delivery technology is aimed at developing formulations and

Patents 149

devices that improve the therapeutic effectiveness of drugs over conventional means of administration by controlling the rate, time and place of release of drugs in the body. Conventional dosage types include sublingual (under the tongue), oral (capsules, tablets, liquids), injectable, nasal and parenteral (suppository and non-oral) forms. While oral dosage forms comprise a substantial majority of all present dosage forms and offer ease of administration and low cost-per-use, they can suffer from inconvenient dosing intervals, side effects and reduced efficacy. Conventional dosage forms have disadvantages in certain patients, including unpredictable blood levels, difficult or uncomfortable administration and poor compliance. In order to maintain optimum blood levels, some conventional forms of drug delivery require frequent doses which can be difficult to remember or understand, particularly for the elderly patient. Failure to comply with a recommended drug regimen can endanger a patient's health. Web site: http://www.delphion.com/details?pn=US06214374__ •

Formulations for peptide release Inventor(s): Trigg; Timothy E. (Warrawee, AU), Walsh; John D. (Curl Curl, AU) Assignee(s): Peptech Limited (New South Wales, AU) Patent Number: 6,211,152 Date filed: February 17, 1999 Abstract: A pharmaceutical and/or veterinary formulation comprising deslorelin and an excipient, the formulation being characterised in that, in vitro, it releases deslorelin into phosphate buffered saline, as hereinbefore described, at 37.degree. C. at a rate of about 2-80.mu.g/day for at least 200 days. The formulation may be used for prevention of reproductive function, particularly in dogs and cats, and for the treatment, particularly in humans, of prostate and breast cancer and other diseases and conditions where suppression of testosterone or estradiol levels is beneficial. Excerpt(s): The present invention relates to pharmaceutical and veterinary formulations for the sustained release of deslorelin which is an agonist of the peptide gonadotropin releasing hormone (GnRH). Uses of the formulations include prevention of reproductive function, particularly in dogs and cats, and treatment, particularly in humans, of prostate and breast cancer and other diseases or conditions where suppression of testosterone or estradiol levels is beneficial. Uncontrolled reproduction in domestic pets is a world wide problem. In less developed countries, reproduction of domestic cats and dogs is relatively uncontrolled. Sporadic programs of work exist aimed at controlling reproduction in these animals by surgical castration. In the more developed countries, reproduction is controlled more by ovarectomy in females and in some cases, by orchidectomy in males, or by physically locking away animals to prevent mating. Surgical techniques, no matter how minor, carry some risk. Many pet owners are also loathe to have their animal surgically modified and will tolerate the problems of uncontrolled reproduction and associated behaviour. To remove the ability to reproduce from domestic pets without the use of surgery and without resorting to lengthy kennelling procedures has been an objective of the small animal research industry for some years. Drugs which are currently available for this process, are steroid-based drugs. They produce unpleasant side effects, particularly after lengthy use, and they are not widely used. Web site: http://www.delphion.com/details?pn=US06211152__

150 Testosterone

•

Genital vasodilator Inventor(s): Toppo; Shaina (3080 Yankee Clipper Dr., Las Vegas, NV 89117) Assignee(s): none reported Patent Number: 6,403,658 Date filed: September 21, 2000 Abstract: The goal in the treatment of female dysfunction is to increase blood flow to the genitals. Heretofore, treatments/developments have focused on prostaglandin E-I creams, topical sildenafil, aminoacids, etc, ingested systemic medications such as sildenafil, phentolamine, etc and mechanical devices. Our invention is a direct, local topical vasodilator with plant estrogen added to eliminate genital dryness, Nmethylnicotinate and DHEA which is precusor for, among others, the hormone testosterone. Testosterone is important in both male and female sexuality. Excerpt(s): Recent scientific publications (e.g. The Journal of the American Medical Associations) have reported that 43% of women experience some kind of sexual dysfunction. Some investigators have assigned four subclasses to the general term of female sexual dysfunction: 1) Sexual Arousal Disorder--whereby sexual thoughts occur, however, these thoughts are not communicated to the clitoris, 2) Orgasmic Disorder-inability to have orgasm, 3) Sexual Pain Disorder--involuntary vaginal muscle spasm which prohibits penile penetration and 4) Hypoactive Sexual Desire--patient lacks libido and sexual thoughts. N-methylnicotinate is a very potent vasodilator. When applied to the clitoris during stimulation, the clitoris becomes red, increases in size and has a "prickly" sensation. Women who previously have suffered from sexual dysfunction, report orgasms. Also, women who have had normal orgasms have reported increases in both the intensity and number of orgasms. The clitoris, which means "key" in the Greek language is the most important part of a woman's sexual anatomy. In order for a woman to have an orgasm, the corpora cavernous which is located within the clitoris, must become engorged with blood and enlarge. Web site: http://www.delphion.com/details?pn=US06403658__

•

Hormone replacement therapy drug formulations for topical application to the skin Inventor(s): Gyurik; Robert J. (Exeter, NH), Krauser; Scott F. (Tyngsboro, MA), Samour; Carlos M. (Bedford, MA) Assignee(s): MacroChem Corporation (Lexington, MA) Patent Number: 5,968,919 Date filed: October 16, 1997 Abstract: Topical alcoholic or aqueous alcoholic gels containing testosterone, progesterone, estradiol or other hormones have enhanced penetration through skin by including in the formulation 2-n-nonyl-1,3-dioxolane or other hydrocarbyl derivative of 1,3-dioxolane or 1,3-dioxane or acetal, as skin penetration enhancing compound. Excerpt(s): This invention relates to topical compositions for transdermal administration of a hormone through the skin of a patient and to the method for transdermally administering the hormone using the topical composition. All drugs must be administered in such a manner that they reach the intended site in the body in an optimal concentration (e.g., amount of drug per unit volume of blood) to achieve the desired effect at the proper time, and for an appropriate length of time. Customarily,

Patents 151

drugs are taken orally, injected, inhaled, or applied topically. These conventional routes of administration often fail to meet the stated objectives, however. For example, when drugs are absorbed into the blood stream by whatever route, peaks and valleys in the blood concentration of the drug occur and may cause undesirable effects (e.g., peak levels), or loss of activities (e.g., valleys). To meet these problems, a variety of approaches have been investigated. These include, for example, special drug coatings, combining the drug with other materials, suspensions or emulsions, and compressed tablets. Although these formulations attempt to control the release of drugs from their carriers, the desired effects are often not reproducible, may be subject to patient-topatient variations, and may not be suitable for prolonged periods of delivery, such as days or even months. Recent research has produced systems in which a drug is implanted in the body, released from skin sites, introduced in to the body by minipumps, and/or released in minute quantities through the skin. These innovative drug-delivery systems are improving drug effectiveness and also are opening opportunities for new pharmaceuticals. Web site: http://www.delphion.com/details?pn=US05968919__ •

Image forms and method for ameliorating male erectile dysfunction Inventor(s): Clarke; Anthony (Henley-on-Thames, GB), Green; Richard David (Marlborough, GB), Johnson; Edward Stewart (Ruscombe, GB) Assignee(s): R.P. Scherer Limited (GB) Patent Number: 6,342,246 Date filed: July 12, 1999 Abstract: The use of a pharmaceutical composition for oral administration comprising a carrier and active ingredient selected from a dopamine agonist, testosterone and mixtures thereof, the composition being in the form of a fast-dispersing dosage form designed to release the active ingredient rapidly in the oral cavity for the manufacture of a medicament for treatment of male erectile dysfunction. Excerpt(s): This invention relates to dosage forms and methods for ameliorating erectile dysfunction in male patients. More particularly, this invention relates to the use of fastdispersing dosage forms of drugs for amelioration of erectile dysfunction in male patients. A normal erection occurs as a result of a coordinated vascular event in the penis. This is usually triggered neurally and consists of vasodilatation and smooth muscle relaxation in the penis and its supplying arterial vessels. Arterial inflow causes enlargement of the substance of the corpora cavernosa. Venous outflow is trapped by this enlargement, permitting sustained high blood pressures in the penis sufficient to cause rigidity. Muscles in the perineum also assist in creating and maintaining penile rigidity. Erection may be induced centrally in the nervous system by sexual thoughts or fantasy, and is usually reinforced locally by reflex mechanisms. Male erectile dysfunction (MED) is defined as the inability to achieve and sustain an erection sufficient for intercourse. In any given case this can result from psychological disturbances (psychogenic), from physiological abnormalities in general (organic), from neurological disturbances (neurogenic), hormonal deficiencies (endocrine) or from a combination of the foregoing. Web site: http://www.delphion.com/details?pn=US06342246__

152 Testosterone

•

Immobilized and activity-stabilized complexes of LHRH antagonists and processes for their preparation Inventor(s): Deger; Wolfgang (Frankfurt, DE), Engel; Jurgen (Alzenau, DE), Losse; Gunter (Dresden, DE), Murgas; Sandra (Dresden, DE), Naumann; Wolfgang (Zug, DE), Reissmann; Thomas (Frankfurt, DE) Assignee(s): Asta Medica Aktiengesellschaft (Dresden, DE) Patent Number: 6,022,860 Date filed: March 26, 1998 Abstract: In this invention, a release-delaying system is to be developed for LHRH antagonists, in particular for cetrorelix, which allows the active compound to be released in a controlled manner over several weeks by complexation with suitable biophilic carriers.The acidic polyamino acids polyglutamic acid and polyaspartic acid were selected for complexation with cetrorelix. The cetrorelix polyamino acid complexes are prepared from aqueous solutions by combination of the solutions and precipitation of the complexes, which are subsequently centrifuged off and dried over P.sub.2 O.sub.5 in vacuo. If complexes having a defined composition are to be obtained, lyophilization proves to be a suitable method. The cetrorelix-carboxylic acid complexes were also prepared from the aqueous solutions.In the random liberation system, the acidic polyamino acids poly-Glu and poly-Asp showed good release-delaying properties as a function of the hydrophobicity and the molecular mass of the polyamino acid.In animal experiments, it was possible to confirm the activity of the cetrorelix-polyamino acid complexes as a depot system in principle. It is thus possible by complexation of cetrorelix with polyamino acids to achieve testosterone suppression in male rats over 600 hours. The release of active compound here can be controlled by the nature and the molecular mass of the polymers. Excerpt(s): The invention relates to activity-stabilized and release-delaying complexes of LHRH antagonists such as antide, antarelix, azaline, A-75998, ganirelix, Nal-Glu antagonist with polyamino acids, in particular polyglutamic acid and polyaspartic acid, and processes for the preparation thereof and pharmaceuticals comprising these. The peptide hormone-polyamino acid complexes prepared can be used in medicine, for example for the therapy of hormone-sensitive tumours, such as, for example, breast and prostate carcinoma, benign prostate hypertrophy and in gynaecology for the treatment of endometriosis, hysteroscopy and for the treatment of fertility disorders. In the Patent Specifications DD 257197, DD 269785 and DD 299265, for insulin and for other biologically active proteohormones, processes for the preparation of immobilized peptide preparations stabilized in their biological activities and modified in their pharmacological properties are described, whose most important feature is the complexation of the respective peptide with polyamino acids. Web site: http://www.delphion.com/details?pn=US06022860__

•

Intravaginal drug delivery devices for the administration of testosterone and testosterone precursors Inventor(s): Gilligan; Claire (Belfast, GB), Passmore; Clare (Belfast, GB) Assignee(s): Galen (Chemicals) Limited (Tallaght, IE) Patent Number: 6,416,780 Date filed: May 1, 2000

Patents 153

Abstract: This invention relates to an intravaginal shell or core drug delivery device suitable for administration to female humans or animals comprises testosterone or a testosterone precursor in a polymer matrix, surrounded by a sheath, and is capable of releasing the testosterone or testosterone precursor in a substantially zero-order pattern on a daily basis for at least three weeks. The device is intended to restore circulating testosterone levels to the normal physiol, range or to induce supratherapeutic testosterone levels. Excerpt(s): This invention relates to intravaginal drug delivery devices for the administration of testosterone and testosterone precursors to the human or animal female. The term `precursor` is intended to embrace those compounds which can be readily converted in vivo into testosterone, in which the products of such conversion are clinically and toxicologically acceptable and which compounds possess certain physicochemical properties as defined hereinbelow. In particular, it relates to intravaginal drug delivery devices for the administration of testosterone or a testosterone precursor at a substantially zero order rate over a prolonged period to alleviate or prevent the symptoms associated with testosterone deficiency or, alternatively, to induce supratherapeutic levels. The intravaginal drug delivery devices of the invention are particularly suitable for the alleviation or prevention of symptoms associated with testosterone deficiency either as a discrete treatment regimen or as an element of hormone replacement therapy in association with oestrogen or combined oestrogen/progestogen drug delivery devices. The clinical efficacy of testosterone replacement therapy, in association with exogenous oestrogen, has been reported from 1950 onwards [2]. The invention may, however, also have application to improve muscle mass and/or bone mass in patients with, for example, AIDS wasting syndrome or osteoporosis, respectively. In addition, the invention may have application as an antiproliferative agent for use against, for example, breast cancer, endometrial cancer, or endometriosis or, alternatively, to treat urogenital or vulval problems. Plasma concentrations of testosterone in the normal, pre-menopausal, healthy human female are between 0.5 and 2.3 nM (0.15 to 0.65 ng per ml) with a mid-cycle peak [1]. Testosterone deficiency in the premenopausal human female may occur due to disease, oophorectomy, adrenalectomy or traumatic injury. In the postmenopausal female, testosterone deficiency arises primarily from a reduced adrenal output of androstenedione, which is peripherally converted to testosterone in vivo [1]. Web site: http://www.delphion.com/details?pn=US06416780__ •

Maca and antler for augmenting testosterone levels Inventor(s): DeLuca; Daryl L. (Sugar Land, TX), DeLuca; Denis R. (Katy, TX), Sparks; William S. (Bellaire, TX) Assignee(s): Biotics Research Corporation (Rosenberg, TX) Patent Number: 6,093,421 Date filed: August 31, 1999 Abstract: Testosterone levels in men are increased by the oral administration of powdered maca and antler. Excerpt(s): In one aspect, the invention relates to a dietary supplement to increase testosterone levels, especially in humans. In another aspect, the invention relates to increasing plasma testosterone levels using a combination of the edible Andean tuber (Lepidium meyenii), commonly known as maca, with deer or elk antler. For a number of

154 Testosterone

reasons, elevated testosterone levels are associated with sense of enhanced well-being in men. Total testosterone levels decline with aging, about 0.2% per year in men, and testosterone replacement therapy has been used to improve the status of this hormone. A number of botanical preparations have been used to restore erectile function, including ginseng, Ginkgo biloba, yohimbine (Pausinytalia yohimbe), and muira puama (Ptychopetoalum olacoides) a South American plant. L-arginine, as a precursor of nitric oxide, and androstenedione also have application in male sexual function. Web site: http://www.delphion.com/details?pn=US06093421__ •

Means for treating prostate cancer Inventor(s): Engel; Jurgen (Alzenau, DE), Rawert; Jurgen (Alzenau, DE), Reissmann; Thomas (Frankfurt/Main, DE), Riethmuller-Winzen; Hilde (Frankfurt/Main, DE) Assignee(s): ASTA Medica Aktiengesellschaft (DE) Patent Number: 5,998,377 Date filed: April 9, 1998 Abstract: A regime for therapeutic management of a benign prostatic hyperplasia and prostatic cancer employs Cetrorelix alone or in combination with.alpha.-reductase inhibitors or.alpha.-receptor blocking agents. The regimen reduces the volume of the prostate and avoids the side effects associated with testosterone levels being in a castration range. Cetrorelix is administered at dosages between 0,5 mg/day and 20 mg/week or about 0.014 mg/kg body weight per day to 0,30 mg/kg body weight per week or at levels of about 25 to 120 mg of Cetrorelix per month or 0.376 mg/kg to 1.71 mg/kg per month. Cetrorelix can be administered with.alpha.-reductase inhibitors or.alpha.-receptor blocking agents. Excerpt(s): The invention is related to a method of treating benign prostate hypertrophy (BPH) and prostate cancer as well as to means of use therefor. Surgical elimination of the obstruction due to prostate enlargement is still considered the "gold standard" within the various modalities of treatment. Surgery, however, is not effective for all patients. Open operation or a transurethral resection results in no improvement in approximately 10 to 15% of the patients due to the presence of other causes, e.g. neurogenic bladder, infections. In addition, these invasive methods entail additional risks such as the occurrence of a retrograde ejaculation, diminished libido and urine incontinence. Less invasive methods exist, e.g. balloon dilatation and treatment with hyperthermia or microwaves. It has been established that an androgen-ablative therapy can yield positive results in the case of BPH; however, it is unclear whether full suppression should be achieved. The standard therapy for testosterone suppression in the case of prostate carcinomas consists in a bilateral orchiectomy. This is not generally acceptable for a benign sickness such as BPH. Another possibility involves influencing the effects of the sexual steroids through the use of LHRH analogues (LHRH=luteinizing hormonereleasing hormone). Web site: http://www.delphion.com/details?pn=US05998377__

Patents 155

•

Method and pharmaceutical formulation for treating benign prostatic hyperplasia Inventor(s): Zisapel; Nava (Tel Aviv, IL) Assignee(s): Neurim Pharamaceuticals (1991) Ltd. (Tel-Aviv, IL) Patent Number: 6,048,888 Date filed: November 24, 1997 Abstract: Benign prostatic hyperplasia (BPH) in male humans is treated by administering to a male patient in which such condition has been diagnosed, an effective BPH treating amount within the range of from 1 ng to 80 mg of melatonin, which may be in the form of a pharmaceutical formulation for use in treating BPH, which comprises, in combination a carrier, diluent or adjuvant, (1) an effective BPH treating amount of melatonin; and optionally (2) antiandrogens, antiestrogens, growth hormones and/or inhibitors of prostatal testosterone reductase; and/or (3) oxazepam or other melatonin receptor profile modifier. Excerpt(s): The present invention relates to a method for treating benign prostatic hyperplasia (BPH) and to a pharmaceutical formulation for this purpose. Melatonin is the principal hormone secreted by the pineal gland in all vertebrates. In all mammals studied to date, including humans, a nocturnal rise in the production of melatonin by the pineal gland is evident, regardless of whether the mammals are nocturnal or diurnal, and conversely, melatonin production by the body is acutely suppressed by light. Melatonin is involved in the coordination of photoperiod and physiological processes, e.g. in animals which use changes in the photoperiod to time their thermoregulation and reproduction, temporal signals to the thermoregulatory and reproductive systems are controlled by the daily rhythm in the duration of melatonin during the dark phase. Numerous studies have shown that melatonin has a potent influence on gonadal activity. The timing of melatonin administration has been shown to be crucial for its biological activities. E.g., while in the case of rats whose circadian rhythms are disrupted or arrhythmic in constant light, as well as in the case of rats free running in constant darkness, their rhythms are synchronized by daily melatonin injections, by contrast it has been found that continuous availability of melatonin in circulation, or injection of melatonin in the morning, sometimes prevents gonodal responses to melatonin in the afternoon. The inventor has shown, e.g. in Zisapel et al, Neuroendocrinology 40: 102 (1985), that the inhibition by melatonin of the stimulated release of dopamine from rat hypothalamus, was highest in the early photophase and lowest in the early afternoon. Web site: http://www.delphion.com/details?pn=US06048888__

•

Method of making nanoparticles of substantially water insoluble materials Inventor(s): Hassan; EmadEldin M. (Coventry House, Apt. B2 8048 Oxford Ave., Philadelphia, PA 19111) Assignee(s): none reported Patent Number: 6,623,761 Date filed: December 22, 2000 Abstract: This invention relates to a novel process of manufacture of nanoparticles of substantially water insoluble materials from emulsions. The emulsions have the ability to form a single liquid phase upon dilution of the external phase, instantly producing dispersible solid nanoparticles. The formed nanoparticles have average diameter of

156 Testosterone

about 10 to 200 nm and are suitable for drug delivery and targeting of water insoluble therapeutic or diagnostic agents. Examples of such agents are methotrexate, progesterone, testosterone, prednisolone, and ibuprofen. Such agents can be used in a wide range of therapeutic and diagnostic treatments including treatment for cancer, hormonal therapy, and pain management. Excerpt(s): This invention relates to nanoparticles of substantially water insoluble materials, methods of preparation, and use thereof. In particular, the invention relates to nanoparticles of therapeutic and diagnostic agents, method of preparation thereof, and pharmaceutically useful dispersions containing these nanoparticles. This invention further relates to methods of treatment using these nanoparticles. Nanoparticles of substantially water insoluble materials (i.e. materials that have water solubility of less than 0.1%) have a wide variety of applications, including therapeutic and diagnostic agents, paints, inks, dyes, and semiconductors. In most cases, performance of these nanoparticles dramatically improves as the nanoparticle size is reduced to 200 nanometers or less. Nanoparticles of therapeutic and diagnostic agents, in particular of a pharmaceutical compound ("drug") are customarily delivered with a solid or liquid carrier. Liquid containing nanoparticles such as emulsions, microemulsions and liposomes, however, usually suffer from the inherent physical instability of fluids resulting from globule dissociation. Solid polymeric or lipid nanoparticles have more structural stability, yet the rate of biodegradation of the nanoparticles and/or controlled release of the agent in the nanoparticles may not take place as intended, thereby adversely affecting optimal agent delivery and targeting. In addition, only a relatively small amount of the agent or drug can be encapsulated in fluid or solid carriers, requiring large, and sometimes impractical size dosages. Carrier-free nanoparticles, made entirely of a water insoluble therapeutic agent or drug, have been introduced as an alternative solution for the above limitations and drawbacks. There are two major techniques described in the prior art, to produce solid drug nanoparticles. These techniques are known as wet grinding, and antisolvent precipitation. Other general techniques for nanoparticle formation, such as solvent evaporation and emulsion polymerization, are either not suitable or have not proved to be successful in making carrier-free drug nanoparticles. Web site: http://www.delphion.com/details?pn=US06623761__ •

Method of sire selection using naloxone challenge tests and kits thereof Inventor(s): Fitzgerald; James A. (Columbus, MS), Lavoie; Verne A. (Dubois, ID), Perkins; Anne (East Helena, MT), Stellflug; John N. (Idaho Falls, ID) Assignee(s): Carroll College (Helena, MT), The United States of America as represented by the Secretary of Agriculture (Washington, DC) Patent Number: 6,193,949 Date filed: May 27, 1999 Abstract: There is variation in the sexual performance of male mammals. The purpose of this invention is to help identify high sexual performing males, particularly for livestock such as sheep. Testosterone is necessary for the normal execution of male behavior, but baseline levels are not predictive of libido. When a male mammal is given an injection of naloxone (an endorphin antagonist), his testosterone or LH response to the injection predicts whether he is a sexually active or inactive individual. This test is based on the premise that libido is more closely linked to the ability to secrete testosterone rather

Patents 157

than baseline concentrations. Naloxone challenge may be used as a general method to predict libido in male mammals. Excerpt(s): This application addresses the phenomenon of variation in sexual performance of male mammals. The purpose of this invention is to identify sexually active and non-working male mammals. In 1979, Gessa et al. gave injections of naloxone to sexually inactive male rats. The injections induced copulatory behavior. The authors suggested that endogenous opiates were the cause of the sexual inhibition and that the drug naloxone removed the opiate driven sexual inhibition. We gave naloxone to sexually inactive rams, but were unable to induce sexual behavior (Fitzgerald and Perkins, 1994). Unexpectedly, we noticed that the LH response to the naloxone treatment was greater in the sexually active rams versus the sexually inactive rams. So, although naloxone treatments did not alter libido or sexual performance, it did predict which rams would be most likely to demonstrate sexual activity based on their LH concentrations. There is a great deal of variation in the sexual performance of male sheep. In 1964, Hulet et al. described rams that failed to mate with estrus females during behavioral testing. Since then, several scientists, as well as producers, have observed poor sexual performing rams. Standardized sexual behavior tests have been developed that can evaluate sexual performance in rams (Kilgour and Whale, 1980). These behavioral tests involve observations of sexual activity. The average number of ejaculations that a ram achieves over several sexual performance tests correlates to pasture breeding efficiency (Perkins et al., 1992). These tests, however, are labor intense, costly and impractical for the producer to conduct. The purpose of this project was to develop a more practical tool (a drug test) that could be used by veterinarians or producers to predict sexual performance in rams or other species for which maximizing reproductive success is a concern. Web site: http://www.delphion.com/details?pn=US06193949__ •

Methods and compositions for the identification and assessment of prostate cancer therapies and the diagnosis of prostate cancer Inventor(s): Shyjan; Andrew W. (Nahant, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (Cambridge, MA) Patent Number: 6,506,607 Date filed: December 23, 1998 Abstract: The invention concerns two classes of differentially regulated genes: 1) genes that are more highly expressed in prostate cancer cells treated with testosterone than in untreated prostate cancer cells; and 2) genes that are more highly expressed in prostate cancer cells treated with bicalutamide, an anti-androgenic compound, than in untreated prostate cancer cells. Disclosed are methods for selecting and monitoring the effectiveness of therapeutic agents used for the treatment of prostate cancer. Also disclosed are methods for identifying novel therapeutic agents for the treatment of prostate cancer and methods and compositions for preventing, treating, and diagnosing prostate cancer. Excerpt(s): Prostate cancer is the most commonly diagnosed cancer in American men and the second most common cause of death from cancer in American men. Androgen withdrawal, by castration or through the use of an anti-androgenic drug, is the preferred treatment method for prostate cancer. Bicalutamide (casodex) is a relatively potent, orally active anti-androgenic drug. Approximately 80% of the prostate cancer patients

158 Testosterone

treated with bicalutamide respond to the treatment; however, most patients eventually relapse. Web site: http://www.delphion.com/details?pn=US06506607__ •

Methods of treatment for premature ejaculation in a male Inventor(s): Day; Wesley W. (Old Lyme, CT), Lee; Andrew G. (Old Lyme, CT), Thompson; David D. (Gales Ferry, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,512,002 Date filed: January 10, 2001 Abstract: This invention relates to methods and pharmaceutical compositions useful in the treatment of conditions that are responsive to the elevation of testosterone levels in the body and the use of estrogen agonists/antagonists for the manufacture of medicaments for the treatment of conditions that are responsive to the elevation of testosterone levels in the body. The compositions are comprised of an estrogen agonist/antagonist and a pharmaceutically acceptable vehicle, carrier or diluent. These compositions are effective in treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and are effective in increasing libido in female subjects including post-menopausal women. In the case of male subject sexual dysfunction, the compositions may also include a compound which is an elevator of cyclic guanosine 3',5'-monophosphate (cGMP). Additionally, the compositions are effective in other conditions whose etiology is a result of testosterone deficiency or which can be ameliorated by increasing testosterone levels within the body. Methods of the invention include the treatment of conditions that are responsive to elevation of testosterone levels such as treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and the increase of libido of female subjects including post-menopausal women. The methods of treatment are effective while substantially reducing the concomitant liability of adverse effects associated with testosterone administration. Excerpt(s): This invention relates to compositions and methods for treating conditions responsive to testosterone administration including male subject sexual dysfunction, lowered libido in female subjects including post-menopausal women and timidity in female subjects including post-menopausal women. The compositions and methods utilize estrogen agonist/antagonist compounds. Testosterone, the principal androgen, is synthesized in the testis, the ovary, and the adrenal cortex. In the circulation, testosterone serves as a prohormone for the formation of two classes of steroids: 5.alpha.-reduced androgens, which act as the intracellular mediators of most androgen action, and estrogens, which enhance some androgenic effects and block others. Thus the net effect of the action of endogenous androgens is the sum of the effects of the secreted hormone (testosterone), its 5.alpha.-reduced metabolite (dihydrotestosterone, and its estrogenic derivative (estradiol). Adequate amounts of these hormones are required for proper physical development and physiological homeostasis. When diminished or absent from the body, pathological conditions can arise in the body due to a testosterone deficiency which are treatable by testosterone replacement. Additional conditions can be treated or ameliorated through the supplementation of endogenous testosterone. Conditions responsive to testosterone elevation may arise in women as a result of menopause. Menopause occurs naturally at an average age of 50 to 51 years in the USA. As ovaries age, response to pituitary gonadotropins (follicle-stimulating

Patents 159

hormone [FSH] and luteinizing hormone [LH]) decreases, initially resulting in shorter follicular phases (thus, shorter menstrual cycles), fewer ovulations, decreased progesterone production, and more irregularity in cycles. Eventually, the follicle fails to respond and does not produce estrogen. The transitional phase, during which a woman passes out of the reproductive stage, begins before menopause. It is termed the climacteric or perimenopause, although many persons refer to it as menopause. Web site: http://www.delphion.com/details?pn=US06512002__ •

Phenylsubstituted 4-azasteroid fluoroderivatives Inventor(s): Di Salle; Enrico (Milan, IT), Nesi; Marcella (Milan, IT), Panzeri; Achille (Merate, IT) Assignee(s): Pharmacia & Upjohn, S.p.A. (Milan, IT) Patent Number: 6,114,345 Date filed: April 28, 1999 Abstract: Compounds of formula (I), wherein: the symbol ---- represents a single or a double bond; R is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; R.sub.f and R'.sub.f, each independently, are C.sub.1 -C.sub.4 alkyl groups substituted by one or more fluorine atoms; and R.sub.1 and R.sub.2, each independently, are selected from: a hydrogen atom; a phenyl group; a C.sub.1 -C.sub.4 alkyl group unsubstituted or substituted by one or more fluorine atoms; a halogen atom; a cyano (CN) group; a group OR.sub.4, wherein R.sub.4 is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; a group SR.sub.5, wherein R.sub.5 is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; and a group COR.sub.6, wherein R.sub.6 is a group OR.sub.4 in which R.sub.4 is as defined above or a C.sub.1 -C.sub.4 alkyl group unsubstituted or substituted by one or more fluorine atoms. They are useful as testosterone 5a-reductase inhibitors. Excerpt(s): The present invention relates to phenylsubstituted 4-azasteroid fluoroderivatives and to a process for their preparation. Moreover, the present invention relates to pharmaceutical compositions containing said phenylsubstituted 4-azasteroid fluoroderivatives and to their use as inhibitors of androgen action, by means of testosterone 5.alpha.-reductase inhibition. In certain androgen responsive tissues the action of testosterone is mediated primarily through its 5.alpha.-reduced metabolite, dihydrotestosterone (DHT) (Bruchowsky N., Wilson J. D.; J. Biol. Chem. 243, 5953, 1968). The conversion of testosterone to dihydrotestosterone is catalyzed by the enzyme 5.alpha.-reductase and if 5.alpha.-reductase is inhibited, the formation of dihydrotestosterone is reduced and its specific androgenic effect is attenuated or prevented. The 5.alpha.-reductase inhibitors may find medical application for the treatment of hyperandrogenic conditions, e.g. certain prostatic diseases, such as benign prostatic hyperplasia and prostatic cancer, and certain skin-hair conditions, such as acne, seborrhoea, female hirsutism and male pattern baldness (Siiteri P. K., Wilson J. D., J. Clin. Invest. 49, 1737, 1970; Price V. H., Arch. Dermatol. III, 1496, 1975; Sandberg A. A., Urology 17, 34, 1981). Also breast cancer treatment can take advantage from use of 5.alpha.-reductase inhibitors as the said tumour is known to be aggravated by presence of androgens. Androst-4-en-3-one-17.beta.-carboxylic acid and its methyl ester (Voigt and Hsia, Endocrinology, 92, 1216 (1973); Canadian Patent No. 970,692) are among the first steroidic compounds described as 5.alpha.-reductase inhibitors. Web site: http://www.delphion.com/details?pn=US06114345__

160 Testosterone

•

Preparation for the treatment of metabolic syndrome containing human growth hormone in combination with a cortisol synthesis inhibitor Inventor(s): M.ang.rin; Per (Goteborg, SE) Assignee(s): Cortendo AB (Vastra Frolunda, SE) Patent Number: 6,274,582 Date filed: August 24, 1999 Abstract: Human growth hormone is used in combination with a cortisol synthesis inhibitor, in particular ketoconazole, for prevention or treatment of conditions related to Metabolis Syndrome (Neuroendocrine Syndrome). Administration can be supplemented by a sex hormone selected from testosterone and natural or synthetic estrogen. Also disclosed are corresponding pharmaceutical compositions. Excerpt(s): The present invention relates to the prevention and treatment of Metabolic Syndrome. More particularly, the invention relates to medicaments, preparations and treatments comprising cortisol synthesis inhibitors and growth hormone for treating the conditions which comprise the Metabolic Syndrome. In both men and women, visceral (intra-abdominal) fat accumulation is associated with an increased risk of the development of non-insulin dependent diabetes, myocardial infarction, stroke and other arteriosclerotic diseases and their associated risk factors, including insulin resistance, elevated blood lipids, glucose and hypertension. The clustering of these risk factors has been designated `Metabolic Syndrome`, also called `Syndrome X`, the `Insulin Resistance Syndrome` or the `Deadly Quartet`. This syndrome is also characterised by one or more endocrine disturbances and is therefore also called `Neuro-endocrine Syndrome` (Marin, P. Neuroendocrine News, 21(3) 1996, 2). These disturbances include low serum levels of sex steroids (testosterone in men, and estrogens in women), signs of a decreased action of growth hormone, and an excessive secretion of cortisol. The latter has been shown clinically as a major causative process for the development of Metabolic Syndrome as demonstrated by successful treatment with the cortisol synthesis inhibitor ketoconazole (WO 96/04912). Conditions related to Metabolic Syndrome include diabetes mellitus type II (IDDM), non-insulin dependent diabetes (NIDDM), myocardial infarction, stroke and other arteriosclerotic diseases as well as the risk factors for these diseases, insulin resistance in general, abdominal obesity caused by accumulation of intra-abdominal fat, elevated serum lipids, and raised diastolic and/or systolic blood pressure. Web site: http://www.delphion.com/details?pn=US06274582__

•

Rhodiola and used thereof Inventor(s): Xiu; Rulin (2010 Kalorama Rd., NW., Suite 44, Washington, DC 20009) Assignee(s): none reported Patent Number: 6,399,116 Date filed: April 28, 2000 Abstract: The present invention relates to Rhodiola, preferably Rhodiola crenulata, to treat various conditions and diseases in mammals. Rhodiola crenulata is a Tibetan herb which has been discovered to have highly useful and beneficial properties heretofore unknown. Rhodiola crenulata is especially preferred to enhance blood oxygen levels, to enhance working capacity and endurance, to enhance memory and concentration, to

Patents 161

enhance cardiac and cardiovascular function, to provide antioxidant effects, to protect against oxidation, to modulate testosterone and estradiol levels, to modulate sleep, and to enhance sexuability, such as improve sexual performance. Excerpt(s): The present invention relates to compositions, articles of manufacture, extracts, compounds, methods of use, methods of treatment, methods of preparation, etc., which relate to plants of the genus Rhodiola, preferably Rhodiola crenulata, which have a variety of useful and beneficial effects, including, e.g., to enhance blood oxygen and nutrients levels, e.g., through enhancing oxygen transport, to enhance working capacity and endurance, to reduce muscle fatigue, to enhance memory and concentration, to reduce stress, to enhance cardiac and cardiovascular function, to provide antioxidant effects, to protect against oxidation, to provide anti-cancer effects, to promote DNA repair, to provide anti-radiation effects, to protect against radiation, to reduce inflammation, to increase insulin, to decrease levels of glucagon, to reduce histamine release, to reduce allergic reactions, preferably, to modulate testosterone levels, and to modulate sleep, especially to promote sleep, to modulate blood lipids, preferably, e.g., to lower cholesterol levels, to promote weight loss, and to enhance sexuability, such as improve sexual performance. Rhodiola crenulata is a species of Rhodiola which grows mostly in Tibet and south west of China on the altitude between 3400 meters to 5600 meters. It has been used in Tibetan medicine for more than 1000 years for uses that have been limited to curing lung inflammation and cough, for stopping and activating blood, and for treating external wounds and burns. It has been discovered herein that Rhodiola crenulata has other beneficial properties that make it useful for a variety of conditions and diseases, as mentioned above and below. Rhodiola is a diverse genus of plants which includes more than 50 different species, including, e.g., algida, arctica, crenulata, elongata, gelida, imbricataishidae, iremelica, kirilowii, linearifolia, phariensis, pinnatifida, quadrifida, aff. quadrifida, rosea, sachalinensis, and wolongensis. These species vary from each other widely, differing in, e.g., chromosome number (e.g., Makoto et al., Journal of Japanese Botany, 70(6):334-338, 1995), chemical composition, morphology, medicinal properties, developmental stages (e.g., Ishmuratatova and Satsyperova, Rastitel'nye Resursy., 34(1):3-11, 1998), geographical distribution, etc. Scientific studies (e.g. Peng et al, Chinese Herb Medicine (1995), 26(4): 177-179, and Wang et al, Acta Phrmaceutica Sinica(1992), 27(2): 117-120) indicate constituents of Rhodiola crenulata include, e.g., salidroside, tyrosol,.beta.-sitosterol, gallic acid, pyrogallol, crentulatin, rhodionin, rhodiosin, among which, crenulatin, e.g., is found only in R. crenulata and has not been found in any other Rhodiola species. Rhodiosin and rhodionin exists in some, but not all, Rhodiola species. Web site: http://www.delphion.com/details?pn=US06399116__ •

Testosterone compounds and use for the protection of neurons Inventor(s): Gordon; Katherine D. (Winchester, MA), Leonard; Robert (Swampscott, MA), Simpkins; James W. (Gainesville, FL) Assignee(s): Apollo Biopharmaceutics, Inc. (Cambridge, MA), University of Florida Research Foundation, Inc. (Gainesville, FL) Patent Number: 6,172,088 Date filed: November 24, 1998 Abstract: Androgens and their derivates and analogs, such as anabolic agents, are characterized by at least one substituent or substituent grouping with radical trapping properties. These compounds are used as androgen or anabolic agent substitutes or

162 Testosterone

therapeutical agents for treating androgen defficiency; for treating benign prostate hypertrophy and prostate carcinome, in particular with a testosterone-based compound; for treating osteoporosis, in particular post-menopausal osteoporosis in women, preferably associated with estrogen and/or gestagens; for treating brain oedema induced by vasculary or ischemic troubles, subarachnoidal bleeding, ischemic shock and cerebral insult; for treating asthma in its various forms, for treating Alzheimer's disease, Parkinson's disease; for organ transplants; and for treating androgen-dependent and non androgen-dependent malign neoplasia Excerpt(s): The present invention relates to novel methods for conferring neuroprotection on a subject that relies on administering an effective dose of at least one testosterone inhibitor. Neurodegenerative diseases have a major impact on society. For example, approximately 3 to 4 million Americans are afflicted with a chronic neurodegenerative disease known as Alzheimer's disease. Other examples of chronic neurodegenerative diseases include diabetic peripheral neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, Huntingdon's disease and Parkinson's disease. Not all neurodegenerative diseases are chronic. Some acute conditions arise from stroke, schizophrenia, cerebral ischemia resulting from surgery and epilepsy as well as hypoglycemia and trauma resulting in injury of the brain, peripheral nerves or spinal cord. There is a need for improved therapeutic agents and methods for reversing or retarding neuronal damage associated with each of these conditions. Neurodegenerative diseases and aging are characterized by a wide range of symptoms which vary in severity and range from individual to individual. For example, Alzheimer's disease is characterized by symptoms such as depression, aggression, impairment in short-term memory, impairment in intellectual ability, agitation, irritability and restlessness. Web site: http://www.delphion.com/details?pn=US06172088__ •

Testosterone derivative Inventor(s): D.; Dirk Leysen (Lommel, BE), Van Der Voort H.A.A; Hendrikus Adrianus Antonius (Veghel, NL) Assignee(s): Akzo Nobel N.V. (Arnhem, NL) Patent Number: 6,437,158 Date filed: December 18, 2000 Abstract: The invention is drawn to (7a, 17b)-7-methyl-17-(1-oxoundecyl)oxy-estr-4-en3-one, (MENT undecanoate), their pharmaceutical formulation and method of use is described. Unexpected results of the said compound compared with testosterone undecanoate is disclosed. Excerpt(s): This application is a 371 of PCT/EP99/04102, filed on Jun. 14, 1999. The invention is in the field of androgenic hormones, more specifically derivatives of testosterone. Testosterone derivatives are known. Testosterone itself, the natural male hormone, has many known drawbacks as far as methods of administration are concerned. It has a short-lasting activity, is insoluble in the usual pharmaceutically acceptable media, and is not very potent. The more potent dihydrotestosterone (5.alpha.-reduced form of testosterone) is considered a health-risk, notably for the prostate. A somewhat better soluble derivative is testosterone undecanoate, which is known as the active substance in the product Andriol.RTM. Web site: http://www.delphion.com/details?pn=US06437158__

Patents 163

•

Therapy apparatus with laser irradiation device Inventor(s): Wilden; Lutz (Hofackerweg 16a, D-94051 Hauzenberg, DE) Assignee(s): none reported Patent Number: 6,358,272 Date filed: August 25, 1999 Abstract: The present invention refers, in general, to therapy apparatuses with a lowlevel laser irradiation device. In particular, the invention relates to an oral hygiene apparatus, an apparatus for therapy of rhinitis and acne, an apparatus for stimulation of testosterone, an inner-ear-disorder treatment apparatus for therapy of a chronic complex inner-ear disorder, an apparatus for stimulation of the central nervous system, an apparatus for therapy and prophylaxis of decubitus, as well as an apparatus for biostimulation of plants. Excerpt(s): The present invention relates in general to therapy apparatuses with a laser irradiation device. In particular, the invention relates to an oral hygiene apparatus, an apparatus for therapy of rhinitis and acne, an apparatus for the stimulation of testosterone in the scrotum, an inner-ear-disorder treatment apparatus for therapy of a chronic complex inner-ear disorder, an apparatus for stimulating the central nervous system, an apparatus for therapy and prophylaxis of decubitus, as well as an apparatus for biostimulation of plants. The oral hygiene apparatuses developed further by the invention are preferably such apparatuses which have a handle that is equipped with a mouthpiece which can be inserted into the mouth, with an oral hygiene device being located at its mouth-side end. Pursuant to a further development of the invention, it preferably covers such oral hygiene apparatuses that are electrically operated. Such an electrically operated oral hygiene apparatus is preferably a water pick or also an electric toothbrush. The advantages of oral hygiene apparatuses operated in such a way, with regard to keeping the teeth clean and/or massaging the gums, are sufficiently known and therefore will not be discussed further here. In dental practices, so-called "low-level laser irradiation apparatuses" have been increasingly in use; their purpose of use is particularly the therapy and prophylaxis of periodontia, as well as the therapy and prophylaxis of stomatitis aphtosa, of herpes diseases of the lips (herpes labialis), and of the mucosa of the mouth, as well as of acne. The prefix "low-level" ("low level") for such therapeutic laser irradiation apparatuses was coined because the output, i.e. the dosage of the laser beam given off is dimensioned so that it causes no thermal effect of any kind on the body part that it impacts, in other words particularly the gums. Web site: http://www.delphion.com/details?pn=US06358272__

•

Transdermal application of naturally occurring steroid hormones Inventor(s): Shaak; Carolyn V. (1093 Beacon St., Brookline, MA 02146) Assignee(s): none reported Patent Number: 6,228,852 Date filed: July 8, 1997 Abstract: The invention features a physiologically acceptable cream that contains estrogen, progesterone, and testosterone molecules that are identical to the estrogen, progesterone, and testosterone molecules naturally produced by the human body. The

164 Testosterone

cream may be self-administered to the skin and is useful as a means of hormone replacement therapy, which may begin at around the time of menopause. Excerpt(s): This invention relates to hormone replacement therapy. Progesterone is a steroid hormone that is produced by the ovaries during a woman's child-bearing years. Progesterone is also made, although in smaller amounts, by the adrenal glands in both sexes and by the testes in males. An astonishing variety of physiological functions are mediated by progesterone (See e.g., Lee, 1993, Natural Progesterone, BLL Publishing, Sebastopol, Calif.). For example, progesterone, which surges following ovulation, maintains the secretory endometrium and thus, helps to ensure the survival of the embryo and fetus. It also acts as a diuretic, an antidepressant, and as a precursor of corticosteroids and of other sex hormones, notably estrogen and testosterone. There is also evidence that progesterone affords protection against loss of libido, osteoporosis, endometrial cancer, breast cancer, and fibrotic cysts. When the child-bearing years draw to a close, every woman experiences a decline in the production of progesterone, and consequently, a decline in all of the hormones that are synthesized from progesterone. This decline significantly and negatively affects both life-span and quality of life (Ettinger, 1996, Obst. and Gyne. 87:6-12; Karlberg et al., 1995, Acta. Obstet. Gynecol. Scand. 74:367-372). In addition to the uncomfortable symptoms, such as hot flashes, that are frequently experienced at around the time of menopause, there is an increase in the prevalence of life-threatening conditions, including heart disease, osteoporosis, and brain ischemia (more commonly called a "stroke"; Hunt et al., 1990, Br. J. Obstet. Gynecol. 97:1080-1086). These conditions exact a high personal price and consume significant medical resources. Postmenopausal osteoporosis, the most common metabolic bone disorder in the United States, is the underlying cause of over 1.3 million fractures, at an estimated cost of over $10 billion annually. Web site: http://www.delphion.com/details?pn=US06228852__ •

Transdermal device for the delivery of testosterone Inventor(s): Hedenstrom; John C. (St. Paul, MN), Husberg; Michael L. (West St. Paul, MN), Scholz; Matthew T. (Woodbury, MN), Wilking; Shari L. (Inver Grove Heights, MN) Assignee(s): 3M Innovative Properties Company (St. Paul, MN) Patent Number: 6,132,760 Date filed: February 27, 1998 Abstract: A transdermal delivery device including an adhesive layer that contains a therapeutically effective amount of testosterone and a delivery enhancing adjuvant comprising a terpene. Excerpt(s): The present invention relates to transdermal drug delivery devices. In another aspect this invention relates to pharmaceutical formulations containing testosterone. Transdermal drug delivery devices are designed to deliver a therapeutically effective amount of drug across the skin of a patient. Devices known to the art include reservoir type devices involving membranes that control the rate of drug release to the skin and devices involving a dispersion of the drug in a matrix such as a pressure sensitive adhesive. The skin, however, presents a substantial barrier to ingress of foreign substances into the body. It is therefore often desirable or necessary to incorporate certain materials that enhance the rate at which the drug passes through the skin. However, the type of device, the transdermal flux rate that is suitable, and the

Patents 165

suitable formulation components are dependent upon the particular drug to be delivered. Testosterone is the main androgenic hormone formed in the testes. Testosterone therapy is currently indicated for the treatment of male hypogonadism. It is also under investigation for the treatment of wasting conditions associated with AIDS and cancer, testosterone replacement in men over the age of 60, osteoporosis, combination hormone replacement therapy for women and male fertility control. Web site: http://www.delphion.com/details?pn=US06132760__ •

Use of 4-androstene-3alpha,17 beta-diol to increase testosterone levels in humans Inventor(s): Llewellyn; William Charles (P.O. Box 1162, Sound Beach, NY 11789) Assignee(s): none reported Patent Number: 6,451,782 Date filed: February 12, 2002 Abstract: This invention discloses methods of administering 4-Androstene3alpha,17beta-diol in order to increase testosterone levels in humans. As men age, a decline in androgenic hormone levels is typically noted, possibly resulting in muscle mass, bone density and energy loss. Various methods have therefore been developed to supplement androgens for men with declining levels. Some such have focused on the use of direct metabolic precursors to testosterone, as a means of raising levels of this androgen in humans. This invention is an improvement over the use of the precursor 4Androstene-3,17-beta-diol, in that the subject of this invention displays a much higher ability to convert to testosterone in the human body. This may be a very advantageous trait for aging men who require a safe and effective way to treat subnormal androgen levels. Excerpt(s): Testosterone is considered to be the primary male androgen. It is responsible for the development and maintenance of male sexual characteristics, including external virilization, sexual maturity at puberty, spermatogenesis, sexual behavior/libido and erectile functioning. It also supports bone and muscle tissue growth, and remains vital to ones health and well being throughout life. After physical maturity, men often notice a slow decline in the level of testosterone produced by the body. Dubbed andropause, subnormal androgen levels can lead to a decline in muscle mass, libido, sexual functioning and overall sense of well being later in life. In many instances this indicates a need for some form of androgen replacement. A number of methods have been developed to restore androgen concentration in humans with declining levels. Several injectable esterified testosterone preparations have been fashioned that allow a slow release of hormone into the blood stream over the course of several days to weeks for example, however all provide inconsistent dosing as there is great variance in hormone release from the site of injection, such that a short supraphysiological rush may eventually be followed by days of subnormal hormone concentrations. The buildup of estrogens due to the natural process of aromatization may exaggerate the side effects to such medication, particularly at times when testosterone levels are abnormally high, as supraphysiological levels of estrogens in the male body have been linked to gynecomastia (female breast tissue development), water retention and edema, and increased fat deposition. Also a number of synthetic oral androgen derivatives have been developed including methyltestosterone, fluoxymesterone and stanozolol. All such compounds are alkylated at the 17.sup.th carbon position (alpha orientation), an alteration that inhibits reduction of the steroid to inactive 17-ketosteroid form. While this greatly improves oral bioavailability of the compound, this alteration has also been

166 Testosterone

shown to place stress on the liver, in some instances resulting in organ damage. Although the use of a c-17 alpha alkylated oral androgen may prove much more comfortable for the patient in terms of dosing and control over blood hormone level compared to an injectable preparation, the possible risk of developing complications with liver functions may make them much less useful for androgen replacement compared to injectable preparations, particularly for extended periods of therapy. Web site: http://www.delphion.com/details?pn=US06451782__ •

Water soluble amine esters of testosterone for intranasal administration Inventor(s): Hussain; Anwar A. (Lexington, KY) Assignee(s): University of Kentucky (Lexington, KY) Patent Number: 6,423,701 Date filed: January 25, 1996 Abstract: The present invention provides novel water soluble testosterone analogs. These testosterone analogs are suitable for intranasal administration to patients requiring increased plasma testosterone levels. The present invention also provides pharmaceutical compositions containing the testosterone analogs of the present invention. The present invention further provides a method of increasing plasma testosterone levels in patients in need of such treatment comprising the intranasal administration of the water-soluble testosterone analogs and pharmaceutical compositions of the present invention. Excerpt(s): This invention relates generally to novel water-soluble prodrugs of testosterone suitable for intranasal administration to mammals, including humans, in need of testosterone replacement therapy. More specifically, this invention relates to a water-soluble form of testosterone which is suitable for intranasal administration. This invention also relates to a testosterone replacement therapy which comprises intranasal administration of one or more of the water-soluble forms of testosterone of the present invention. Testosterone (17.beta.-hydroxyandrost-4-en-3-one) and its metabolite, dihydrotestosterone, are the primary endogenous androgenic hormones (androgens). Endogenous androgens are responsible for the normal growth and development of the male sex organs and for development and maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature, and fat distribution. These compounds also cause retention of nitrogen, sodium, potassium phosphorous, and decreased urinary excretion of calcium. Androgens have also been reported to increase protein anabolism and decrease protein catabolism. Androgens are responsible for the growth spurt of adolescence and for the eventual termination of linear growth brought about by fusion of the epiphyseal growth centers. In children, exogenous androgens accelerate linear growth rate but may cause a disproportionate advancement in bone maturation. Androgens have been reported to stimulate the production of red blood cells by enhancing the production of erythropoietin. Web site: http://www.delphion.com/details?pn=US06423701__

Patents 167

Patent Applications on Testosterone As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to testosterone: •

17-methylene steroids, process for their production and pharmaceutical compositions that contain these compounds Inventor(s): Droescher, Peter; (Weimar, DE), Elger, Walter; (Berlin, DE), Hillisch, Alexander; (Jena, DE), Kaufmann, Gunter; (Jena, DE), Menzenbach, Bernd; (Jena, DE), Muller, Gerd; (Jena, DE), Schweikert, Hans-Udo; (Bonn, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020091112 Date filed: January 25, 2002 Abstract: The invention relates to 17-methylene steroids, process for their production and pharmaceutical compositions that contain these compounds.The compounds according to the invention have a hybrid-type profile of action in the sense that they act as inhibitors of 5.alpha.-reductase and simultaneously as gestagens. They are therefore suitable for treating diseases that are the result of elevated androgen levels in certain organs and tissues in men and women. Together with other hormonal substances, such as an estrogen, testosterone or a strong androgen, the compounds according to the invention are suitable as contraceptive agents for women and for men. Excerpt(s): This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/243,281 filed Oct. 26, 2000. The invention relates to 17methylene steroids, process for their production and pharmaceutical compositions that contain these compounds. The compounds according to the invention have a hybridtype profile of action in the sense that they act as inhibitors of 5.alpha.-reductase and simultaneously as gestagens. They are therefore suitable for treating diseases that are the result of elevated androgen levels in certain organs and tissues in men and women. Together with other hormonal substances, such as an estrogen, testosterone or a strong androgen, the compounds according to the invention are suitable as contraceptive agents for women and for men. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Anti-aging/menopause symptoms relief using ganoderma lucidum spores Inventor(s): Chung, Chee-Keung; (Kowloon, HK), Tong, Siu Kan; (Kowloon, HK) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030054014 Date filed: August 21, 2002 Abstract: The present invention provides a method for preventing/slowing aging and/or reducing menopause symptoms in humans by orally administering an effective

10

This has been a common practice outside the United States prior to December 2000.

168 Testosterone

amount of germination-activated Ganoderma lucidum spores (GLSs) to humans. The treatment for menopause is especially effective in male patients. GLSs are effective as an antioxidant to reduce free radical damage, particularly by increasing the amount of the reduced form glutathione (GSH) and the superoxide dismutase (SOD) activity. GLSs can also increase testosterone level in blood and improve depression, particularly geriatric depression, in elderly male patients. Excerpt(s): The present application is a continuation-in-part (CIP) of U.S. patent application Ser. No. 09/802,862, filed on Mar. 12, 2001, which is a divisional application of U.S. patent application Ser. No. 09/524,508, filed on Mar. 13, 2000 and issued as U.S. Pat. No. 6,316,002, which in turn claims the priority of U.S. provisional application No. 60/158,377, filed on Oct. 12, 1999, wherein all of the U.S. priority applications are herein incorporated by reference. The present invention relates to a method for preventing/slowing an aging process and/or reducing/relieving menopause symptoms in humans by orally administering an effective amount of germination-activated Ganoderma lucidum spores ("GLSs") to humans. The anti-aging effect of GLSs is primarily derived from its being an antioxidant for free radical protection. GLSs also reduce and/or relieve symptoms associated with menopause, particularly male menopause, which are partially due to aging. Symptoms associated with male menopause include fatigue, anorexia, palpitation, forgetfulness, irritation, depression, and/or impotence. The free radical theory of aging was first proposed by Dr. Denham Harman in 1956. It is now recognized that living cells continuously produce free radicals during their normal functions such as producing energy. Free radicals also come from smoking, radiation, sunlight and other factors in the environment. Endogenous and exogenous free radicals are highly reactive substances, capable of reacting irreversibly with many biological molecules, producing random changes, and causing progressive deterioration of the biological system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Chemo- and radiation-sensitization oligodeoxynucleotides

of

cancer

by

antisense

TRPM-2

Inventor(s): Gleave, Martin; (Vancouver, CA), Miyake, Hikeaki; (Vancouver, CA), Nelson, Colleen; (Surrey, CA), Rennie, Paul S.; (Richmond, CA), Zellweger, Tobias; (Basel, CH) Correspondence: Oppedahl And Larson Llp; P O Box 5068; Dillon; CO; 80435-5068; US Patent Application Number: 20030158130 Date filed: September 28, 2001 Abstract: Administration of antisense oligodeoxynucleotides (ODN) targeted against the testosterone-repressed prostate message-2 (TRPM-2) gene can reduce the amount of TRPM-2 in renal cell cancer (RCC) cells and other cancer cells, and as a result enhance chemosensitivity of these cells to chemotherapy agents and radiation. Thus, for example, the sensitivity of renal cell cancer cells to a chemotherapeutic agent can be increased by exposing renal cell cancer cells to a chemotherapeutic agent and an agent which reduces the amount of TRPM-2 in the renal cell cancer cells. This provides an improved method for treatment of renal cell cancer, which is generally resistant to treatment with known chemotherapy agents. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/913,325, which is a 371 National Stage of PCT/US00/0487, which are incorporated

Patents 169

herein by reference. This application also claims the benefit of U.S. Provisional Application No. 60/236,301, filed Sep. 28, 2000 which is incorporated herein by reference. This application relates to a method and compositions for chemosensitization and radiosensitization of cancer cells through administration of compositions, such as antisense oligonucleotides, which reduce the amount of TRPM-2 in the cells. The invention is of particular applicability to cancers such as renal cell carcinoma (RCC) which are resistant to chemo- and radiotherapy. Treatment of cancers by chemotherapy or radiotherapy frequently results in side effects because the therapy used is not specific to the cancer and kills non-cancerous cells as well. Where the cancer is resistant to the therapy, the dosage used must be increased, and the side effects become more pronounced. Thus, as a general principal, it would be desirable to be able to increase the sensitivity of cancer cells to chemotherapy and radiotherapy so that lower effective dosages could be employed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Clitoral sensitizing arrangements Inventor(s): Thompson, Ronald J.; (Ft. Thomas, KY) Correspondence: Donald N. Halgren; 35 Central Street; Manchester; MA; 01944-1311; US Patent Application Number: 20020165429 Date filed: December 14, 2000 Abstract: This invention relates to an arrangement for the treatment of clitoral dysfunction of a female. Such clitoral dysfunction may be described as an excessively long arousal time from initiation of foreplay to complete clitoral erection, a decreased intensity of a woman's orgasm and a lack of multiple orgasms. The treatment for these clitoral dysfunctionalities include augmentation of testosterone for the female to supplement low testosterone levels and to improve the libido of the female and the treatment also includes a subsequent or concurrent application of a compound of menthol and L-Arginine applied to the clitoris of the female. Excerpt(s): This invention relates to a method to increase the physiological actions of a topically applied clitoral compound by prior or concurrent administration of an oral or transdermal agent to increase central and peripheral female libido, and is a continuation-in-part application of my co-pending U.S. patent application Ser. No. 09/520,110 which is a continuation-in-part application of my co-pending application Ser. No. 09/468,959 which is a continuation-in part application of my co-pending application Ser. No. 09/414,250, which is a continuation-in-part application of my copending application Ser. No. 09/340,227, all of which are herein incorporated by reference, in their entirety. Clitoral arousal and responsiveness are the primary factors in sexual enjoyment for females. Decreased clitoral sensitivity, and responsiveness are related to normal aging, relative or absolute estrogen and testosterone deficiency, (either as a consequence of medicines or aging), and by a host of vascular conditions such as diabetes and hypertension. Multiple laboratory and clinical research endeavors have been directed primarily toward male erectile dysfunction (ED), yielding not only an understanding of the erection physiology, but also medications to treat ED, such as VIAGRA.RTM., a prescription medication marketed for that problem, by Pfizer, Inc. Very little research has been initiated to understand or address female physiological sexual unresponsiveness. However, since the penis and the clitoris are analogous anatomical structures, the basic cellular and physiological knowledge about male penile erections translates to functions of the clitoris. Female clitoral dysfunction is extremely

170 Testosterone

difficult to document and quantify. A number of modalities, such as Doppler blood flow, precise temperature measurements, and actual imaging measurements, have been employed to attempt to define clitoral erection have been reported in the literature-all with results unsatisfactory for meaningful research. Estimates that 15 million U.S. men suffer from erectile dysfunction have been reported in the literature. A recent article in the Feb. 10, 1999, issue of the Journal of the American Medical Association suggests that female erectile dysfunction occurs probably at twice the rate of male ED, therefore affecting 30 million women. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition and method for increasing testosterone levels Inventor(s): Yegorova, Inna; (Northridge, CA) Correspondence: Sierra Patent Group, LTD.; P O Box 6149; Stateline; NV; 89449; US Patent Application Number: 20030039701 Date filed: May 2, 2002 Abstract: This invention provides compositions and methods related to the administration of deer antler, one or more nor-testosterone precursors, and one or more testosterone precursors, to increase testosterone levels, treat sexual dysfunction, improve sexual function, improve energy, enhance feelings of well-being and increase muscle mass in males. This invention also provides for inhibitors of the enzymes aromatase and/or 5-alpha reductase, to support testosterone levels and avoid undesirable metabolites. Excerpt(s): This invention relates generally to novel compositions and related methods that combine deer antler, testosterone, testosterone precursors and nor-testosterone precursors, and aromatase and 5-alpha reductase inhibitors in order to increase testosterone levels, treat sexual dysfunction, raise energy levels, improve sexual function, enhance feelings of well-being and increase muscle mass in the human male. Testosterone is the primary androgen or male reproductive (sex) hormone produced naturally in the body. Normal male sexual development, including the sex organs, increases in muscle mass, facial hair, and deep voice, depends on testosterone. In adult males, testosterone effects maintenance of muscle and bone mass, sexual function and psychological well being. As males grow older, however, especially after the age of 35, testosterone levels decline slowly, accompanied by symptoms that have been associated with the condition known as "andropause." Symptoms of andropause include lethargy, depression, lack of sexual desire and function, and loss of muscle mass and strength. Men suffering testosterone deficiency have many replacement therapies available, but each has particular disadvantages. For example, injections of testosterone esters in oil depot form have been used for decades, but these injections are often both inconvenient and painful. Moreover, these injections result in inconsistent testosterone levels in the blood: a supraphysiological surge in testosterone level is seen soon after injection, but by the time of the next injection, testosterone levels have often dropped below standard physiological levels. These supraphysiological surges may increase the incidence of undesirable side effects (e.g.,. prostrate hypertrophy) as well as amplify the shutdown of the hypothalamic/pituitary testicular axis (HPTA). GOODMAN & GILMAN Sec XIII-HORMONES AND HORMONE ANTAGONIST (9.sup.th Ed. 1996). Testosterone is also available as a transdermal system, applied to the scrotal skin, but this causes a disproportionate increase in plasma dihydrotestosterone (DHT) levels due to conversion by the scrotal skin during absorption. GOODMAN & GILMAN (1996).

Patents 171

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods of treatment for conditions responsive to testosterone elevation Inventor(s): Day, Wesley W.; (Old Lyme, CT), Lee, Andrew G.; (Old Lyme, CT), Thompson, David D.; (Gales Ferry, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department,ms 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20010044434 Date filed: January 10, 2001 Abstract: This invention relates to methods and pharmaceutical compositions useful in the treatment of conditions that are responsive to the elevation of testosterone levels in the body and the use of estrogen agonists/antagonists for the manufacture of medicaments for the treatment of conditions that are responsive to the elevation of testosterone levels in the body. The compositions are comprised of an estrogen agonist/antagonist and a pharmaceutically acceptable vehicle, carrier or diluent. These compositions are effective in treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and are effective in increasing libido in female subjects including post-menopausal women. In the case of male subject sexual dysfunction, the compositions may also include a compound which is an elevator of cyclic guanosine 3',5'-monophosphate (cGMP). Additionally, the compositions are effective in other conditions whose etiology is a result of testosterone deficiency or which can be ameliorated by increasing testosterone levels within the body. Methods of the invention include the treatment of conditions that are responsive to elevation of testosterone levels such as treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and the increase of libido of female subjects including post-menopausal women. The methods of treatment are effective while substantially reducing the concomitant liability of adverse effects associated with testosterone administration. Excerpt(s): This application claims priority of U.S. provisional application No. 60/175,704, filed Jan. 12, 2000. This invention relates to compositions and methods for treating conditions responsive to testosterone administration including male subject sexual dysfunction, lowered libido in female subjects including post-menopausal women and timidity in female subjects including post-menopausal women. The compositions and methods utilize estrogen agonist antagonist compounds. Testosterone, the principal androgen, is synthesized in the testis, the ovary, and the adrenal cortex. In the circulation, testosterone serves as a prohormone for the formation of two classes of steroids: 5a-reduced androgens, which act as the intracellular mediators of most androgen action, and estrogens, which enhance some androgenic effects and block others. Thus the net effect of the action of endogenous androgens is the sum of the effects of the secreted hormone (testosterone), its 5a-reduced metabolite (dihydrotestosterone, and its estrogenic derivative (estradiol). Adequate amounts of these hormones are required for proper physical development and physiological homeostasis. When diminished or absent from the body, pathological conditions can arise in the body due to a testosterone deficiency which are treatable by testosterone replacement. Additional conditions can be treated or ameliorated through the supplementation of endogenous testosterone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

172 Testosterone

•

Compositions comprising ethisterone or its derivatives Inventor(s): Carruthers, Malcolm; (London, GB) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20020115648 Date filed: April 8, 2002 Abstract: Treatment of androgen deficiency using a pharmaceutically effective dose of ethisterone or an ethisterone derivative such as danazol. In particular, androgen deficiency in the aging male, also known as the male climateric andropause or the male menopause, can be treated by ethisterone or ethisterone derivatives. Treatment of hypogonadism using ethisterone or ethisterone derivative in combination with testosterone is also effective. Excerpt(s): Androgen Deficiency in the Ageing Male, also referred to as `The Male Climateric`, `The male menopause` and the `Andropause` causes a highly characteristic pattern of symptoms which was first recognised nearly sixty years ago (Werner, A. JAMA 112, 15, 1441-3, 1939). As described at that time, the syndrome includes loss of energy, drive and libido, depression, irritability, joint pains and stiffness, and even such typical symptoms of the female menopause as night sweats and hot flushes. It has been found (Carruthers, M. `The Male Menopause, Harpercollins`, London, 1996) that the symptoms associated with this condition arise due to an absolute or relative insufficiency of testosterone, particularly the latter, caused by a reduction in the Free Active Testosterone (FAT); that is a lack of testosterone present in an unbound state in blood plasma. Testosterone in vivo can be bound to sex hormone binding globulin (SHBG) and to a lesser extent, albumin. When bound the testosterone is not freely available to the body or bio-available. One of the best measures of this is the `Free Androgen Index` (FAI). This is calculated by dividing the Total Testosterone (TT) by the `sex Hormone Binding Globulin` (SHBG) and multiplying by a hundred to express it as a percentage. In the healthy, asymptomatic male this is normally in the range 70-100%. Symptoms of the andropause regularly appear when this drops below 50%, except in a few cases where the TT is low and the body appears to compensate by reducing SHBG levels to maintain the FAI. 2. introducing an agent which competes for the binding sites, thereby displacing bound testosterone which is returned to systemic circulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Compounds and methods for the treatment of urogenital disorders Inventor(s): Grayson, Stephen; (San Rafael, CA), Mak, Vivien H.W.; (Palo Alto, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020198136 Date filed: March 6, 2002 Abstract: The present invention provides methods for treating a variety of urogenital disorders, such as, for example, vaginismus, dyspareunia, vulvodynia (including vulvar vestibulitis), interstitial cystitis, nonspecific urethriris (i.e., nonspecific pain and/or burning of the urinary tract) and sexual dysfunctions, such as, for example, female

Patents 173

sexual arousal disorders and female sexual orgasmic disorders, using a variety of compounds, including, but not limited to, NO donors, calcium channel blockers, cholinergic modulators,.alpha.-adrenergic receptor antagonists,.beta.-adrenergic receptor agonists, phosphodiesterase inhibitors, cAMP-dependent protein kinase activators (e.g., cAMP mimetics), superoxide scavengers, potassium channel activators, estrogen-like compounds, testosterone-like compounds, benzodiazepines, adrenergic nerve inhibitors, antidiarrheal agents, HMG-CoA reductase inhibitors, smooth muscle relaxants, adenosine receptor modulators, adenylyl cyclase activators, endothelin receptor antagonists, bisphosphonates and cGMP-dependent protein kinase activators (e.g., cGMP mimetics). Excerpt(s): The present application claims priority to U.S. Provisional Pat. Application Nos. 60/273,901, filed Mar. 6, 2001, and 60/334,903, filed Oct. 24, 2001, the teachings of both of which are incorporated herein by reference for all purposes. Urogenital disorders affect a large number of women and can have profound effects on life quality. Although a number of treatments are available for some of the most serious gynecological and urinary tract diseases, many urogenital disorders are still poorly understood. As a consequence, treatments are often nonexistent, inefficient and/or invasive. One example of a relatively rare, yet highly debilitating, urogenital disorder is vaginismus. Vaginismus results from the involuntary spasm of the pelvic muscles surrounding the outer third of the vagina, and interferes with a woman's ability to have a sexual relationship. This disorder is a major cause of unconsummated marriage, and can result in marked distress, interpersonal difficulty, and infertility. In addition, women suffering from vaginismus are sometimes unable to undergo a routine gynecological exam. Typical treatments of vaginismus include, for example, psychological therapy, Kegel exercises, and the use of a plastic dilator to progressively stretch the contracted muscles of the vagina. Although often effective, these treatments are time-consuming and cause high levels of anxiety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Delivery of physiologically active compounds through an inhalation route Inventor(s): Rabinowitz, Joshua D.; (Mountain View, CA), Zaffaroni, Alejandro C.; (Atherton, CA) Correspondence: Richard R. Eckman; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030017114 Date filed: May 23, 2002 Abstract: The present invention relates to the delivery of physiologically active compounds through an inhalation route. Specifically, it relates to aerosols containing physiologically active compounds that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of chlordiazepoxide, betahistine, clonidine, testosterone, conjugated estrogens, estrogen esters, estradiol, estradiol esters, ethinyl estradiol, ethinyl estradiol esters, or hyoscyamine. In a method aspect of the present invention, chlordiazepoxide, betahistine, clonidine, testosterone, conjugated estrogens, estrogen esters, estradiol, estradiol esters, ethinyl estradiol, ethinyl estradiol esters, or hyoscyamine is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of chlordiazepoxide, betahistine, clonidine, testosterone, conjugated estrogens, estrogen

174 Testosterone

esters, estradiol, estradiol esters, ethinyl estradiol, ethinyl estradiol esters, or hyoscyamine, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering chlordiazepoxide, betahistine, clonidine, testosterone, conjugated estrogens, estrogen esters, estradiol, estradiol esters, ethinyl estradiol, ethinyl estradiol esters, or hyoscyamine through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of chlordiazepoxide, betahistine, clonidine, testosterone, conjugated estrogens, estrogen esters, estradiol, estradiol esters, ethinyl estradiol, ethinyl estradiol esters, or hyoscyamine; and, b) a device that forms a chlordiazepoxide, betahistine, clonidine, testosterone, conjugated estrogens, estrogen esters, estradiol, estradiol esters, ethinyl estradiol, ethinyl estradiol esters, or hyoscyamine containing aerosol from the composition, for inhalation by the mammal. Excerpt(s): This application claims priority to U.S. provisional application Serial No. 60/294,203 entitled "Thermal Vapor Delivery of Drugs," filed May 24, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. This application further claims priority to U.S. provisional application Serial No. 60/317,479 entitled "Aerosol Drug Delivery," filed Sep. 5, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. The present invention relates to the delivery of physiologically active compounds through an inhalation route. Specifically, it relates to aerosols containing physiologically active compounds that are used in inhalation therapy. It is desirable to provide a new route of administration for physiologically active compounds that rapidly produces peak plasma concentrations of the compound. The provision of such a route is an object of the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

DHEA supplement for increasing women's libido Inventor(s): Thompson, Ronald J.; (Fort Thomas, KY) Correspondence: Donald N. Halgren; 35 Central Street; Manchester; MA; 01944; US Patent Application Number: 20030064123 Date filed: May 30, 2002 Abstract: A method to increase both the libido and sexual responsiveness in a mammalian female. The method comprises the steps of administering a compound having a combination of DHEA, Yohimbe and L-arginine to that female. When a woman's decreased or absent libido, currently referred to in the medical literature as hypoactive sexual desire, is believed in the gynecologic/urologic communities to be caused by a decreased `testosterone effect`, such treatment may be beneficial. This decreased `testosterone effect` can be due to normal aging, contraceptive medications, anti-depressant medication, a lowered cholesterol diet or a decreased percentage of body fat as a result of a rigorous exercise regime. This present invention defines those three above-stated specific nutritional supplements with specific physiological effects well documented in the peer reviewed medical literature. This combination of nutritional supplements increases the testosterone effect in both the brain as well as in the clitoral tissues, to improve a woman's libido, without prescription testosterone preparations, or the uncertainties of non-medically proven herbal remedies. Excerpt(s): This application relates to dietary supplements for women to improve her libido, and more particularly to the use of an oral, daily-dosed nutritional supplement of

Patents 175

DHEA (Dihydroepiandosterone), Yohimbe, and L-Arginine, to increase that woman's libido and sexual responsiveness, and is a continuation-in-part application of my earlier co-pending U.S. patent applications, Ser. No. 09/736,973, filed Dec. 14, 2000, entitled "Clitoral Sensitizing Arrangement" and Ser. No. 09/968,055 filed Oct. 1, 2001, entitled "Treatment of Interstitial Cystitus Using Topical Application of Menthol and L-arginine" both of which are incorporated herein by reference in their entirety. Testosterone significance in women: A woman has one third to one sixth of the serum level of Testosterone as a same aged man in normal situations. A woman's testosterone is produced 25% by her ovaries, and 75% by the adrenal glands and the peripheral fat conversion of DHEA (Dihydroepiandosterone) into androgens. Dr. Kaplan reports that a woman's testosterone level declines `normally` 70% from age 30 to age 60. The medical literature also associates the decline of libido with contraceptive medications, due to the increase in sex-binding globulins in the blood that transports testosterone, antidepressant medications as well as with normal aging. "Potential use of DHEA supplementation for Estrogen and Androgen Replacement in post-menopausal women" "After six months of oral DHEA supplementation (25 mg/day) post-menopausal women's estrogen and testosterone levels returned to premenopausal levels". Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

DOSAGE FORMS AND METHOD FOR AMELIORATING MALE ERECTILE DYSFUNCTION Inventor(s): CLARKE, ANTHONY; (OXFORDSHIRE, GB), GREEN, RICHARD DAVID; (WILTSHIRE, GB), JOHNSON, EDWARD STEWART; (BERKSHIRE, GB) Correspondence: Donald O. Nickey, ESQ.; Cardinal Health; 7000 Cardinal Place; Dublin; OH; 43017 Patent Application Number: 20010018069 Date filed: July 12, 1999 Abstract: The use of a pharmaceutical composition for oral administration comprising a carrier and active ingredient selected from a dopamine agonist, testosterone and mixtures thereof, the composition being in the form of a fast-dispersing dosage form designed to release the active ingredient rapidly in the oral cavity for the manufacture of a medicament for treatment of male erectile dysfunction. Excerpt(s): This invention relates to dosage forms and methods for ameliorating erectile dysfunction in male patients. More particularly, this invention relates to the use of fastdispersing dosage forms of drugs for amelioration of erectile dysfunction in male patients. A normal erection occurs as a result of a coordinated vascular event in the penis. This is usually triggered neurally and consists of vasodilatation and smooth muscle relaxation in the penis and its supplying arterial vessels. Arterial inflow causes enlargement of the substance of the corpora cavernosa. Venous outflow is trapped by this enlargement, permitting sustained high blood pressures in the penis sufficient to cause rigidity. Muscles in the perineum also assist in creating and maintaining penile rigidity. Erection may be induced centrally in the nervous system by sexual thoughts or fantasy, and is usually reinforced locally by reflex mechanisms. Male erectile dysfunction (MED) is defined as the inability to achieve and sustain an erection sufficient for intercourse. In any given case this can result from psychological disturbances (psychogenic), from physiological abnormalities in general (organic), from neurological disturbances (neurogenic), hormonal deficiencies (endocrine) or from a combination of the foregoing.

176 Testosterone

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Elemental nanoparticles of substantially water insoluble materials Inventor(s): Hassan, EmadEldin M.; (Philadelphia, PA) Correspondence: Dann Dorfman Herrell & Skillman; Suite 720; 1601 Market Street; Philadelphia; PA; 19103-2307; US Patent Application Number: 20020119916 Date filed: December 22, 2000 Abstract: This invention relates to a novel process of manufacture of nanoparticles of substantially water insoluble materials from emulsions. The emulsions have the ability to form a single liquid phase upon dilution of the external phase, instantly producing dispersible solid nanoparticles. The formed nanoparticles have average diameter of about 10 to 200 nm and are suitable for drug delivery and targeting of water insoluble therapeutic or diagnostic agents. Examples of such agents are methotrexate, progesterone, testosterone, prednisolone, and ibuprofen. Such agents can be used in a wide range of therapeutic and diagnostic treatments including treatment for cancer, hormonal therapy, and pain management. Excerpt(s): This invention relates to nanoparticles of substantially water insoluble materials, methods of preparation, and use thereof. In particular, the invention relates to nanoparticles of therapeutic and diagnostic agents, method of preparation thereof, and pharmaceutically useful dispersions containing these nanoparticles. This invention further relates to methods of treatment using these nanoparticles. Nanoparticles of substantially water insoluble materials (i.e. materials that have water solubility of less than 0.1%) have a wide variety of applications, including therapeutic and diagnostic agents, paints, inks, dyes, and semiconductors. In most cases, performance of these nanoparticles dramatically improves as the nanoparticle size is reduced to 200 nanometers or less. Nanoparticles of therapeutic and diagnostic agents, in particular of a pharmaceutical compound ("drug") are customarily delivered with a solid or liquid carrier. Liquid containing nanoparticles such as emulsions, microemulsions and liposomes, however, usually suffer from the inherent physical instability of fluids resulting from globule dissociation. Solid polymeric or lipid nanoparticles have more structural stability, yet the rate of biodegradation of the nanoparticles and/or controlled release of the agent in the nanoparticles may not take place as intended, thereby adversely affecting optimal agent delivery and targeting. In addition, only a relatively small amount of the agent or drug can be encapsulated in fluid or solid carriers, requiring large, and sometimes impractical size dosages. Carrier-free nanoparticles, made entirely of a water insoluble therapeutic agent or drug, have been introduced as an alternative solution for the above limitations and drawbacks. There are two major techniques described in the prior art, to produce solid drug nanoparticles. These techniques are known as wet grinding, and antisolvent precipitation. Other general techniques for nanoparticle formation, such as solvent evaporation and emulsion polymerization, are either not suitable or have not proved to be successful in making carrier-free drug nanoparticles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 177

•

Free insulin testosterone test Inventor(s): Lichten, Edward M.; (Southfield, MI) Correspondence: Sonnenschein Nath & Rosenthal; Wacker Drive Station, Sears Tower; P.O. Box 061080; Chicago; IL; 60606-1080; US Patent Application Number: 20020061869 Date filed: July 2, 2001 Abstract: The present invention is directed to a method of identifying a mammal with a hormone disorder, or identifying a mammal at risk of developing a hormone disorder. The method comprises determining the serum concentration of estrogen, testosterone, sex hormone-binding globulin, and insulin in the mammal, calculating their ratio, or F factor, and administering to the mammal a hormone disorder-effective amount of a therapeutic agent until a therapeutic F factor is achieved, or maintained in the mammal. The present invention is also directed to methods, kits, combinations, and compositions for treating, preventing or reducing the risk of developing a hormone disorder, or a disease or disorder associated with, or related to, a hormone disorder, such as cardiovascular disease. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 09/198,798, entitled, "Use of Testosterone to Treat Impaired Glucose Tolerance and Insulin Resistance and Method of Screening for Insulin Resistance in Adult Onset Diabetes and Syndrome X," filed Nov. 24 1998, the disclosure of which is expressly incorporated by reference. The present invention relates to a method of identifying a mammal with a hormone disorder, or a mammal at risk of developing a hormone disorder; and to methods, kits, combinations, and compositions for treating a mammal with a hormone disorder or a mammal at risk for developing a hormone disorder, or a disease or disorder associated with, or related to, a hormone disorder. The cause and manifestation of cardiovascular disease is multifactorial. Many studies have sought to discover a common hormonal denominator to explain the predominance of coronary arterial disease in men. There is agreement among many authors that the presence of hypotestosteronemia (low testosterone) (Phillips et al., 1994), hypoadrenalism (low dehydroepiandrosterone sulfate) (Nafziger et al., 1991; Mitchell et al., 1994; and Newcomer et al., 1994) and/or increased sex hormone-binding globulin (Phillips et al., 1994) defines a state for men for increased risk of coronary artery disease and myocardial infarction. However, there is no such consensus for women. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

HAIR LOSS PREVENTION Inventor(s): Knowles, W. Roy; (Houston, TX) Correspondence: Mark Pohl; 55 Madison Avenue; 4th Floor; Morristown; NJ; 07960 Patent Application Number: 20020086873 Date filed: January 11, 2002 Abstract: Compositions to prevent or reduce hair loss, allowing the body to maintain normal, healthy hair growth, comprising a penetration enhancer together with a testosterone blocker or a vascular enhancer, or both. Excerpt(s): My invention relates to preparations useful for maintaining normal, healthy hair bulb function, for preventing hair loss, and for medically treating androgenic

178 Testosterone

alopecia and like dermatological diseases. I will first review pertinent hair biology, then discuss prior art teachings in the field, and then describe my invention. Hair Biology Hair bulbs are responsible for normal, healthy hair growth and retention. Hair bulbs are located in the skin, about {fraction (3/16)} of an inch below the skin surface. They are located just above the fatty layer at the very lower most position of the skin. The majority of facial and body hair growth is stimulated by androgens. However, the growth of scalp hair has been shown, in genetically programmed individuals, to be inhibited by 5.alpha.-dihydrotestosterone ("DHT") in individuals who exhibit a hereditary pre-disposition to baldness. Ebling, Dermatol. Clin. S. 467 (1987); Lucky, 4 Biochem. Soc. Transc. 597 (1988); Brodland et al., 47 Cutis 173 (1991). DHT is produced by reducing testosterone with a 5.alpha.-reductase enzyme. The phenotypic expression of baldness does not occur in the absence of testosterone. Androgenic alopecia or common baldness represents 99 percent of all cases of hair loss. Broadland, id. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Hormone therapy methods and hormone products for abating coronary artery blockage Inventor(s): Chein, Edmund Y.M.; (Palm Springs, CA) Correspondence: Patrick F. Lorig, P.C.; Bright & Lorig, P.C.; 633 West Fifth Street, Suite 3330; Los Angeles; CA; 90071; US Patent Application Number: 20020065273 Date filed: February 5, 2000 Abstract: Methods for abating coronary artery blockage in human subjects include administering a combination of natural hormones including human growth hormone with sufficient T3 thyroid supplement to maintain the body temperature of the subject at or above 97.6.degree. F. upon awakening and at 98.7.degree. F. or higher during afternoon hours. Testosterone, if any, administered to male subjects is in natural, gel form. Excerpt(s): This invention relates to methods and products to abate coronary artery blockage in men and in women. These methods include administering a combination of natural hormones, including human growth hormone or recombinant human growth hormone, one or more sex hormones, such as testosterone, estrogen or progesterone and other naturally occurring hormones, as appropriate. The methods and products of this invention are disclosed in part in U.S. Pat. No. 5,855,920, issued Jan. 5, 1999, entitled TOTAL HORMONE REPLACEMENT THERAPY. The entire text of the '920 patent is incorporated herein by this reference. However, in abating coronary artery blockage in men and women, the methods of this invention additionally call for administering sufficient T3 thyroid supplement to maintain the body temperature of males and females with such blockage above about 97.6.degree. F. upon awakening, and is in the range of about 98.7.degree. F. to about 99.0.degree. F. during the afternoon hours. In addition, in treating males with coronary artery blockage, and with below optimal testosterone levels, these methods call for administering natural testosterone in gel form, preferably applied topically to under arm pits. In treating a human male or female subject who has blockage of coronary arteries, a treating physician preferably obtains the subject's records, including, where available, MRI, CAT scan, angiogram and all other pictorial and visual documentation of the blockage. The treating physician then measures the subject's total cholesterol, HDL, LDL, and triglyceride levels, and the subject's hormones in terms of growth hormone level as reflected through IGF-1 level,

Patents 179

melatonin level, thyroid hormone level, thymus hormone level, adrenal hormone of DHEA level and pregnenolone level, and the subject's sex hormone(s) level (in males, testosterone; in females, progesterone and estrogen). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Increasing libido in humans via acute testosterone administration Inventor(s): Cole, Robert; (Alamo, CA), Rubsamen, Reid M.; (Alamo, CA) Correspondence: Karl Bozicevic; Bozicevic, Field & Francis Llp; Suite 200; 200 Middlefield Road; Menlo Park; CA; 94025; US Patent Application Number: 20020002973 Date filed: March 19, 2001 Abstract: The libido of adult human female patients is increased by the bolus delivery of a testosterone which is preferably dihydrotestosterone. The formulation is preferably aerosolized and inhaled into a patient's lungs where particles of testosterone deposits on lung tissue and then enter the patient's circulatory system. The patient's testosterone level is quickly enhanced well above baseline levels for a short period and subsides to baseline levels with normal metabolism thereby providing desired short term effects on enhanced libido without undesirable effects of long term enhanced testosterone levels. Additional formulations are provided including formulations for aerosolized delivery of sildenafil citrate which are delivered to male or female patients. Excerpt(s): This application claims priority to, and incorporates by reference in its entirety, earlier filed U.S. application Ser. No. 09/563,773 filed May 2, 2000 and provisional patent application 60/132,472 filed May 4, 1999. This invention relates generally to a method of treating humans with a decreased libido. More specifically, the invention relates to acute, bolus non-invasive administration of testosterone to enhance libido over a discrete period of time. The presence of a normal amount of libido, defined as the urge to engage in sexual activity, is an important component of an individual's well-being. In both men and women the primary naturally occurring hormone responsible for libido is testosterone. In males, the baseline testosterone level is a relatively constant throughout life, decreasing slowly in old age. In contrast, women elaborate testosterone only as part of the process of ovulation. Each maturing follicle produces testosterone at the mid-point of the menstrual cycle, consistent with observations that female libido peaks with ovulation. As a woman ages, the number of maturing follicles per month decreases, and there is a decreasing total amount of testosterone produced. A common complaint of post menopausal women is decreased libido. This decrease in libido is characterized by a lack of interest in sexual intercourse, the lack of ability to achieve orgasm, or decrease in intensity of orgasm. It is important to note that this decrease in libido is often associated with a profound sense of loss of a once normal and active interest in sexual activity. Low levels of testosterone in, e.g., hypogonadal men are associated with lack of libido and absence of erections. They respond to therapy with exogenous testosterone (Cunningham et al., J Clin Endocrinol Metab, (March 1990) 70:792-7; Behre et al., J Clin Endocrinol Metab, (November 1992) 75:1204-10; and women also respond to testosterone therapy, see Tuiten et al., Arch. Gen. Phychiatry, (February 2000) 57:149-153. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

180 Testosterone

•

Male contraceptive formulation comprising norethisterone Inventor(s): Kamischke, Axel; (Muenster, DE), Nieschlag, Eberhard; (Muenster, DE), Oettel, Michael; (Jena, DE), Ruebig, Alexander; (Berlin, DE), Schillinger, Ekkerhard; (Berlin, DE), Ursula-Friederike, Habenicht; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020103176 Date filed: January 19, 2001 Abstract: A formulation for male contraception comprising a progestin possessing both estrogenic and androgenic properties is remarkably effective for spermatogenesis suppression in males. The progestin Norethisterone (NET), particularly its derivatives Norethisterone acetate and Norethisterone enanthate in sufficient doses induce oligozoospermia or azoospermia in males. Formulations further comprising an androgen, such as a testosterone derivative such as a testosterone ester, particularly testosterone undecanoate, are especially effective male contraceptive formulations. Excerpt(s): The invention relates to a formulation of a male contraceptive comprising a progestin as well as methods of male contraception utilising progestins. Moreover, the invention relates to formulation further comprising an androgen as well as to methods using formulations comprising a progestin and an androgen so as to suppress spermatogenesis. Contraceptive methods for men are considered an essential component of world-wide reproductive health (Nieschlag and Behre; Testosterone: action, deficiency, substitution, 1998, Springer, Berlin, p 514). Hormonal methods of male contraception offer the advantages of high-reversibility and efficacy. In hormonal male contraception, the suppression of spermatogenesis is sought through the suppression of the gonadotropins leuteinizing hormone (LH) and follicle stimulating hormone (FSH) to undetectable levels within the endocrine feedback mechanism operating between the pituitary gland and the hypothalamus. Disadvantageously, suppression of these gonadotropins also induces symptoms related to androgen deficiency (Nieschlag and Behre; 1998, pp 513-528). Male contraceptive methods seek to suppress FSH and LH, resulting in a depletion of intratesticular testosterone and cessation of spermatogenesis, whilst substituting peripheral testosterone with another androgen. This androgen has typically been testosterone itself and serves the endocrine androgenic role of testosterone such as to maintain libido, male sex characteristics, protein anabolism, hematopoesis and others. In short, the objective is to deplete the testes of testosterone whilst maintaining levels in the general circulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Medicinal preparations for treating sex hormone-dependent diseases Inventor(s): Igari, Yasutaka; (Hyogo, JP), Kamei, Shigeru; (Hyogo, JP) Correspondence: Takeda Pharmaceuticals North America, Inc; Intellectual Property Department; 475 Half Day Road; Suite 500; Lincolnshire; IL; 60069; US Patent Application Number: 20030176360 Date filed: January 2, 2003 Abstract: Medicinal preparations for treating sex hormone-dependent diseases which comprise a combination of a compound having a luteinizing hormone-releasing

Patents 181

hormone agonistic effect or its salt with a compound having a luteinizing hormonereleasing hormone antagonistic effect or its salt for administering the compound having a luteinizing hormone-releasing hormone agonistic effect or its salt followed by the compound having a luteinizing hormone-releasing hormone antagonistic effect or its salt. By using these preparations, the concentration of a sex hormone (for example, testosterone, LH, FSH, estrogen) can be quickly recovered after the medicable period of a compound having a luteinizing hormone-releasing hormone antagonistic effect or its salt or a preparation containing the same (preferably a sustained-release preparation), which makes it possible to definitely determine the drug cessation period in an intermittent treatment. Excerpt(s): The present invention relates to (1) a medicinal preparation for treating sex hormone-dependent diseases comprising a combination of a compound having a luteinizing hormone-releasing hormone agonistic effect or a salt thereof with a compound having a luteinizing hormone-releasing hormone antagonistic effect or a salt thereof, for administering the compound having a luteinizing hormone-releasing hormone agonistic effect or a salt thereof followed by the compound having a luteinizing hormone-releasing hormone antagonistic effect or a salt thereof, (2) a method for using a compound having a luteinizing hormone-releasing hormone agonistic effect or a salt thereof and/or a compound having a luteinizing hormone-releasing hormone antagonistic effect or a salt thereof for the preparation of a pharmaceutical composition for treating sex hormone-dependent diseases, said composition being characterized by administering the compound having a luteinizing hormone-releasing hormone agonistic effect or a salt thereof followed by the compound having a luteinizing hormonereleasing hormone antagonistic effect or a salt thereof, and the like. A luteinizing hormone-releasing hormone which is known as LHRH (or GnRH) is released from hypothalamus and binds to a receptor of glandula pituitaria. LH (luteinizing hormone) and FSH (follicle stimulating hormone) which are released due to this act on gonadal gland to synthesize a steroid sex hormone. The successive administration of a compound having a potent luteinizing hormone-releasing hormone agonistic effect results in the reduction of the number of the available receptor and the formation of a steroid sex hormone derived from gonadal gland is suppressed. By utilizing this, a compound having a luteinizing hormone-releasing hormone agonistic effect is clinically applied as medicaments for treatment of sex hormone-dependent diseases such as prostate cancer, benign prostatic hyperplasia, endometriosis, hysteromyoma, metrofibroma, precocious puberty, breast cancer, and the like. As a treatment method comprising preventing and delaying the change of sex hormone-dependent diseases (especially prostate cancer) into sex hormone-independent, an intermittent treatment comprising administration cessation of a compound having a luteinizing hormonereleasing hormone agonistic effect for a drug starving, and exposing to a sex hormone with a sufficient concentration so as to maintain the disease being hormone-dependent in a treatable state, is used (for example, Cancer, 71(1993) 2782-2790). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

182 Testosterone

•

Method and compositions for regulation of 5-alpha reductase activity Inventor(s): Hiipakka, Richard; (Chicago, IL), Liao, Shutsung; (Chicago, IL) Correspondence: Joseph Mahoney; Mayer, Brown, Rowe & Maw; P.O. Box 2828; Chicago; IL; 60690-2828; US Patent Application Number: 20030105030 Date filed: April 24, 2002 Abstract: Pharmaceutical compositions and methods for treating androgen related disorders. The pharmaceutical compositions may include a 5.alpha.-reductase inhibitor, such as natural and synthetic flavanoids, catechols, curcumin-related substances, quinones, catechins, particularly epigallocatechin derivatives, fatty acids, and the salts, esters, analogues, pro-drugs, isomers, racemic mixtures, or derivatives of any of the foregoing. The use of testosterone (or DHT) combinations with the aforementioned 5.alpha.-reductase inhibitor compounds is also contemplated. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/530,443, filed on Apr. 28, 2000, which claims priority to International Application No. PCT/US98/23041, filed on Oct. 30, 1998, which claims priority to U.S. Provisional Application Ser. No. 60/063,770, filed on Oct. 31, 1997. This application claims priority to all such previous applications, and such applications are hereby incorporated herein by reference. The present invention relates generally to compounds, compositions and methods regulating the action and function of androgens and other steroid hormones by modulating the activity of steroid-reductases, including isozymes of.alpha.-reductases. In some of the androgen-sensitive organs, such as the prostate and skin, testosterone (T) is converted to a more active metabolite 5.alpha.-dihydrotestosterone (DHT) by 5.alpha.reductase (Anderson and Liao, 1968; Bruchovsky and Wilson, 1968). Other substrates of 5.alpha.-reductases are also converted to reduce products that may have specific properties. Inhibition of 5.alpha.-reductase represents a unique approach for developing therapeutic methods for androgen-dependent diseases, such as benign prostatic hyperplasia, breast and prostatic cancer, skin disorders, seborrhea, common baldness, hirsutism, and hidradenitis suppurative. Various compounds have been shown to inhibit 5.alpha.-reductase activity (Liang and Liao, 1992; Hirsch et al., 1993; Russell and Wilson, 1994; Liao and Hiipakka, 1995). Finasteride (Proscar), a 5.alpha.-reductase inhibitor, lowers the level of DHT in serum and the prostate, reduces prostate volume and increases urinary flow in some patients (Stoner E. Finasteride Study Group, 1992). Certain aliphatic unsaturated fatty acids, such as.gamma.-linolenic acid (Liang and Liao, 1992) and catechin-3-gallates (Liao and Hiipakka, 1995), can inhibit 5.alpha.-reductase activity of liver and prostate of rats and humans in vitro. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Method and compositions for the treatment or amelioration of female sexual dysfunction Inventor(s): Adams, Michael A.; (Kingston, CA), Heaton, Jeremy P. W.; (Gananoque, CA) Correspondence: Parteq Innovations; Queen's University; Room 1625; Biosciences Complex; Kingston; ON; K7l 3n6; CA Patent Application Number: 20020193442 Date filed: April 22, 2002

Patents 183

Abstract: The present invention provide a method of treating sexual dysfunction in a female, including the vasculogenic symptoms of delayed vaginal engorgement, diminished vaginal lubrication, pain or discomfort with intercourse (dyspareunia), diminished vaginal sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished clitoral orgasm, or of combating vaginal pain by stimulating peripheral pelvic nerve release of nitric oxide (NO). The method comprises administering to a female in need of such treatment a therapeutically effective amount of a compound which acts on a mid-brain pathway to increase blood flow to the ilio-hypogastricpudendal artery bed and stimulate the release of nitric oxide (NO) from peripheral NANC nerve cells. The preferred compound for the method of this invention is apomorphine or one of its pharmaceutically acceptable salts, esters, or pro-drugs. Alternatively, the apomorphine is co-administered with an apomorphine-potentiating amount of an androgen, preferably testosterone either prior to, or concomitantly with, the administration of the apomorphine. Excerpt(s): This application is a continuation-in-part of co-pending application, Ser. No. 09/102,987 filed Jun. 22, 1998 which is a continuation-in-part of application Ser. No. 08/546,498 filed Oct. 20, 1995, now U.S. Pat. No. 5,770,606 which, in turn, is a continuation-in-part of application Ser. No. 08/231,250 filed on Apr. 22, 1994, now abandoned. The present invention relates to methods of diagnosing, treating, or ameliorating sexual dysfunction in female mammals, including methods of treating delayed vaginal engorgement, diminished vaginal lubrication, pain or discomfort with intercourse (dyspareunia), diminished vaginal sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished clitoral orgasm, or of treating vaginal pain by stimulating peripheral pelvic nerve release of nitric oxide (NO). The treatment methods of the present invention include the improvement in a female of the physiological state associated with sexual activity including appropriate vaginal lubrication, vaginal sensation, vaginal orgasm, or clitoral sensation, but in whom one of the above-mentioned abnormal conditions may not be present. Sexual response in mammals is mediated by a balanced interplay between the sympathetic and parasympathetic nervous systems. Vasocongestion, or erectile tumescence in both the male and female, is largely mediated by parasympathetic (cholinergic) outflow, whereas orgasm is predominantly sympathetic (adrenergic). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of increasing testosterone and related steroid concentrations in women Inventor(s): Dudley, Robert E.; (Kenilworth, IL) Correspondence: Thomas R. Stiebel, JR.; Mayer, Brown, Rowe & Maw; P.O. Box 2828; Chicago; IL; 60690; US Patent Application Number: 20030022877 Date filed: May 21, 2002 Abstract: The present invention relates to methods, kits, combinations, and compositions for treating, preventing or reducing the risk of developing a testosterone deficient disorder, or the symptoms associated with, or related to a testosterone deficient disorder in a subject in need thereof. The present invention also relates to a method of administering a steroid in the testosterone synthetic pathway to a subject in need thereof. In addition, the methods, kits, combinations and compositions may be used in conjunction with other pharmaceutical agents effective at treating, preventing, or reducing the risk of developing a testosterone deficient disorder. The present

184 Testosterone

invention also can also be used in conjunction with a pharmacologically effective amount of an estrogenic hormone. Furthermore, the methods, kits, combinations and compositions can be used in conjunction with a pharmacologically effective amount of another steroid or pharmaceutical agent that increases serum testosterone levels in a mammal. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/292,398, filed May 21, 2001, which is hereby incorporated by reference. The present invention is related to methods, kits, combinations, and compositions for transdermally delivering an effective amount of testosterone to a subject in need thereof. Transdermal preparations of testosterone have provided a useful delivery system for normalizing serum testosterone levels in hypogonadal men and preventing the clinical symptoms and long term effects of androgen deficient men. Available transdermal preparations of testosterone include, for example, TESTODERM.RTM., TESTODERM.RTM. TTS, and ANDRODERM.RTM. Testosterone is also available in other formulations including those available as an injectable, for example, DEPO-TESTOSTERONE.RTM. (testosterone cypionate), and DELATESTRYL BTG.RTM. (testosterone enanthate), or as a gel, for example, ANDROGEL.RTM. marketed by Unimed Pharmaceuticals, Inc., Deerfield, Ill., the assignee of this application. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method to use transdermal administration of androgens to the adnexa of the eye Inventor(s): Connor, Charles Gerald; (Germantown, TN) Correspondence: Butler, Snow, O'mara, Stevens & Cannada Pllc; 6075 Poplar Avenue; Suite 500; Memphis; TN; 38119; US Patent Application Number: 20030144635 Date filed: January 30, 2002 Abstract: This invention relates to a method for treating dry eye or increasing contact lens wear time through the transdermal delivery of androgenic hormones to the adnexa of the eye. More specifically, an androgenic hormone such as testosterone or dehydroepiandrosterone is solubilized in pharmaceutically effective carrier such as a facial cream or gel. The androgenic hormone in a pharmaceutically effective carrier is applied to the adnexa of the eye, which is the tissue adjacent to and surrounding the eyeball. Excerpt(s): NONE. NOT APPLICABLE. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Methods and compositions for treating diseases due to androgen deficiency with glucocorticoid receptor antagonist compounds and new compounds Inventor(s): Patchev, Vladimir; (Jena, DE), Schubert, Gerd; (Jena, DE), Sobek, Lothar; (Jena, DE) Correspondence: Striker, Striker & Stenby; 103 East Neck Road; Huntington; NY; 11743; US Patent Application Number: 20030064973 Date filed: August 13, 2002

Patents 185

Abstract: The method of treating or preventing a disease in a human male or a male animal caused by a decreased production of androgens, such as testosterone, in the human male or male animal includes administering an effective amount of a glucocorticoid receptor antagonist to the human male or the male animal in order to increase production of the androgens. These diseases include male sexual dysfunction, infertility and hypogonadism. Novel androgen receptor antagonist compounds and methods of synthesis are also described. Excerpt(s): The subject matter disclosed herein is at least partially the same as the subject matter disclosed in U.S. Provisional Application, Ser. No. 60/315,099, filed Aug. 27, 2001. The invention relates to the use of glucocorticoid receptor antagonists for the prevention and treatment of diseases of the male reproductive system, as well as to glucocorticoid receptor antagonists, which are particularly suitable for this purpose. It is well known that physical and/or mental stress, age as well as exogenous factors, such as drugs and excessive consumption of alcohol, can lead to sexual dysfunctions and hypogonadism in men. According to presently existing understanding, these diseases are caused by a decreased androgen production, especially by a decreased testosterone production. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treating androgen deficiency in men using selective antiestrogens Inventor(s): Fisch, Harry; (Scarsdale, NY) Correspondence: Clifford Chance Rogers & Wells Llp; 200 Park Avenue; New York; NY; 10166-0153; US Patent Application Number: 20020120012 Date filed: February 21, 2002 Abstract: The administration of antiestrogens to men suffering a relative androgen deficiency stimulates the body's production of testosterone leading to a correction of the deficiency. For example, male menopause, loss of cognitive function, insulin resistance, type 2 diabetes, obesity, excessive weight, Alzheimer's disease, and combinations thereof, can all be characterized by significant decreases in serum levels of bioavailable androgens. Administration of antiestrogens to men restores optimum serum levels of bioavailable androgens, and, thus, serves as a treatment for these disorders and relative androgen deficiency in general. Excerpt(s): This application is a continuation-in-part application of application Ser. No. 09/980,652 filed Oct. 26, 2001 which claims the priority of PCT/US01/15900 filed May 15, 2001 and which claims priority from application S.No. 60/207,496 filed May 26, 2000. The invention relates to the new use of antiestrogens for the production of a pharmaceutical agent for treating a relative androgen deficiency in men. In men, increasing age leads to a reduction of testicular androgen production and androgen concentration in the organism. In contrast to the situation in women, in whom estrogen production drops to castration values within a comparatively short period, this takes decades in men and involves a gradual drop. The total concentration of testosterone in the serum in the older age group is significantly reduced compared to the values in young men. Because of the increase in steroid hormone-binding globulin (SHBG) that coincides with the aging process, moreover, the proportion of free, unbound, and thus biologically active testosterone drops. In addition, the serum levels of estrogens, although they are produced from androgens by direct conversion, do not drop in the

186 Testosterone

same way as a function of age. As a result, the hormonal environment is significantly altered. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treating cognitive decline disease conditions with androgens Inventor(s): Mucke, Lennart; (San Francisco, CA), Raber, Jacob; (Portland, OR) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030139362 Date filed: September 27, 2002 Abstract: Methods for treating a host, particularly a female host, for a cognitive decline disease condition are provided. Also provided are methods for improving the cognitive function of a host. In the subject methods, an effective amount of androgenic agent, e.g., a male sex hormone such as testosterone or analogue thereof, is administered to the host, resulting in at least an improvement in cognitive function of the host. The subject methods find use in a variety of different applications, and are particularly suited for use in treating female hosts for neurodegenerative disease conditions, e.g., Alzheimer's disease. Also provided are kits for use in practicing the subject methods. Excerpt(s): This application is a continuation-in-part of International Patent Application No. PCT/US01/10448, filed Mar. 29, 2001, which is incorporated herein by reference in its entirety and to which application we claim priority under 35 USC.sctn. 120, and claims the benefit of U.S. Provisional Patent Application No. 60/193,005, filed Mar. 29, 2000, which application is incorporated herein by reference in its entirety. The field of this invention is cognition and methods for enhancing cognitive function, e.g., for treatment of cognitive decline disease conditions, such as neurodegenerative disease conditions. Alzheimer's Disease (AD) is a progressive, neurodegenerative disease characterized by cognitive and non-cognitive behavioral changes which include: (a) memory loss; (b) language deterioration; (c) impaired visuo-spatial skills; (d) poor judgment; (e) indifferent attitude and (f) aimless, unpredictable behavior. Although AD usually begins after age 60, its onset may occur decades earlier. AD first appears as memory decline. As the disease progresses over several years, cognition, personality, and the ability to function are all impaired or destroyed. Confusion, anxiety, disruption of circadian rhythm, and restlessness may also occur. The type, severity, sequence, and progression of mental changes vary widely among AD patients. Some people have the disease for only the last 5 years of life, while others may have it for as many as 20 years. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Novel 17-azolyl steroids useful as androgen synthesis inhibitors Inventor(s): Brodie, Angela; (Fulton, MD), Njar, Vincent C.O.; (Baltimore, MD) Correspondence: Sughrue, Mion, Zinn, Macpeak & Seas, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037-3213; US Patent Application Number: 20010001099 Date filed: December 29, 2000

Patents 187

Abstract: Androgen synthesis inhibitors, as well as methods for the use of the same to reduce plasma levels of testosterone and/or dyhydrotestosterone, and to treat prostate cancer and benign prostatic hypertrophy, are disclosed. Excerpt(s): 1. The development of the present invention was supported by the University of Maryland, Baltimore, Md. 2. The present invention relates to novel 17azolyl steroids which are useful as androgen synthesis inhibitors, as well as methods for the use of the same to reduce plasma levels of testosterone and/or dyhydrotestosterone, and to treat prostate cancer and benign prostatic hypertrophy. 3. Breast cancer kills 45,000 women per year. In addition, prostate cancer now ranks as the most prevalent cancer in men. Approximately 160,000 new cases are diagnosed with prostate cancer each year. Of these, 35,000 will die of metastatic disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

NUTRITIONAL SUPPLEMENT COMPRISING AT LEAST ONE PROHORMONE AND AT LEAST ONE ANTI-ESTROGEN COMPOUND IN A TIME-RELEASE DOSAGE FORM Inventor(s): WILDING, BRIAN J.; (WINNIPEG, CA) Correspondence: Standley & Gilcrest Llp; 495 Metro Place South; Suite 210; Dublin; OH; 43017; US Patent Application Number: 20010008638 Date filed: July 14, 1999 Abstract: The present invention relates to an oral dosage delivery form which is effective in increasing the testosterone levels in humans. In a preferred embodiment, the composition comprises a mixture of four (4) prohormones, three (3) anti-estrogen agents and at least one (1) enteric coating. The inventive prohormone/anti-estrogen timerelease dosage form allows the prohormone/anti-estrogen ingredients to be released over an extended period of time so as to provide for a sustained elevated blood serum testosterone level. Excerpt(s): This invention relates to a nutritional supplement that comprises at least one (1) anabolic compound, such as 4-androstene-3.beta., 17.beta. diol and at least one (1) anti-estrogen compound, such as saw palmetto extract, in a time-release dosage form that, for example, comprises at least one (1) enteric coating, more preferably at least two (2) enteric coatings. The steroid hormone testosterone is considered to be the male virility hormone. Its effects include maintenance of muscle and bone mass, sexual function and physiological well being. After about the age of 35, the typical human male experiences a slow decline in testosterone levels. This decline in testosterone levels results in depression, lethargy, lack of sexual desire and loss of muscle mass and strength. Testosterone injections, in oil depot form, have been used to counteract the decline in testosterone levels, however, these injections are inconvenient, often painful and result in inconsistent blood levels. Typically, a supraphysiological surge is seen immediately after the injection, but by the time the next injection is due, the levels have often dropped below their standard physiological level. This is in contrast to the typical cycle of testosterone in human males which pulses about every 90 minutes. The extremely high blood serum levels of testosterone found after depot injections may cause prostrate hypertrophy as well as the potential shutdown of the hypothalamic/pituitary testicular axis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

188 Testosterone

•

Oral fast-dissolving compositions for dopamine agonists Inventor(s): Clarke, Anthony; (Henley-on-Thames, GB), Green, Richard David; (Marlborough, GB), Johnson, Edward Stewart; (Ruscombe, GB) Correspondence: Donald O. Nickey; Cardinal Health, INC.; 7000 Cardinal Place; Dublin; OH; 43017; US Patent Application Number: 20020156056 Date filed: December 24, 2001 Abstract: The present invention discloses the use of a pharmaceutical composition for oral administration comprising a carrier and active ingredient selected from a dopamine agonist, testosterone and mixtures thereof, the composition being in the form of a fastdispersing dosage form designed to release the active ingredient rapidly in the oral cavity for the manufacture of a medicament for treatment of male erectile dysfunction. Excerpt(s): This invention relates to pharmaceutical compositions, a process for preparing such compositions, the use of such compositions for the treatment and/or evaluation of Parkinson's disease and products and kits for the administration of a dopamine agonist and the co-administration of a dopamine agonist and an anti-emetic and/or opioid antagonist. Parkinson's disease is a progressive neurodegenerative disorder caused by a loss of the cell bodies of dopaminergic neurons from the substantia nigra and degeneration of nerve terminals in the striatum resulting in low levels of dopamine in the substantia nigra and corpus striatum. Parkinson's disease is characterised by chronic, progressive motor dysfunction and its main symptoms are tremor at rest, muscle rigidity and a decrease in the frequency of voluntary movements (hypokinesia) with difficulty in stopping, starting and turning when walking. A persistent tremor is superimposed on hypertonicity of opposing muscle groups and initiation of-movements becomes increasingly difficult and slow. In advanced stages, patients' movements become virtually "frozen" and patients are unable to care for themselves. Studies have shown that the symptoms of Parkinson's disease appear when the striatal dopamine content is reduced to 20-40% of normal. As Parkinson's disease is associated with a loss of dopamine from the striatum, it is commonly treated with drugs which replace dopamine, the most commonly used of these being levodopa. Levodopa is converted by dopa decarboxylase into dopamine in the brain and it is this dopamine which exerts a therapeutic effect. However, although levodopa is well absorbed from the small intestine, much of it is inactivated by monoamine oxidase in the wall of the intestine. Also, the plasma half-life of levodopa is short and about 95% of the drug is converted to dopamine in peripheral tissues, where dopa decarboxylase is widespread, with the result that less than 1% enters the brain. Consequently levodopa has to be administered in large and frequent doses. in addition, the production of dopamine in peripheral tissues gives rise to unwanted side effects. Accordingly, levodopa is normally given in combination with other drugs to enhance the effects of levodopa in the brain and minimise its peripheral effects. In particular, levodopa is usually given in combination with a peripheral dopa-decarboxylase inhibitor which cannot cross the blood-brain barrier, such as carbidopa, which inhibits the breakdown of levodopa to dopamine outside the brain, thereby reducing peripheral unwanted effects. The inhibitor also ensures that a relatively large amount of an oral dose of levodopa reaches the brain and thus enables the dose of levodopa to be reduced which also reduces peripheral side effects. In addition, a peripheral dopamine antagonist which does not

Patents 189

penetrate the blood-brain barrier, such as domperidone, may also be administered to reduce the nausea and vomiting side-effects of levodopa. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Rhodiola and uses thereof Inventor(s): Xiu, Rulin; (Washington, DC) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020127285 Date filed: May 7, 2002 Abstract: The present invention relates to Rhodiola, preferably Rhodiola crenulata, to treat various conditions and diseases in mammals. Rhodiola crenulata is a Tibetan herb which has been discovered to have highly useful and beneficial properties heretofore unknown. Rhodiola crenulata is especially preferred to enhance blood oxygen levels, to enhance working capacity and endurance, to enhance memory and concentration, to enhance cardiac and cardiovascular function, to provide antioxidant effects, to protect against oxidation, to modulate testosterone and estradiol levels, to modulate sleep, and to enhance sexuability, such as improve sexual performance. Excerpt(s): The present invention relates to compositions, articles of manufacture, extracts, compounds, methods of use, methods of treatment, methods of preparation, etc., which relate to plants of the genus Rhodiola, preferably Rhodiola crenulata, which have a variety of useful and beneficial effects, including, e.g., to enhance blood oxygen and nutrients levels, e.g., through enhancing oxygen transport, to enhance working capacity and endurance, to reduce muscle fatigue, to enhance memory and concentration, to reduce stress, to enhance cardiac and cardiovascular function, to provide antioxidant effects, to protect against oxidation, to provide anti-cancer effects, to promote DNA repair, to provide anti-radiation effects, to protect against radiation, to reduce inflammation, to increase insulin, to decrease levels of glucagon, to reduce histamine release, to reduce allergic reactions, preferably, to modulate testosterone levels, and to modulate sleep, especially to promote sleep, to modulate blood lipids, preferably, e.g., to lower cholesterol levels, to promote weight loss, and to enhance sexuability, such as improve sexual performance. Rhodiola crenulata is a species of Rhodiola which grows mostly in Tibet and south west of China on the altitude between 3400 meters to 5600 meters. It has been used in Tibetan medicine for more than 1000 years for uses that have been limited to curing lung inflammation and cough, for stopping and activating blood, and for treating external wounds and burns. It has been discovered herein that Rhodiola crenulata has other beneficial properties that make it useful for a variety of conditions and diseases, as mentioned above and below. Rhodiola is a diverse genus of plants which includes more than 50 different species, including, e.g., algida, arctica, crenulata, elongata, gelida, imbricataishidae, iremelica, kirilowii, linearifolia, phariensis, pinnatifida, quadrifida, aff. quadrifida, rosea, sachalinensis, and wolongensis. These species vary from each other widely, differing in, e.g., chromosome number (e.g., Makoto et al., Journal of Japanese Botany, 70(6):334-338, 1995), chemical composition, morphology, medicinal properties, developmental stages (e.g., Ishmuratatova and Satsyperova, Rastitel'nye Resursy., 34(1):3-11, 1998), geographical distribution, etc. Scientific studies (e.g. Peng et al, Chinese Herb Medicine(1995), 26(4): 177-179, and Wang et al, Acta Phrmaceutica Sinica(1992), 27(2): 117-120) indicate constituents of Rhodiola crenulata include, e.g., salidroside, tyrosol,.beta.-sitosterol,

190 Testosterone

gallic acid, pyrogallol, crenulatin, rhodionin, rhodiosin, among which, crenulatin, e.g., is found only in R. crenulata and has not been found in any other Rhodiola species. Rhodiosin and rhodionin exists in some, but not all, Rhodiola species. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Selective androgen receptor modulators and methods of use thereof Inventor(s): Dalton, James T.; (Columbus, OH), He, Yali; (Florence, SC), Miller, Duane D.; (Germantown, TN), Yin, Donghua; (St. Louis, MO) Correspondence: Eitan, Pearl, Latzer, & Cohen-zedek; One Crystal Park, Suite 210; 2011 Crystal Drive; Arlington; VA; 22202-3709; US Patent Application Number: 20020099096 Date filed: August 23, 2001 Abstract: This invention provides a novel class of androgen receptor targeting agents (ARTA). The agents define a new subclass of compounds which are tissue-selective androgen receptor modulators (SARM), which are useful for oral testosterone replacement therapy, male contraception, maintaining sexual desire in women, treating prostate cancer and imaging prostate cancer. These agents have an unexpected in-vivo activity for an androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. These agents may be active alone or in combination with progestins or estrogens. The invention further provides a novel class of non-steroidal agonist compounds. The invention further provides compositions containing the selective androgen modulator compounds or the non-steroidal agonist compounds and methods of binding an androgen receptor, modulating spermatogenesis, treating and imaging prostate cancer, and providing hormonal therapy for androgen-dependent conditions. Excerpt(s): This Application claims the benefit of U.S. Ser. No. 09/644,970, filed Aug. 24, 2000 and claims priority of U.S. Ser. No. 60/300,083, filed Jun. 25, 2001, which are hereby incorporated by reference. The present invention relates to a novel class of tissueselective androgen receptor targeting agents (ARTA) which demonstrate androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. The agents define a new subclass of compounds which are tissue-selective androgen receptor modulators (SARM) which are useful for male hormone therapy such as oral testosterone replacement therapy, mate contraception, maintaining sexual desire in women, treating prostate cancer, and imaging prostate cancer. These agents are also administered to a subject for the treatment of sarcopenia, lack of sexual libido, osteoporosis, erythropoiesis, and fertility. The agents may be used alone or in combination with a progestin or estrogen. The androgen receptor ('AR'") is a ligandactivated transcriptional regulatory protein that mediates induction of male sexual development and function through its activity with endogenous androgens. Androgens are generally known as the male sex hormones. However, androgens also play a pivotal role in female physiology and reproduction. The androgenic hormones are steroids which are produced in the body by the testis and the cortex of the adrenal gland, or synthesized in the laboratory. Androgenic steroids play an important role in many physiologic processes, including the development and maintenance of male sexual characteristics such as muscle and bone mass, prostate growth, spermatogenesis, and the male hair pattern (Matsumoto, Endocrinol. Met. Clin. N. Am. 23:857-75 (1994). The endogenous steroidal androgens include testosterone and dihydrotestosterone ("DHT") Testosterone is the principal steroid secreted by the testes and is the primary circulatiag androgen found in the plasma of males. Testosterone is converted to DHT by the

Patents 191

enzyme 5 alpha-reductase in many peripheral tissues. DHT is thus thought to serve as the intracellular mediator for most androgen actions (Zhou, et al., Molec. Endocrinol. 9:208-18 (1995)). Other steroidal androgens include esters of testosterone, such as the cypionate, propionate, phenylpropionate, cyclopentylpropionate, isocarporate, enanthate, and decanoate esters, and other synthetic androgens such as 7-MethylNortestosterone ("MENT'") and its acetate ester (Sundaram et al., "7 Alpha-MethylNortestosterone(MENT): The Optimal Androgen For Male Contraception," Ann. Med., 25:199-205 (1993) ("Sundaram")). Because the AR is involved in male sexual development and function, the AR is a likely target for effecting male contraception or other forms of hormone replacement therapy. The AR also regulates female sexual function (i.e., libido), bone formation, and erythropoiesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Selective androgen receptor modulators and methods of use thereof Inventor(s): Dalton, James T.; (Columbus, OH), He, Yali; (Florence, SC), Miller, Duane D.; (Germantown, TN), Yin, Donghua; (St. Louis, MO) Correspondence: Eitan, Pearl, Latzer & Cohen-zedek; Suite 210; One Crystal Park; 2011 Crystal Drive; Arlington; VA; 22202-3709; US Patent Application Number: 20020173495 Date filed: February 28, 2002 Abstract: This invention provides a class of androgen receptor targeting agents (ARTA) The agents define a new subclass of compounds which are selective androgen receptor modulators (SARM) useful for oral testosterone replacement therapy. Several of the SARM compounds have been found to have an unexpected androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. Other SARM compounds have been found to have an unexpected antiandrogenic activity of a nonsteroidal ligand for the androgen receptor. In one embodiment, the SARM compounds bind irreversibly to an androgen receptor. In another embodiment, the SARM compounds bind reversibly to an androgen receptor. In another embodiment, the SARM compounds are alkylating agents. The novel selective androgen receptor modulator compounds of the present invention, either alone or as a composition, are useful for suppressing spermatogenesis, treating a subject having a hormone related condition, treating a subject suffering from prostate cancer, delaying the progression of prostate cancer, preventing the recurrence of prostate cancer, and treating the recurrence of prostate cancer. Excerpt(s): The present invention relates to a novel class of androgen receptor targeting agents (ARTA) which demonstrate androgenic or antiandrogenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. The agents define a new subclass of compounds which are selective androgen receptor modulators (SARMs) which are useful for male hormone therapy such as oral testosterone replacement therapy, treating prostate cancer, and imaging prostate cancer. The androgen receptor ("AR`) is a ligandactivated transcriptional regulatory protein that mediates induction of male sexual development and function through its activity with endogenous androgens. Androgens are generally known as the male sex hormones. The androgenic hormones are steroids which are produced in the body by the testes and the cortex of the adrenal gland, or synthesized in the laboratory. Androgenic steroids play an important role in many physiologic processes, including the development and maintenance of male sexual characteristics such as muscle and bone mass, prostate growth, spermatogenesis, and the male hair pattern (Matsumoto, Endocrinol. Met. Clin. N. Am. 23:857-75 (1994)). The

192 Testosterone

endogenous steroidal androgens include testosterone and dihydrotestosterone ("DHT"). Testosterone is the principal steroid secreted by the testes and is the primary circulating androgen found in the plasma of males. Testosterone is converted to DHT by the enzyme 5 alpha-reductase in many peripheral tissues. DHT is thus thought to serve as the intracellular mediator for most androgen actions (Zhou, et al., Molec. Endocrinol. 9:208-18 (1995)). Other steroidal androgens include esters of testosterone, such as the cypionate, propionate, phenylpropionate, cyclopentylpropionate, isocarporate, enanthate, and decanoate esters, and other synthetic androgens such as 7-MethylNortestosterone ("MENT`) and its acetate ester (Sundaram et al, "7 Alpha-MethylNortestosterone(MENT): The Optimal Androgen For Male Contraception," Ann. Med., 25:199-205 (1993) ("Sundaram")). Because the AR is involved in male sexual development and function, the AR is a likely target for effecting male contraception or other forms of hormone replacement therapy. Worldwide population growth and social awareness of family planning have stimulated a great deal of research in contraception. Contraception is a difficult subject under any circumstance. It is fraught with cultural and social stigma, religious implications, and, most certainly, significant health concerns. This situation is only exacerbated when the subject focuses on male contraception. Despite the availability of suitable contraceptive devices, historically, society has looked to women to be responsible for contraceptive decisions and their consequences. Although concern over sexually transmitted diseases has made men more aware of the need to develop safe and responsible sexual habits, women still often bear the brunt of contraceptive choice. Women have a number of choices from temporary mechanical devices such as sponges and diaphragms to temporary chemical devices such as spermicides. Women also have at their disposal more permanent options such as physical devices including IUDs and cervical caps as well as more permanent chemical treatments such as birth control pills and subcutaneous implants. However, to date, the only options available for men include the use of condoms and vasectomy. Condom use, however is not favored by many men because of the reduced sexual sensitivity, the interruption in sexual spontaneity, and the significant possibility of pregnancy caused by breakage or misuse. Vasectomies are also not favored. If more convenient methods of birth control were available to men, particularly long term methods which required no preparative activity mediately prior to a sexual act, such methods could significantly increase the likelihood that men would take more responsibility for contraception. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Semisolid topical hormonal compositions and methods for treatment Inventor(s): Azarnoff, Daniel L.; (Hillsborough, CA), Mak, Vivien H.W.; (Palo Alto, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030175329 Date filed: October 4, 2002 Abstract: Semisolid topical pharmaceutical compositions comprising a therapeutically effective amount of a mammalian hormone and an effective amount of a penetration enhancer and methods for their use are provided. The pharmaceutical compositions and methods for their use can provide blood or plasma levels of the administered hormone within a predetermined or normal range of hormone values. In particular embodiments, the hormone is testosterone or estrogen and the amount to be applied to the skin of the subject is determined according to the weight or body mass index of the subject. The topical composition can be formulated in solutions, creams, lotions, ointments, and gels.

Patents 193

Excerpt(s): This application claims priority from U.S. Patent Application No.60/327,423 filed Oct. 4, 2001 which is incorporated by reference in its entirety. This invention lies in the technology of the transdermal or topical treatment of human subjects with semisolid topical pharmaceutical compositions comprising therapeutically effective amounts of a mammalian hormone and an effective amount of a skin penetration enhancer. In particular, the present invention provides such pharmaceutical compositions and methods for their administration so as to provide blood or plasma levels of the administered hormone within a predetermined or normal range of hormone values. In particular embodiments, the hormone is testosterone or estrogen and the amount to be applied to the skin of the subject is according to the body weight or body mass index of the subject. During the past decade, the feasibility of the dermal route for systemic drug delivery has been established for a variety of therapeutic agents. Such transdermal therapeutic systems include those containing scopolamine, glyceryl trinitrate, clonidine, fentanyl, nicotine, testosterone and estradiol. Ultimately, the success of transdermal systems depends both on the ability of the drug to permeate the skin in sufficient quantities and at a sufficient rate to achieve the desired therapeutic effect and on the ability to adjust the dosage so as to increase or decrease the amount absorbed so as to assure an efficacious level is achieved without exceeding the threshold for adverse effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapy for andropause using estrogen agonists / antagonists and testosterone Inventor(s): MacLean, David B.; (Providence, RI) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159, Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020115676 Date filed: November 27, 2001 Abstract: The present invention concerns the treatment of andropause and related conditions using a combination of an estrogen agonist/antagonist and testosterone. Excerpt(s): This application claims priority of U.S. provisional application No. 60/250,071, filed Nov. 30, 2000. The present invention relates to methods and kits for the treatment of andropause and the conditions related to or resulting from andropause. More particularly, the present invention concerns the treatment of andropause and related conditions using a combination of an estrogen agonist antagonist and testosterone. Andropause (also called male menopause or viropause) is a natural occurrence in men that typically happens between the age of forty and fifty-five. Andropause is a decline in the level of the hormone testosterone. As testosterone levels decline, and men enter andropause, various changes or conditions may be observed including decreased energy and strength, increased body fat, osteoporosis, depression, decreased mental acuity, inability to maintain muscle, cardiovascular disease, atherosclerosis, decreased libido, decreased strength of orgasms, erectile dysfunction, increased irritability, and aching and stiff joints, particularly in the hands and feet. In addition, males undergoing or having undergone andropause can have gynecomastia, serum lipid disorders, including hypercholesterolemia, reduced vascular reactivity, hypogonadism, and benign prostatic hyperplasia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

194 Testosterone

•

Tissue engineered testicular prosthesis and use thereof Inventor(s): Atala, Anthony; (Weston, MA) Correspondence: David S. Resnick; Nixon Peabody Llp; 101 Fedral Street; Boston; MA; 02110; US Patent Application Number: 20020091448 Date filed: December 13, 2001 Abstract: The present invention provides a tissue engineered testicular prosthesis for implanting within a patient comprises a scaffold comprising a biodegradable polymer scaffold having a substantially elliptical body in longitudinal cross-section replicating the shape of a testicle and a substantially circular cross-section in transverse crosssection the biodegradable scaffold defining an interior and an exterior of the prosthesis and the scaffold being seeded with disassociated chondrocytes or Leydig cells, or both chondrocytes and Leydig cells. The interior of the prosthesis can be at least partially filled with testosterone. Excerpt(s): The present invention is generally directed to a tissue engineered (TE) testicular prosthesis having both cosmetic and therapeutic uses. Testicular dysfunction, characterized by either an absence of androgenic production, an absence of the testes. or both, has great medical and psychological consequences on the afflicted male population ranging from infertility and cancer to psychiatric disturbances. Causes of testicular dysfunction include chromosomal abnormalities, testicular torsion (which may be a result of inadequate connective tissue within the scrotum or trauma to the scrotum, after strenuous exercise or without an obvious cause; the incidence is higher during infancy and with the onset of adolescence) direct trauma to the testicles, diseases that affect the testicle (such as mumps orchitis and testicular cancer), and a variety of drugs. Increased risk is associated with activities that may cause constant, low level trauma to the scrotum (such as riding a motorcycle) or frequent administration of a drug known to affect testicular function (such as heavy marijuana use or taking some prescription medications). Thus, testicular dysfunction can result at the time of fetal development, adolescence and during the adult years. During fetal development, the fetal testes are formed within the abdominal cavity in the region where the kidneys are normally located in adults. They descend into their normal scrotal position shortly before birth. The prevalence of undescended testes (cryptorchidism) is 3.4% in full-term infants and as high as 30% in premature infants. The testes often descend after birth, and the prevalence of cryptorchidism by one year of age is down to 1%. Current practice is to surgically correct undescended testes at around age one year. The main reason for bringing the testes down early is to preserve future fertility. Testicular atrophy may be present due to a primary abnormality of the testis or due to damage incurred during surgery. A testicular prosthesis could be inserted for cosmetic reasons, but the undescended testicle may have to be removed to achieve the desired "normal" result. This undescended testes may be producing hormones and be worth sparing. However, the risks of inserting a testicular prosthesis are minimal and consist of infection (around 2%) and bruising. Physicians frequently recommend that a testicular prosthesis be placed early in life to prevent shrinkage of the scrotum which can occur when the sac is empty, and allow for normal psychological development through the patient's early years. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 195

•

Topical testosterone formulations and associated methods Inventor(s): Kryger, Abraham H.; (Monterey, CA) Correspondence: Thorpe North Western; 8180 South 700 East, Suite 200; P.O. Box 1219; Sandy; UT; 84070; US Patent Application Number: 20020150625 Date filed: December 11, 2001 Abstract: A topical testosterone formulation is disclosed. In one aspect, the formulation may include a therapeutically effective amount of micronized testosterone, an arginine ingredient, and a tocopherol ingredient admixed with a poloxamer lecithin organogel. Additional ingredients may be included, such as melatonin, oxytocin, DHEA, and progesterone. Excerpt(s): This application claims priority to United States Provisional Patent Application Serial No. 60/254,713, filed on Dec. 11, 2000, which is hereby incorporated by reference. The present invention relates to topical testosterone formulations, including methods for making and using such formulations. Accordingly, this invention covers the fields of pharmaceutical sciences and medicine. Hormone replacement therapy has been used in the past to treat patients who have lost the ability to make the hormones or who have reduced hormone levels. Further, testosterone replacement therapy has been used to treat patients with abnormally low testosterone levels. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Use of 4-androstenediol and 4-androstenediol in a transdermal formulation to increase testosterone levels in humans Inventor(s): Kucharchuk, Andrew; (Baton Rouge, LA), Patin, Merrill A.; (Baton Rouge, LA) Correspondence: Thomas S. Keaty; Keaty Professional Law CORP.; 2140 World Trade Center; NO. 2 Canal Street; New Orleans; LA; 70130; US Patent Application Number: 20030109512 Date filed: October 29, 2002 Abstract: A method of increasing testosterone level in humans by topical application of a cream or gel involves the use of an androgenic testosterone precursor and a protein precursor for elevating the symptoms of depression and lethargy associated with low level testosterone. The androgenic precursor is 4-androstenediol, the protein precursor is 5-hydroxytryptophan. The two active ingredients are mixed in therapeutically effective amounts with a penetrating cream or gel containing a formulation of lecithin, isopropyl palmitate, and pluronic.The resultant composition of matter is applied as a transdermal formulation. The testosterone level is increased, while the toxicity problems associated with conventional administration of testosterone are avoided. Excerpt(s): The present invention relates to a method of administering the testosterone precursor 4-androstenediol for increasing testosterone level in humans. Human males naturally produce the hormone testosterone substantially during the lifetime of the person. As the body ages, the level of testosterone slowly declines, causing bone mass loss, sexual dysfunction, lethargy, loss of muscle mass, and strength. To slow down the undesirable effects of aging, various techniques have been developed. Some of the techniques involve the process of introducing prohormones that are designed to

196 Testosterone

increase the testosterone level. This process includes the use of oral preparations, wherein a therapeutic agent is administered in the form of a pill. The major drawback of oral preparations of testosterone is the fact that they must be in a form that will allow their absorption from the gastrointestinal tract. The prohormones administered by the oral method are taken in an inactive form, absorbed and then activated in the liver in a process known as methylation. As can be expected, these preparations are fraught with liver dysfunction. The testosterone elevating drugs can be also introduced by injections. This is by far the most popular method of testosterone supplementation. The testosterone injections had been used since World War II. These provide nonphysiological blood levels; either supra physiological or infra-plhysiological, depending on the temporal proximity to the injection. Most often used compounds are testosterone cypionate and testosterone enanthate. These compounds are administered as a 200-mg injection every two to three weeks. The drawback of the injection method is that an initial super-physiologic testosterone level the first few days after the injection is followed by a decrease. The resultant peak-and-valley effect may have more long-term consequences than a steady level that may be produced by transdermal preparations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with testosterone, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “testosterone” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on testosterone. You can also use this procedure to view pending patent applications concerning testosterone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

197

CHAPTER 7. BOOKS ON TESTOSTERONE Overview This chapter provides bibliographic book references relating to testosterone. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on testosterone include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “testosterone” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on testosterone: •

Getting Help: A Patient's Guide for Men With Impotence Source: Lenexa, KS: Integrated Medical Resources, Inc. 1995. 48 p. Contact: Available from Integrated Medical Resources, Inc. 8326 Melrose Drive, Lenexa, KS 66214. (913) 894-0591. PRICE: $6.95. Summary: This handbook provides basic information about the diagnosis and treatment of male erectile dysfunction, or impotence. After introductory chapters defining impotence and discussing its causes, the author considers diagnostic issues, including the patient history and physical, specialized blood tests, erection monitoring during sleep, in-office impotence testing, and other specialized tests. The next chapter outlines treatment options, including sexual counseling, oral medications, testosterone hormone replacement, penile injections, vacuum constriction devices, penile implant surgery, and corrective surgeries. Also included is a chapter on penile curvature and Peyronie's disease. The handbook concludes with two brief sections to help readers determine if

198 Testosterone

they really have a problem and to encourage them to consult a health care provider. A brief index concludes the book. Simple line drawings illustrate many of the concepts.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “testosterone” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “testosterone” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “testosterone” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Andro Effect: Using Androstenedione to Enhance Testosterone Production by C. M. Hawken (1998); ISBN: 1580540422; http://www.amazon.com/exec/obidos/ASIN/1580540422/icongroupinterna

•

Cholesterol: Interactions With Testosterone and Cortisol in Cardiovascular Disease by Jens Miller; ISBN: 0387170979; http://www.amazon.com/exec/obidos/ASIN/0387170979/icongroupinterna

•

Effect of Testosterone on Craniofacial Growth in the Human & the Rat by An Verdonck (1997); ISBN: 9061868432; http://www.amazon.com/exec/obidos/ASIN/9061868432/icongroupinterna

•

Heroes, Rogues, & Lovers: Testosterone and Behavior by James McBride Dabbs, Mary Godwin Dabbs (Contributor); ISBN: 0071376283; http://www.amazon.com/exec/obidos/ASIN/0071376283/icongroupinterna

•

How to Naturally Increase Growth Hormone and Testosterone by Abazar Habibinia (2003); ISBN: 1410741338; http://www.amazon.com/exec/obidos/ASIN/1410741338/icongroupinterna

•

Social Structure and Testosterone: Explorations of the Socio-Bio-Social Chain by Theodore D. Kemper (1990); ISBN: 0813515505; http://www.amazon.com/exec/obidos/ASIN/0813515505/icongroupinterna

•

Super "T": The Complete Guide to Creating an Effective, Safe, and Natural Testosterone Supplement Program for Men and Women by Joshua Shackman, et al (1999); ISBN: 0684863359; http://www.amazon.com/exec/obidos/ASIN/0684863359/icongroupinterna

•

T.C. (Testosterone Curse: The Journal of E.Z. Gottcha by Mary Wells Noyes (1996); ISBN: 1887361030; http://www.amazon.com/exec/obidos/ASIN/1887361030/icongroupinterna

•

Testosterone by James Robert Baker (2001); ISBN: 155583714X; http://www.amazon.com/exec/obidos/ASIN/155583714X/icongroupinterna

•

Testosterone : a User's Manual by Christopher P. Steidle; ISBN: 0970811209; http://www.amazon.com/exec/obidos/ASIN/0970811209/icongroupinterna

•

Testosterone and The Art of Nesting by Carolyn Gabriel; ISBN: 1888368012; http://www.amazon.com/exec/obidos/ASIN/1888368012/icongroupinterna

Books

199

•

Testosterone Deficiency by A. Vermeulen; ISBN: 1842140434; http://www.amazon.com/exec/obidos/ASIN/1842140434/icongroupinterna

•

Testosterone Deficiency in Women by Gelfand (2004); ISBN: 1842141732; http://www.amazon.com/exec/obidos/ASIN/1842141732/icongroupinterna

•

Testosterone Dreams 69-00 by Scevans55 (2001); ISBN: 0759639760; http://www.amazon.com/exec/obidos/ASIN/0759639760/icongroupinterna

•

Testosterone Dreams: Rejuvenation, Aphrodisia, Doping by John M. Hoberman (2005); ISBN: 0520221516; http://www.amazon.com/exec/obidos/ASIN/0520221516/icongroupinterna

•

Testosterone Inc : Tales of CEOs Gone Wild by Christopher M. Byron (Author) (2004); ISBN: 0471420050; http://www.amazon.com/exec/obidos/ASIN/0471420050/icongroupinterna

•

Testosterone Planet: True Stories from a Man's World by Sean O'Reilly (Editor), et al (1999); ISBN: 1885211430; http://www.amazon.com/exec/obidos/ASIN/1885211430/icongroupinterna

•

Testosterone Replacement Therapy by Fred C. W. Wu; ISBN: 189809912X; http://www.amazon.com/exec/obidos/ASIN/189809912X/icongroupinterna

•

Testosterone Treatment of Cardiovascular Diseases: Principles and Clinical Experience by Jens Moller; ISBN: 0387130454; http://www.amazon.com/exec/obidos/ASIN/0387130454/icongroupinterna

•

Testosterone: Action, Deficiency, Substitution by E. Nieschlag, H.M. Behre (Editor); ISBN: 038752763X; http://www.amazon.com/exec/obidos/ASIN/038752763X/icongroupinterna

•

Testosterone: Sports Studies by Richard P. Braden (2002); ISBN: 0595218474; http://www.amazon.com/exec/obidos/ASIN/0595218474/icongroupinterna

•

The Hormone of Desire : The Truth About Testosterone, Sexuality, and Menopause by Susan Rako (1999); ISBN: 0609803867; http://www.amazon.com/exec/obidos/ASIN/0609803867/icongroupinterna

•

The Smart Guide to Andro: The Safe and Natural Testosterone Precursor for Sex and Athletic Enhancement by Lane Lenard; ISBN: 096274185X; http://www.amazon.com/exec/obidos/ASIN/096274185X/icongroupinterna

•

The Testosterone Advantage Plan : Lose Weight, Gain Muscle, Boost Energy by Lou Schuler (Author), et al; ISBN: 0743237919; http://www.amazon.com/exec/obidos/ASIN/0743237919/icongroupinterna

•

The Testosterone Revolution: Rediscover Your Energy and Overcome the Symptoms of Male Menopause by Malcolm Carruthers; ISBN: 0007122756; http://www.amazon.com/exec/obidos/ASIN/0007122756/icongroupinterna

•

The Testosterone Solution : Increase Your Energy and Vigor with Male Hormone Therapy by Aubrey Hill (Author); ISBN: 0761510222; http://www.amazon.com/exec/obidos/ASIN/0761510222/icongroupinterna

•

The Testosterone Syndrome by Eugene Shippen, William Fryer; ISBN: 087131858X; http://www.amazon.com/exec/obidos/ASIN/087131858X/icongroupinterna

•

The Trouble With Testosterone: And Other Essays On The Biology Of The Human Predicament by Robert M. Sapolsky (Author) (1998); ISBN: 0684838915; http://www.amazon.com/exec/obidos/ASIN/0684838915/icongroupinterna

200 Testosterone

•

The Virility Factor: Masculinity Through Testosterone, the Male Sex Hormone by Robert Bahr; ISBN: 096265311X; http://www.amazon.com/exec/obidos/ASIN/096265311X/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “testosterone” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Errors of phenylalanine, thyroxine, and testosterone metabolism; proceedings of the seventh annual symposium. held at the University of Glasgow, 10th and 11th July, 1969. Edited by William Hamilton and Frederick P. Hudson. Author: Society for the Study of Inborn Errors of Metabolism.; Year: 1958; Edinburgh, Livingstone, 1970; ISBN: 0443007101

•

Evaluation of the Biodata Testosterone MAIA kit from Serono Diagnostics Author: Abbey, T. Department of Chemical Pathology, St. Thomas' Hospital, London.; Year: 1986; London: Department of Health, 1991; ISBN: 1851976868

•

Evaluation of the CIS Testosterone-CT radioimmunoassay kit Author: Abbey, T. Department of Chemical Pathology, St. Thomas' Hospital, London.; Year: 1983; London: Department of Health, 1991

•

Evaluation of the Diria-Testok testosterone kit Author: Abbey, T. Department of Chemical Pathology, St. Thomas' Hospital, London.; Year: 1970; London: Department of Health, 1992; ISBN: 1851977007

•

Evaluation of the DPC Coat-a-Count Total testosterone kit Author: Kicman, A. DH Evaluation Unit, Department of Chemical Pathology, St Thomas' Hospital, London.; Year: 1985; London: Department of Health, 1990

•

Evaluation of the Medgenix Fertigenix radioimmunoassay kit for serum testosterone Author: Kicman, A. Department of Chemical Pathology, St. Thomas' Hospital, London.; Year: 1987; London: Department of Health, 1990

•

Monoaminergic influence on testosterone-activated copulatory behavior in the castrated male rat. Author: Malmnäs, Carl Olof.; Year: 1951; Uppsala, 1973

•

Progesterone and testosterone metabolism in gingival physiology and pathophysiology Author: Ojanotko-Harri, Anita.; Year: 1973; Turku: Institute of Dentistry, University of Turku, 1990; ISBN: 9518804567

•

Studies on selective uptake and metabolism of testosterone-3H in the prostate and the seminal vesicles of the rat Author: Tveter, Kjell J.; Year: 1968; Oslo: Universitetsforlaget, c1970

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

Books

201

•

Testosterone: action, deficiency, substitution Author: Nieschlag, E.; Year: 1979; Berlin; New York: Springer-Verlag, c1990; ISBN: 354052763X

•

Testosterone binding in human plasma. Author: Steeno, Omer.; Year: 1960; Leuven, Acco, 1970

•

The hormone of desire: the truth about sexuality, menopause, and testosterone Author: Rako, Susan.; Year: 1976; New York: Harmony Books, c1996; ISBN: 0517703424 http://www.amazon.com/exec/obidos/ASIN/0517703424/icongroupinterna

•

The virility factor: masculinity through testosterone, the male sex hormone Author: Bahr, Robert.; Year: 1976; New York: Putnam, c1976; ISBN: 039911808X http://www.amazon.com/exec/obidos/ASIN/039911808X/icongroupinterna

Chapters on Testosterone In order to find chapters that specifically relate to testosterone, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and testosterone using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “testosterone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on testosterone: •

Testosterone Effect: Hormone Replacement Therapy Source: in Newman, A.J. Beyond Viagra: Plain Talk About Treating Male and Female Sexual Dysfunction. Montgomery, AL: Starrhill Press. 1999. p. 64-66. Contact: Available from Black Belt Press. P.O. Box 551, Montgomery, AL 36101. (800) 959-3245 or (334) 265-6753. Fax (334) 265-8880. PRICE: $13.95 plus shipping and handling. ISBN: 1573590142. Summary: This chapter, from a book that discusses the drug sildenafil (Viagra) in the context of a larger discussion about sexuality and sexual dysfunction, discusses hormone replacement therapy (namely, testosterone). Testosterone replacement is currently used today in both primary and secondary hypogonadism (decreased testicular production of testosterone). The current methods of androgen replacement available for human use include oral preparations, the long acting esters of testosterone, and the transdermal preparations. The author describes how each of these preparations is used, and then discusses how low serum testosterone contributes to erectile dysfunction. Testosterone therapy is contraindicated in men with prostate cancer. It is relatively contraindicated in older men with bladder neck obstruction from prostate enlargement. The author recommends that all men over the age of 50 receiving testosterone first have a prostate specific antigen (PSA) level measurement and a digital rectal exam. In addition, because oral testosterone preparations definitely increase the risk of liver problems, requiring close monitoring of liver function. The chapter is written in nontechnical language but includes enough medical information to be of use to medical professionals wishing to learn more about sexuality and sexual dysfunction.

203

CHAPTER 8. MULTIMEDIA ON TESTOSTERONE Overview In this chapter, we show you how to keep current on multimedia sources of information on testosterone. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “testosterone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on testosterone: •

Testosterone Replacement Therapy for Sexual Dysfunction in HIV+ Men; the 16th National Lesbian & Gay Health Conference & 12th Annual AIDS/HIV Forum, New York, NY, June 21 - 26, 1994 Contact: Encore Cassettes, PO Box 231340, San Diego, CA, 92194, (619) 596-8402. Summary: This audio cassette recording describes testosterone replacement therapy for sexual dysfunction in HIV-positive men. The speaker details an 18-month study designed to research what effect testosterone replacement therapy has on sexual interest, erectile functioning, mood, energy, appetite, and weight. The demographics, psychological ratings, and medical characteristics necessary for inclusion in the study are outlined. The study procedure took place in two stages. Phase one results indicate significant improvement in sexual interest and functioning for those participants who completed the study. No ill side-effects were reported. The study conclusions of testosterone injection therapy imply a well tolerated treatment that provides good response to increased energy, mood, and appetite. Phase two consisted of a double blind placebo study. Results support phase one conclusions. In summation, the testosterone replacement therapy was pronounced an effective treatment because of its ability to make a difference in the perceived quality of life of the patients.

205

CHAPTER 9. PERIODICALS AND NEWS ON TESTOSTERONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover testosterone.

News Services and Press Releases One of the simplest ways of tracking press releases on testosterone is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “testosterone” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to testosterone. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “testosterone” (or synonyms). The following was recently listed in this archive for testosterone: •

Testosterone blockade may alter memory Source: Reuters Health eLine Date: December 12, 2003

•

Trials seen needed for anti-aging testosterone Source: Reuters Health eLine Date: November 12, 2003

206 Testosterone

•

Trials needed for use of testosterone as anti-aging drug Source: Reuters Industry Breifing Date: November 12, 2003

•

Testosterone helpful in postmenopausal women with decreased sexual desire Source: Reuters Industry Breifing Date: June 30, 2003

•

U.K. clears Auxilium testosterone gel Source: Reuters Industry Breifing Date: June 26, 2003

•

Testosterone taken with HRT may lower breast cancer risk Source: Reuters Industry Breifing Date: June 19, 2003

•

Schering launches topical testosterone gel in U.K. Source: Reuters Industry Breifing Date: June 13, 2003

•

Bright light may boost testosterone in me Source: Reuters Health eLine Date: April 30, 2003

•

Cellegy renames testosterone gel product at FDA's request Source: Reuters Industry Breifing Date: April 23, 2003

•

German launch of Schering testosterone gel planned for early May Source: Reuters Industry Breifing Date: April 16, 2003

•

Does testosterone boost an actor's Oscar odds? Source: Reuters Health eLine Date: March 21, 2003

•

Auxilium study shows Testim testosterone gel more effective than patch Source: Reuters Industry Breifing Date: March 14, 2003

•

Quintiles to promote Columbia's testosterone tablet in US Source: Reuters Industry Breifing Date: March 06, 2003

•

Estrogen and testosterone important for regulating bone growth in me Source: Reuters Industry Breifing Date: February 19, 2003

•

Estrogen, testosterone crucial in men's bone health Source: Reuters Health eLine Date: February 18, 2003

•

PDI says sued over testosterone gel promotion deal Source: Reuters Industry Breifing Date: February 13, 2003

•

Federal advisers mull testosterone for aging me Source: Reuters Health eLine Date: January 30, 2003

Periodicals and News

•

Alcohol may boost testosterone in brain and blood Source: Reuters Health eLine Date: January 15, 2003

•

Columbia Labs files in UK for testosterone replacement drug Source: Reuters Industry Breifing Date: December 03, 2002

•

Testosterone boost may help some with Parkinson's Source: Reuters Health eLine Date: November 26, 2002

•

Testosterone replacement therapy under scrutiny Source: Reuters Health eLine Date: November 06, 2002

•

Testosterone in blood linked to better memory Source: Reuters Health eLine Date: November 04, 2002

•

FDA clears new testosterone replacement gel Source: Reuters Industry Breifing Date: November 01, 2002

•

Columbia buccal testosterone tablet accepted for filing by FDA Source: Reuters Industry Breifing Date: October 21, 2002

•

Columbia Laboratories signs European marketing partner for buccal testosterone tablet Source: Reuters Industry Breifing Date: October 17, 2002

•

Testosterone fluctuation tied to women's sex drive Source: Reuters Health eLine Date: October 16, 2002

•

Columbia Labs files buccal testosterone product in US Source: Reuters Industry Breifing Date: August 09, 2002

•

Schering buys European rights to testosterone drug Source: Reuters Industry Breifing Date: July 02, 2002

•

Premenopausal women with low libido can benefit from transdermal testosterone Source: Reuters Industry Breifing Date: June 17, 2002

•

Testosterone linked to mental ability in older me Source: Reuters Health eLine Date: April 29, 2002

•

Testosterone but not estradiol linked to cognitive function in older me Source: Reuters Industry Breifing Date: April 22, 2002

•

Testosterone boosts mood in men with heart disease Source: Reuters Health eLine Date: April 10, 2002

207

208 Testosterone

•

Testosterone supplementation may reduce depression in men with CHF Source: Reuters Industry Breifing Date: April 09, 2002

•

Cellegy testosterone gel enters phase II/III female sexual dysfunction trial Source: Reuters Industry Breifing Date: March 26, 2002

•

Testosterone may be secret to home team advantage Source: Reuters Health eLine Date: March 18, 2002

•

High blood pressure tied to low testosterone Source: Reuters Health eLine Date: March 18, 2002

•

FDA to review topical testosterone drug based on Bentley's delivery system Source: Reuters Industry Breifing Date: March 06, 2002

•

Testosterone injection after severe burns reduces muscle catabolism Source: Reuters Industry Breifing Date: November 12, 2001

•

Testosterone boosts mental function in older me Source: Reuters Health eLine Date: July 17, 2001

•

Testosterone supplementation improves cognitive function in healthy older me Source: Reuters Industry Breifing Date: July 16, 2001

•

Solvay and TAP to co-market AndroGel in the US Source: Reuters Industry Breifing Date: May 30, 2001

•

3M completes phase I trial of next generation testosterone patch Source: Reuters Industry Breifing Date: April 27, 2001

•

Columbia reports positive phase II data on testosterone replacement drug, launches phase III trials Source: Reuters Industry Breifing Date: January 29, 2001

•

Testosterone implants effective contraception for me Source: Reuters Health eLine Date: December 26, 2000 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.


209

Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “testosterone” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “testosterone” (or synonyms). If you know the name of a company that is relevant to testosterone, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “testosterone” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “testosterone” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on testosterone: •

Weight and Cancer: More Links Uncovered Source: Tufts University Health and Diet Letter. 20(7): 1,8. September 2002.

210 Testosterone

Contact: P.O. Box 420235, Palm Coast, FL 32142-0235. 800/274-7581. www.healthletter.tufts.edu. Summary: Excess body fat seems to produce changes in the body that may contribute to the development of certain cancers. Research indicates that fat cells secrete growthproducing substances, including hormones, into the bloodstream. These substances send signals that prompt cells elsewhere in the body to grow and divide faster than they would otherwise. This in turn increases the risk that a random mutation could lead to the runaway cell growth of cancer. The cancers most affected by excess weight seem to be those related to the sex hormones estrogen and testosterone. They include cancers of the breast, endometrium, and prostate. Excess body fat may also contribute to cancer through insulin. People who are overweight may produce extra insulin, which can increase cell division and therefore cancer risk. Risk increases as weight increases, but even a 5 percent reduction in body weight translates into a significant safeguard against future illness. •

Boning Up on Bone Health Source: University of California, Berkeley, Wellness Letter. 16(12):5. September 2000. Contact: Health Letter Associates. P.O. Box 412, Prince Street Station, New York, NY 10012-0007. Summary: Strong bones are dependent on more than just the mineral calcium. Depending on many factors, including testosterone in men and estrogen in women, calcium is laid down in bone and released from it. Weight-bearing exercise such as walking synergizes with nutrients and hormones to build up bone tissue. Lack of activity robs the body of bone mass. The article reviews the other nutrients besides calcium that are necessary for bone health: vitamin C, vitamin K, vitamin D, magnesium, potassium, zinc, copper, manganese, and boron. These nutrients can be found in diets rich in fruits, whole grains, vegetables, low-fat and non-fat dairy products, and fortified cereals. The author also recommends a daily multivitamin and mineral supplement for most people.

•

Glucocorticoid-Induced Osteoporosis: Prevention and Treatment Source: Bulletin on the Rheumatic Diseases. 49(4): 1-4. 2000. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on the pathogenesis and clinical course of glucocorticoid induced osteoporosis (GIOP) and the management options for both primary prevention and treatment. Bone loss from glucocorticoids is related to dose and duration of treatment, hormonal status, genetics, and baseline bone mineral density (BMD). Glucocorticoids are associated with a decrease in gonadal hormones that can accelerate bone resorption and decrease bone formation, and they interfere with osteoblast maturation and accelerate apoptosis. In addition, they decrease calcium absorption from the gastrointestinal tract and increase renal excretion of calcium. Baseline BMD should be determined, and bone preserving therapy should begin at the initiation of glucocorticoid treatment. Patients receiving glucocorticoids should take calcium and vitamin D supplements. Other preventive measures that should be considered include treatment with bisphosphonates, calcitonin, and estrogen and testosterone replacements. The article also presents an approach to


211

management of GIOP in patients who have normal BMD, patients who have osteopenia, and patients who have osteoporosis. 33 references. •

Lupus in Men Source: Lupus News. 18(3): 8-9. Summer 1998. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article provides men who have systemic lupus erythematous (SLE) with information on this chronic disease. Although SLE is usually thought of as a disease of women of childbearing age, after the age of 50, the percentage of women with the disease falls and the percentage of men with the disease rises. The role of sex hormones in the development and clinical expression of SLE is complex. Some studies have noted lower levels of testosterone in some men who have SLE. Several studies have attempted to determine clinical differences between men and women who have SLE. Although the percentages of certain symptoms may be different in men and women, the manifestations are similar, including SLE associated arthritis and some skin lesions. Drug induced lupus is more common in men because the disorders for which some medications are used are diagnosed more often in men. Although both men and women diagnosed with SLE face many similar challenges, men must cope with the difficulty of discussing a disease that so many people believe occurs only in women and meeting other men who have it. The article includes a report on a trial of the weak androgen, dehydroepiandrosterone, in men with lupus. 1 table and 5 references.

•

Anatomy of an Itch Source: Quarterly: The Journal of the National Pemphigus Foundation. 27: 10. Winter 2001. Contact: Available from National Pemphigus Foundation. P.O. Box 9606, Berkeley, CA 94709-0606. (510) 527-4970. Fax: (510) 527-8497. Email: [email protected]. Website: www.pemphigus.org. Summary: This newsletter article provides tips for alleviating itching for patients with pemphigus. Antihistamines may help control itching, as well as wearing cotton clothing, staying indoors when it is hot outside, reducing stress, and using moisturizers and soap substitutes. A number of drugs such as anabolic steroids, B complex vitamins, estrogen, and testosterone should be avoided. Alcohol can also cause itching by changing the amount of blood flowing to the skin. For many people itching precedes the appearance of skin lesions.

Academic Periodicals covering Testosterone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to testosterone. In addition to these sources, you can search for articles covering testosterone that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.”

212 Testosterone

If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

213

CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for testosterone. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with testosterone. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

214 Testosterone

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to testosterone: Anabolic Steroids •

Systemic - U.S. Brands: Anadrol-50; Deca-Durabolin; Durabolin; Durabolin-50; Hybolin Decanoate; Hybolin-Improved; Kabolin; Oxandrin; Winstrol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202035.html

Androgens •

Systemic - U.S. Brands: Andro L.A. 200; Androderm; AndroGel 1%; Android; Android-F; Andronate 100; Andronate 200; Andropository 200; Andryl 200; Delatest; Delatestryl; Depotest; Depo-Testosterone; Everone 200; Halotestin; ORETON Methyl; T-Cypionate; Testamone 100; Testaqua; Te http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202036.html

Androgens and Estrogens •

Systemic - U.S. Brands: Andrest 90-4; Andro-Estro 90-4; Androgyn L.A.; DeComberol; Deladumone; Delatestadiol; depAndrogyn; Depo-Testadiol; Depotestogen; Duo-Cyp; Duo-Gen L.A.; Dura-Dumone 90/4; Duratestin; Estratest; Estratest H.S.; Halodrin; Menoject-L.A.; OB; Premarin with http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202037.html

Chorionic Gonadotropin •

Systemic - U.S. Brands: A.P.L.; Pregnyl; Profasi http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202266.html

Follitropin Alfa •

Systemic - U.S. Brands: Gonal-F http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203454.html

Goserelin •

Systemic - U.S. Brands: Zoladex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202267.html

Histrelin •

Systemic - U.S. Brands: Supprelin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203510.html

Leuprolide •

Systemic - U.S. Brands: Lupron; Viadur http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202322.html

Nafarelin •

Systemic - U.S. Brands: Synarel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202646.html

Researching Medications

215

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to testosterone by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “testosterone” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

216 Testosterone

marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for testosterone: •

Testosterone (trade name: TheraDerm Testosterone Transdermal System) http://www.rarediseases.org/nord/search/nodd_full?code=850

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

217

APPENDICES

219

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

220 Testosterone

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

221

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

222 Testosterone

•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “testosterone” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “testosterone” (or synonyms) into the “For these words:” box. The following is a sample result: •

D.H.E.A. (Dehydroepiandrosterone) Contact: AIDS Project Los Angeles, 3550 Wilshire Blvd Ste 300, Los Angeles, CA, 900102404, (213) 201-1600, http://www.apla.org. Summary: This report provides information on DHEA (EL-10, Dehydroepiandrosterone), a major adrenal secretory product in men and women which is though to be an intermediate in the biosynthesis of testosterone, by compound name, description, its clinical trials and studies status, and availability. While very little in the way of clinical studies has been done, limited information can be obtained from a study done in Paris. It contains several articles on the advantages and disadvantages of DHEA, the results of clinical studies, and information on dosages, availability, and side effects. It indicates that DHEA has shown moderate selective inhibitory effects on HIV replication in vitro in HIV-infected lymphocytes and macrophages.

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “testosterone” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category.

15 16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

Physician Resources

223

Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 58946 912 811 94 4 60767

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “testosterone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

The HSTAT URL is http://hstat.nlm.nih.gov/.

19

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

224 Testosterone

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Testosterone In the following section, we will discuss databases and references which relate to the Genome Project and testosterone. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “testosterone” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for testosterone: •

Testosterone-binding Beta-globulin Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?187450 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: 23

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

Physician Resources

225

•

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

226 Testosterone

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “testosterone” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.

24

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

Physician Resources

227

The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “testosterone” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

25

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

229

APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on testosterone can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to testosterone. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to testosterone. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “testosterone”:

230 Testosterone

•

Other guides Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Male Genital Disorders http://www.nlm.nih.gov/medlineplus/malegenitaldisorders.html Men's Health Issues http://www.nlm.nih.gov/medlineplus/menshealthissues.html Sexual Health Issues http://www.nlm.nih.gov/medlineplus/sexualhealthissues.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on testosterone. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Testosterone and Impotence Source: Washington, DC: Impotence Institute of America, Inc. 199x. 2 p. Contact: Available from Impotence Institute of America. 10400 Little Pawtuxent Parkway, Suite 485, Columbia, MD 21044. (410) 715-9605. PRICE: Contact organization directly. Summary: This fact sheet discusses the role of testosterone in male impotence. Topics include daily changes in serum testosterone levels; decreases in serum testosterone that occur with aging; how testosterone levels affect sexual function; sexual response after testosterone injections; diagnostic and patient selection issues; and present research into the mechanism of normal erectile function. The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to testosterone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals

Patient Resources

231

and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to testosterone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with testosterone. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about testosterone. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/.

232 Testosterone

Simply type in “testosterone” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “testosterone”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “testosterone” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “testosterone” (or a synonym) into the search box, and click “Submit Query.”

233

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

234 Testosterone

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

235

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

236 Testosterone

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

237

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

238 Testosterone

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

239

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on testosterone: •

Basic Guidelines for Testosterone Testosterone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003707.htm

•

Signs & Symptoms for Testosterone Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm

•

Diagnostics and Tests for Testosterone 17-ketosteroids Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003460.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm LH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003708.htm

240 Testosterone

Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm •

Background Topics for Testosterone Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Testes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002334.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

241

TESTOSTERONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 17-Ketosteroids: Steroids that contain a ketone group at position 17. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acrosome: Cap-like structure covering the nucleus and anterior part of the sperm head. [NIH]

Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH]

242 Testosterone

Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adnexa: The appendages of the eye, as the lacrimal apparatus, the eyelids, and the extraocular muscles. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affective Symptoms: Mood or emotional responses dissonant with or inappropriate to the behavior and/or stimulus. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH]

Dictionary 243

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on

244 Testosterone

homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allium: A genus of liliaceous herbs containing onions (Allium cepa), garlic (Allium sativum), and others; many produce pungent, often bacteriostatic and physiologically active compounds and are used as food, condiment, and medicament, the latter in traditional medicine. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-Globulins: Serum proteins that have the most rapid migration during electrophoresis. This subgroup of globulins is divided into faster and slower alpha(1)- and alpha(2)-globulins. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form

Dictionary 245

proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen suppression: Treatment to suppress or block the production of male hormones. Androgen suppression is achieved by surgical removal of the testicles, by taking female sex hormones, or by taking other drugs. Also called androgen ablation. [NIH] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH]

246 Testosterone

Androstenediols: Unsaturated androstane derivatives which are substituted with two hydroxy groups in any position in the ring system. [NIH] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]

Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this

Dictionary 247

binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apnea: A transient absence of spontaneous respiration. [NIH]

248 Testosterone

Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU]

Dictionary 249

Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH]

250 Testosterone

Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azoospermia: Absence of spermatozoa in the semen, or failure of formation of spermatozoa. [EU]

Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Balloon Dilatation: Nonoperative repair of occluded vessels, ducts, or valves by insertion of a balloon catheter. It is used, amoung other things, to treat varices, torn retinas, renal and biliary calculi, gastric, bronchial and rectal stenoses, and heart valves, and includes catheterization with Fogarty and Foley catheters. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Dictionary 251

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Betahistine: N-Methyl-2-pyridineethanamine. A physiological histamine analog vasodilator agent that also acts as a histamine H1 receptor agonist. It is used in Meniere's disease and in vascular headaches but may exacerbate bronchial asthma and peptic ulcers. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bicalutamide: An anticancer drug that belongs to the family of drugs called antiandrogens. [NIH]

Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biodegradation: The series of processes by which living organisms degrade pollutant chemicals, organic wastes, pesticides, and implantable materials. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a

252 Testosterone

living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is

Dictionary 253

most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Neoplasms: Tumors or cancer of the breast. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH]

254 Testosterone

Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbidopa: A peripheral inhibitor of dopa decarboxylase. It is given in parkinsonism along with levodopa to inhibit the conversion of levodopa to dopamine in the periphery, thereby reducing the peripheral adverse effects, increasing the amount of levodopa that reaches the

Dictionary 255

central nervous system, and reducing the dose needed. It has no antiparkinson actions when given alone. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH]

256 Testosterone

Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudalis: Brain region that controls singing processes. [NIH] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon

Dictionary 257

differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chlordiazepoxide: An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawl. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or

258 Testosterone

transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clitoral: Pertaining to the clitoris. [EU] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH]

Dictionary 259

Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names.

260 Testosterone

Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU]

Dictionary 261

Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraceptive Agents: Chemical substances that prevent or reduce the probability of conception. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convalescence: The period of recovery following an illness. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a

262 Testosterone

single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cotinine: 1-Methyl-5-(3-pyridyl)-2-pyrrolidinone antidepressant. Synonym: Scotine. [NIH]

fumarate.

Stimulant

proposed

as

Dictionary 263

Coumarin: A fluorescent dye. [NIH] Coumestrol: A coumarin derivative occurring naturally in forage crops which has estrogenic activity. [NIH] Courtship: The mutual attraction between individuals of the opposite sex. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryptorchidism: A condition in which one or both testicles fail to move from the abdomen, where they develop before birth, into the scrotum. Cryptorchidism may increase the risk for development of testicular cancer. Also called undescended testicles. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types,

264 Testosterone

including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a

Dictionary 265

bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Desogestrel: A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] DHEA: Dehydroepiandrosterone. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH]

266 Testosterone

Dilator: A device used to stretch or enlarge an opening. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diurnal: Occurring during the day. [EU] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopa Decarboxylase: One of the aromatic-l-amino-acid decarboxylases, this enzyme is responsible for the conversion of dopa to dopamine. It is of clinical importance in the

Dictionary 267

treatment of Parkinson's disease. EC 4.1.1.28. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH]

268 Testosterone

Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emetic: An agent that causes vomiting. [EU] Emollient: Softening or soothing; called also malactic. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory

Dictionary 269

laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enanthate: An oily injectable contraceptive given every 8 weeks. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinologist: A doctor that specializes in diagnosing and treating hormone disorders. [NIH]

Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]

Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterovirus: A genus of the family Picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species

270 Testosterone

designated "human enterovirus". [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epitestosterone: 17 alpha-Hydroxy-androst-4-ene-3-one. A naturally occurring stereoisomer of testosterone with androgenic activity. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoiesis: The production of erythrocytes. [EU]

Dictionary 271

Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Ethisterone: 17 alpha-Hydroxypregn-4-en-20-yn-3-one. A synthetic steroid hormone with progestational effects. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by

272 Testosterone

determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH]

Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extraocular: External to or outside of the eye. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.

Dictionary 273

[NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can

274 Testosterone

be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoxymesterone: An anabolic steroid that has been used in the treatment of male hypogonadism, delayed puberty in males, and in the treatment of breast neoplasms in women. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frail Elderly: Older adults or aged individuals who are lacking in general strength and are unusually susceptible to disease or to other infirmity. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Frostbite: Damage to tissues as the result of low environmental temperatures. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Galanin: A neurotransmitter. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallic Acid: A colorless or slightly yellow crystalline compound obtained from nutgalls. It is used in photography, pharmaceuticals, and as an analytical reagent. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-Globulins: Serum globulins that migrate in the gamma region on electrophoresis. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangliosides: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of

Dictionary 275

proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Geriatric Assessment: Evaluation of the level of physical, physiological, or mental functioning in the older population group. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history,

276 Testosterone

physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid

Dictionary 277

(glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gonorrhoea: Infection due to Neisseria gonorrhoeae transmitted sexually in most cases, but also by contact with infected exudates in neonatal children at birth, or by infants in households with infected inhabitants. It is marked in males by urethritis with pain and purulent discharge, but is commonly asymptomatic in females, although it may extend to produce suppurative salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. Bacteraemia occurs in both sexes, resulting in cutaneous lesions, arthritis, and rarely meningitis or endocarditis. Formerly called blennorrhagia and blennorrhoea. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH]

278 Testosterone

Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Handedness: Preference for using right or left hand. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels

Dictionary 279

of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatocyte: A liver cell. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotropic: Of organisms that cannot live without an external source of organic food. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hidradenitis: The inflammation of a sweat gland (usually of the apocrine type). The condition can be idiopathic or occur as a result of or in association with another underlying condition. Neutrophilic eccrine hidradenitis is a relatively rare variant that has been reported in patients undergoing chemotherapy, usually for non-Hodgkin lymphomas or leukemic conditions. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU]

280 Testosterone

Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]

Dictionary 281

Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypospadias: A developmental anomaly in the male in which the urethra opens on the underside of the penis or on the perineum. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU]

282 Testosterone

Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysteroscopy: Endoscopic examination, therapy or surgery of the interior of the uterus. [NIH]

Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU]

Dictionary 283

Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH]

284 Testosterone

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are

Dictionary 285

distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation,

286 Testosterone

interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lacrimal: Pertaining to the tears. [EU] Lacrimal Apparatus: The tear-forming and tear-conducting system which includes the lacrimal glands, eyelid margins, conjunctival sac, and the tear drainage system. [NIH] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large

Dictionary 287

intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH]

288 Testosterone

Leydig Cells: Cells in the interstitial tissue of the testis that are believed to furnish the internal secretion of that gland. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to

Dictionary 289

cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Litter Size: The number of offspring produced at one birth by an animal. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH]

290 Testosterone

Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Luteinizing hormone-releasing hormone agonist: LH-RH agonist. A drug that inhibits the secretion of sex hormones. In men, LH-RH agonist causes testosterone levels to fall. In women, LH-RH agonist causes the levels of estrogen and other sex hormones to fall. [NIH] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e.,

Dictionary 291

extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megestrol: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [NIH] Megestrol Acetate: A drug that belongs to the group of hormones called progestins, used as hormone therapy to block estrogen and to suppress the effects of estrogen and androgens. [NIH]

Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH]

292 Testosterone

Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH] Mercuric Chloride: Mercury chloride (HgCl2). A highly toxic compound that volatizes slightly at ordinary temperature and appreciably at 100 degrees C. It is corrosive to mucous membranes and used as a topical antiseptic and disinfectant. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methyltestosterone: A synthetic hormone used for androgen replacement therapy and as an hormonal antineoplastic agent. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH]

Dictionary 293

Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Conformation: The characteristic three-dimensional shape of a molecule. [NIH] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration,

294 Testosterone

pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH]

Dictionary 295

Muscle Fatigue: A state arrived at through prolonged and strong contraction of a muscle. Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH]

296 Testosterone

Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with

Dictionary 297

atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

298 Testosterone

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue

Dictionary 299

spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oestradiol: Growth hormone. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oligoribonucleotides: A group of ribonucleotides (up to 12) in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver

300 Testosterone

somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orchiectomy: The surgical removal of one or both testicles. [NIH] Orchitis: Inflammation of a testis. The disease is marked by pain, swelling, and a feeling of weight. It may occur idiopathically, or it may be associated with conditions such as mumps, gonorrhoea, filarial disease, syphilis, or tuberculosis. [EU] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovarian Cysts: General term for cysts and cystic diseases of the ovary. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH]

Dictionary 301

Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxazepam: A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpitation: A subjective sensation of an unduly rapid or irregular heart beat. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasympathetic Nervous System: The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. [NIH]

302 Testosterone

Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parent-Child Relations: The interactions between parent and child. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penile Erection: The state of the penis when the erectile tissue becomes filled with blood and causes the penis to become rigid and elevated. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH]

Dictionary 303

Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH]

304 Testosterone

Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of Raynaud's disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Pheromone: A substance secreted externally by certain animal species, especially insects, to affect the behavior or development of other members of the species. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or

Dictionary 305

glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photoperiod: The time period of daily exposure that an organism receives from daylight or artificial light. It is believed that photoperiodic responses may affect the control of energy balance and thermoregulation. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH]

306 Testosterone

Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plasticizers: Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polyglutamic Acid: A peptide that is a homopolymer of glutamic acid. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by

Dictionary 307

covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Population Growth: Increase, over a specific period of time, in the number of individuals living in a country or region. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain

308 Testosterone

conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Pregnenolone: Steroid hormone. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]

Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Priapism: Persistent abnormal erection of the penis, usually without sexual desire, and accompanied by pain and tenderness. It is seen in diseases and injuries of the spinal cord, and may be caused by vesical calculus and certain injuries to the penis. [EU] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH]

Dictionary 309

Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prolactinoma: A pituitary adenoma which secretes prolactin, leading to hyperprolactinemia. Clinical manifestations include amenorrhea; galactorrhea; impotence; headache; visual disturbances; and cerebrospinal fluid rhinorrhea. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond

310 Testosterone

(5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to

Dictionary 311

ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudorabies: A highly contagious herpesvirus infection affecting the central nervous system of swine, cattle, dogs, cats, rats, and other animals. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosexual: Pertaining to the mental aspects of sex. [NIH] Psychotomimetic: Psychosis miming. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH]

312 Testosterone

Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing

Dictionary 313

antibody formation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiosensitization: The use of a drug that makes tumor cells more sensitive to radiation therapy. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH]

314 Testosterone

Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal cell cancer: Cancer that develops in the lining of the renal tubules, which filter the blood and produce urine. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH]

Dictionary 315

Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Rhythmicity: Regular periodicity. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH]

316 Testosterone

Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sampling Studies: Studies in which a number of subjects are selected from all subjects in a defined population. Conclusions based on sample results may be attributed only to the population sampled. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Seborrhea: Hypersecretion of sebum with excessive oily secretion from the sweat glands. [NIH]

Seborrhoea: 1. Excessive secretion of sebum; called also hypersteatosis 2. Seborrhoeic dermatitis. [EU] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH]

Dictionary 317

Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous Epithelium: Specialized epithelium lining the seminiferous tubules containing developing and mature spermatozoa and Sertoli cells. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU]

318 Testosterone

Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the

Dictionary 319

GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other

320 Testosterone

diseases. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Songbirds: Passeriformes of the suborder, Oscines, in which the flexor tendons of the toes are separate, and the lower syrinx has 4 to 9 pairs of tensor muscles inserted at both ends of the tracheal half rings. They include many commonly recognized birds such as crows, finches, robins, sparrows, and swallows. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sperm Head: The anterior, usually ovoid, nucleus-containing part of spermatozoa. [NIH] Spermatic: A cord-like structure formed by the vas deferens and the blood vessels, nerves and lymphatics of the testis. [NIH] Spermatids: Male germ cells derived from spermatocytes and developing into spermatozoa. [NIH]

Spermatocytes: Male germ cells derived from spermatogonia and developing into spermatids. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatogonia: The spermatocytes. [NIH]

primitive

differentiated

male

gametes

which

give

rise

to

Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in

Dictionary 321

the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stanozolol: Anabolic agent. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [NIH] Streptozocin: An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]

322 Testosterone

Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Surgical castration: Surgical removal of the testicles (orchiectomy) or ovaries (oophorectomy) to stop the production of sex hormones. Decreasing the levels of hormones may stop the growth of certain cancers. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's

Dictionary 323

response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Syrinx: A fistula. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH]

324 Testosterone

Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terfenadine: A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug is used in the treatment of seasonal allergic rhinitis, asthma, allergic conjunctivitis, and chronic idiopathic urticaria. [NIH] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Territoriality: Behavior in defense of an area against another individual or individuals primarily of the same species. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahymena: A genus of ciliate protozoa commonly used in genetic, cytological, and other research. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH]

Dictionary 325

Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen

326 Testosterone

plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Toothache: Pain in the adjacent areas of the teeth. [NIH] Topical: On the surface of the body. [NIH] Torsades de Pointes: A ventricular tachycardia characterized by periodic twisting of the points of the QRS complexes and rates between 200 and 250 beats per minute. It may be selflimited or may progress to ventricular fibrillation. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH]

Dictionary 327

Transurethral: Performed through the urethra. [EU] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Truncal: The bilateral dissection of the abdominal branches of the vagus nerve. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other

328 Testosterone

mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urbanization: The process whereby a society changes from a rural to an urban way of life. It refers also to the gradual increase in the proportion of people living in urban areas. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Uridine Diphosphate Glucuronic Acid: A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. [NIH]

Dictionary 329

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Headaches: A group of disorders characterized by recurrent headaches associated with abnormal dilation and constriction of cerebral blood vessels. Representative disorders from this category include migraine, cluster headache, and paroxysmal hemicrania. [NIH] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]

Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH]

330 Testosterone

Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilism: Development of masculine traits in the female. [NIH] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the voice. Called also masculinization) [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH]

Dictionary 331

Vocal cord: The vocal folds of the larynx. [NIH] Void: To urinate, empty the bladder. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]

Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

333

INDEX 1 17-Ketosteroids, 239, 241 A Abdomen, 241, 253, 263, 285, 289, 301, 304, 315, 321, 325, 329, 330 Abdominal, 137, 160, 194, 241, 242, 285, 301, 304, 315, 327 Abdominal fat, 137, 160, 241 Ablation, 33, 35, 241, 245 Acantholysis, 241, 302 Acceptor, 241, 288, 301 Acetaminophen, 35, 241 Acetylcholine, 241, 257, 297 Acne, 55, 147, 159, 163, 241, 263, 330 Acrosome, 113, 124, 241 Actin, 29, 105, 241, 295, 327 Activities of Daily Living, 28, 63, 138, 241 Acuity, 193, 241 Adaptability, 241, 256 Adaptation, 241, 306 Adenine, 241, 242 Adenocarcinoma, 115, 137, 242, 310 Adenoma, 70, 242, 309 Adenosine, 173, 242, 249, 254, 305 Adenylate Cyclase, 53, 242 Adipocytes, 242, 261, 287 Adipose Tissue, 19, 241, 242 Adjustment, 49, 97, 241, 242 Adjuvant, 33, 117, 141, 155, 164, 242 Adnexa, 184, 242 Adolescence, 8, 18, 21, 46, 81, 166, 194, 242 Adrenal Cortex, 158, 171, 242, 246, 262, 271, 280, 281, 299, 309, 314 Adrenal Glands, 164, 175, 242 Adrenal Medulla, 242, 255, 270, 298 Adrenergic, 5, 173, 183, 242, 249, 267, 270, 304, 309, 323, 328, 331 Adverse Effect, 42, 45, 147, 158, 171, 193, 242, 248, 254, 318 Aerobic, 242, 271, 293, 301 Aerobic Metabolism, 242, 301 Aerobic Respiration, 242, 301 Aerosol, 173, 174, 242, 322 Affective Symptoms, 45, 242 Afferent, 242, 272, 285, 287, 308 Affinity, 10, 37, 55, 74, 243, 249, 288, 319 Agar, 243, 305 Age of Onset, 243, 328

Ageing, 85, 172, 243 Airway, 7, 243, 253, 319 Albumin, 105, 172, 243, 306 Alertness, 243, 254 Algorithms, 243, 252 Alimentary, 243, 286, 302, 303 Alkaline, 243, 245, 254, 304 Alkaloid, 243, 249, 259, 294, 297, 316, 331 Alkylating Agents, 191, 243 Alleles, 39, 243, 279 Allergen, 244, 317 Allergic Rhinitis, 244, 324 Allium, 7, 244 Allylamine, 244 Alopecia, 146, 178, 244 Alpha Particles, 244, 312 Alpha-Globulins, 105, 244 Alternative medicine, 209, 244 Alveolar Process, 244, 315 Ameliorated, 158, 171, 244 Ameliorating, 52, 151, 175, 183, 244 Amenorrhea, 125, 244, 246, 306, 309 Amine, 166, 244, 279 Amino Acid Sequence, 244, 245, 246, 318 Amino Acids, 145, 244, 246, 249, 297, 303, 307, 311, 328 Ammonia, 244, 245, 322, 328 Amnestic, 245, 293 Amniotic Fluid, 245, 276 Amphetamine, 40, 245, 265 Amyloid, 4, 66, 245 Anabolic Steroids, 211, 214, 245 Anaesthesia, 245, 283 Anal, 8, 26, 245, 270, 273, 289 Analgesic, 51, 241, 245, 269, 282, 287, 294, 300 Analog, 17, 25, 245, 251, 286, 287, 298 Analogous, 33, 169, 245, 326 Analysis of Variance, 25, 245 Anaplasia, 245, 310 Anatomical, 7, 169, 245, 249, 261, 283, 302, 316 Androgen suppression, 141, 245 Androgen-Binding Protein, 245, 318 Androstenediols, 147, 246 Androstenedione, 11, 12, 20, 22, 44, 76, 78, 79, 126, 131, 147, 153, 154, 198, 246 Anemia, 70, 225, 246

334 Testosterone

Anesthesia, 243, 246, 293, 308 Angiogenesis, 10, 72, 246, 291 Angiogram, 178, 246 Angiotensinogen, 246, 314 Animal model, 44, 55, 246 Anions, 243, 246, 285, 318, 322 Anomalies, 42, 246, 324 Anorexia, 29, 125, 168, 246 Anorexia Nervosa, 29, 125, 246 Anovulation, 46, 55, 246, 306 Antagonism, 246, 254 Antecedent, 10, 246 Antiandrogens, 155, 246, 251 Antibacterial, 246, 320 Antibiotic, 246, 253, 308, 320, 321 Antibodies, 5, 31, 33, 60, 61, 145, 246, 247, 278, 280, 290, 294, 306, 313 Anticoagulant, 247, 310 Anticonvulsant, 247, 257, 292 Antidepressant, 164, 247, 262 Antiemetic, 247, 266 Antifungal, 247, 286 Antigen, 15, 50, 58, 77, 91, 201, 243, 246, 247, 250, 260, 279, 280, 281, 282, 283, 291, 312, 317 Antihypertensive, 77, 111, 247 Anti-inflammatory, 241, 247, 262, 276, 282, 301 Antimicrobial, 247, 258 Antineoplastic, 243, 247, 262, 275, 292, 321 Antineoplastic Agents, 243, 247 Antioxidant, 28, 100, 112, 161, 168, 189, 247, 301 Antiproliferative, 153, 247 Antipyretic, 241, 247 Antiseptic, 247, 292 Antiserum, 247, 250 Antispasmodic, 247, 300, 316 Antiviral, 247, 284, 303 Anuria, 247, 286 Anus, 245, 247, 253, 303, 313 Anxiety, 26, 51, 132, 173, 186, 247, 301, 308, 309 Anxiolytic, 51, 247, 257, 293 Apnea, 7, 247 Apolipoproteins, 8, 248, 288 Apomorphine, 183, 248 Apoptosis, 8, 16, 35, 43, 45, 60, 93, 96, 100, 112, 122, 210, 248, 255 Applicability, 169, 248 Aqueous, 150, 152, 248, 250, 264, 269, 280, 287

Arachidonate 12-Lipoxygenase, 248, 289 Arachidonate 15-Lipoxygenase, 248, 289 Arachidonate Lipoxygenases, 248, 289 Arachidonic Acid, 248, 309 Arginine, 22, 154, 169, 174, 175, 195, 248, 297, 300, 312 Aromatase, 10, 17, 28, 52, 66, 105, 116, 133, 144, 170, 248 Aromatic, 67, 248, 266, 304 Arrhythmia, 94, 248 Arterial, 23, 90, 101, 151, 175, 177, 244, 248, 253, 257, 261, 281, 311, 323 Arteries, 178, 248, 249, 252, 262, 278, 289, 292, 295, 312, 328 Arteriolar, 248, 253, 314 Arterioles, 248, 249, 252, 254, 295 Ascites, 249, 299 Aseptic, 249, 321 Aspartic, 41, 249 Aspartic Acid, 41, 249 Assay, 21, 48, 68, 84, 92, 120, 249, 282, 312 Astrocytes, 249, 294 Asymptomatic, 172, 249, 277 Ataxia, 225, 249, 257, 324 Atenolol, 77, 111, 249 Atherogenic, 9, 249 ATP, 242, 249, 266, 275, 305, 310, 311, 326 Atrial, 249, 261, 327 Atrioventricular, 249, 262 Atrium, 249, 262, 324, 327, 330 Atrophy, 55, 140, 194, 225, 241, 249, 297 Atropine, 249, 316 Attenuated, 21, 159, 249, 266 Auditory, 249, 308, 329 Autoimmune disease, 249, 294 Autonomic, 241, 250, 298, 301, 303, 322 Autonomic Nervous System, 250, 301, 303, 322 Autopsy, 46, 250 Avian, 10, 64, 250 Avidity, 59, 250 Axillary, 166, 250 Axons, 62, 250, 296, 303 Azoospermia, 6, 89, 180, 250 B Bacteria, 246, 247, 250, 260, 264, 268, 269, 280, 292, 313, 320, 326, 329 Bacteriophage, 250, 305, 326 Bacteriostatic, 244, 250 Bacterium, 250, 260 Balloon Dilatation, 154, 250 Basal Ganglia, 249, 250, 253, 281, 288, 312

Index 335

Basal Ganglia Diseases, 249, 250, 281 Base, 18, 148, 241, 250, 264, 286, 304, 324 Basophil, 250, 279 Benign prostatic hyperplasia, 3, 15, 76, 78, 106, 147, 154, 155, 159, 181, 182, 193, 251, 273 Benign tumor, 251, 287 Benzene, 251, 256, 286 Benzodiazepines, 173, 251 Betahistine, 173, 251 Beta-pleated, 245, 251 Bicalutamide, 157, 251 Bilateral, 104, 154, 251, 306, 327 Bile, 251, 274, 276, 289, 321 Biliary, 250, 251, 254 Bilirubin, 243, 251, 276 Binding Sites, 35, 55, 172, 251 Bioavailability, 14, 83, 111, 165, 251 Bioavailable, 65, 72, 76, 80, 111, 138, 185, 251 Biochemical, 3, 5, 18, 19, 22, 26, 36, 102, 244, 251, 275, 286, 318 Biodegradation, 156, 176, 251 Biological response modifier, 251, 284 Biological therapy, 251, 278 Biomarkers, 50, 108, 251 Biosynthesis, 19, 55, 222, 248, 251, 300, 304, 328 Biotechnology, 64, 67, 122, 200, 209, 221, 224, 225, 226, 252 Biotransformation, 14, 15, 252 Bladder, 43, 154, 201, 251, 252, 263, 283, 294, 297, 310, 315, 328, 329, 331 Blister, 252, 302 Blood Coagulation, 252, 254, 325 Blood Platelets, 252, 318 Blood pressure, 8, 22, 151, 175, 208, 239, 247, 252, 255, 281, 294, 303, 312, 319 Blood Volume, 13, 252 Blood-Brain Barrier, 188, 252, 287 Blot, 53, 60, 63, 252, 282 Blotting, Western, 252, 282 Body Composition, 11, 18, 19, 44, 49, 58, 68, 69, 95, 96, 252 Body Fluids, 251, 252, 267, 306, 319, 327 Body Mass Index, 78, 192, 193, 252, 300 Bolus, 179, 252 Bolus infusion, 252 Bone Density, 29, 165, 252 Bone Marrow, 36, 87, 251, 253, 271, 282, 290, 294, 319, 322 Bone Resorption, 30, 210, 253

Boron, 114, 210, 253, 263 Boron Neutron Capture Therapy, 253 Bowel, 141, 245, 253, 265, 284, 285, 298, 321 Bowel Movement, 253, 265, 321 Brachytherapy, 253, 285, 286, 312, 331 Bradykinin, 253, 297, 306 Brain Hypoxia, 253, 324 Brain Infarction, 253 Brain Ischemia, 164, 253 Brain Stem, 253, 301 Branch, 237, 253, 263, 268, 278, 290, 302, 311, 320, 324 Breakdown, 19, 188, 253, 265, 275 Breast Neoplasms, 253, 274 Breeding, 157, 253 Broad-spectrum, 46, 253 Bronchi, 253, 270, 286, 326 Bronchial, 250, 251, 253, 279 Bronchodilator, 253, 286 Buccal, 16, 90, 207, 254, 290, 321 Bulbar, 100, 254 Bupivacaine, 254, 288 Burns, 136, 161, 189, 208, 254 Burns, Electric, 254 C Caffeine, 35, 53, 254 Calcium, 18, 34, 58, 106, 112, 166, 173, 210, 254, 259, 291, 319, 327 Calcium channel blocker, 173, 254 Calcium Channel Blockers, 173, 254 Calculi, 250, 254 Caloric intake, 139, 254 Cannula, 41, 254 Capillary, 253, 254, 255 Capillary Fragility, 254, 255 Capsid, 58, 254 Capsules, 149, 254, 267 Carbidopa, 188, 254 Carbohydrate, 31, 255, 262, 276, 307 Carbon Dioxide, 255, 264, 273, 275, 305, 315, 330 Carcinogen, 15, 255, 271 Carcinogenesis, 26, 93, 122, 255 Carcinogenic, 243, 251, 255, 284, 309, 321 Carcinoma, 39, 116, 147, 152, 169, 255, 263 Cardiac, 58, 73, 81, 102, 148, 161, 189, 244, 254, 255, 262, 270, 288, 293, 295, 321, 322 Cardiorespiratory, 255, 293 Cardioselective, 249, 255, 309 Cardiovascular disease, 22, 46, 177, 193, 255

336 Testosterone

Carotene, 20, 127, 255 Carrier Proteins, 255, 306, 312 Case report, 88, 107, 255, 258 Case-Control Studies, 50, 255, 270 Caspase, 85, 255 Castration, 13, 28, 78, 131, 154, 157, 185, 255 Catabolism, 32, 67, 208, 255 Catechin, 182, 255 Catecholamine, 255, 267 Catechols, 182, 256 Catheterization, 250, 256 Catheters, 250, 256, 283, 285 Caudal, 37, 59, 256, 265, 282, 307 Caudalis, 41, 256 Caudate Nucleus, 250, 256, 262, 296 Causal, 32, 256, 270 Cause of Death, 157, 256 Cell Adhesion, 66, 100, 256 Cell Cycle, 8, 52, 256, 263, 278 Cell Death, 36, 248, 256, 296 Cell Differentiation, 51, 256, 318 Cell Division, 210, 225, 250, 256, 263, 278, 291, 293, 305, 309, 317 Cell membrane, 254, 255, 256, 265, 272, 274, 305, 307 Cell proliferation, 8, 60, 256, 318 Cell Respiration, 242, 256, 293, 301, 315 Cell Survival, 35, 256, 278 Cellulose, 256, 305 Centrifugation, 256, 293 Cerebellar, 249, 257, 314, 327 Cerebellar Diseases, 249, 257, 327 Cerebrospinal, 140, 257, 309 Cerebrospinal fluid, 140, 257, 309 Cerebrovascular, 13, 250, 254, 255, 257, 324 Cerebrum, 257, 305, 327 Cervical, 59, 192, 257 Cervix, 257, 314 Chemoprevention, 5, 122, 257 Chemotherapy, 137, 168, 169, 257, 279 Chimeras, 36, 257 Chlordiazepoxide, 173, 257 Cholesterol Esters, 257, 288 Cholinergic, 173, 183, 257, 297 Chromaffin System, 257, 269 Chromatin, 248, 257, 270, 297, 320 Chromosomal, 194, 257, 275, 316 Chromosome, 24, 67, 68, 161, 189, 257, 260, 278, 288, 316, 317 Chronic Disease, 103, 211, 257, 259

Chronic renal, 257, 306 Chylomicrons, 258, 288 Ciliary, 258, 318 Ciliary Body, 258, 318 Ciprofloxacin, 64, 258 Circadian, 57, 155, 186, 258 Circadian Rhythm, 57, 155, 186, 258 Circulatory system, 144, 179, 258, 269 CIS, 36, 200, 258 Clamp, 29, 31, 33, 258 Climacteric, 70, 75, 90, 111, 159, 258 Clinical Medicine, 258, 307 Clinical study, 258, 261 Clinical trial, 4, 62, 68, 86, 135, 141, 221, 222, 258, 261, 267, 302, 311, 313 Clitoral, 169, 174, 175, 183, 258 Clomiphene, 71, 74, 258 Clonic, 258, 292 Cloning, 64, 252, 258 Coca, 258, 259 Cocaine, 12, 13, 24, 79, 258, 259 Cod Liver Oil, 259, 269 Cofactor, 259, 311, 325 Cognition, 58, 105, 186, 259 Cohort Studies, 259, 270 Colitis, 259, 284 Collagen, 255, 259, 272, 273, 280, 290, 306 Collagen disease, 259, 280 Collapse, 253, 259, 319 Colloidal, 243, 259, 268, 304, 318, 322 Combination Therapy, 87, 88, 112, 259, 271 Comorbidity, 92, 259 Complement, 259, 260, 306, 317 Complementary and alternative medicine, 115, 129, 260 Complementary medicine, 115, 260 Computational Biology, 221, 224, 260 Conception, 260, 261, 273, 319, 321 Concomitant, 140, 158, 171, 260 Condoms, 192, 260 Confounding, 11, 48, 260 Conjugated, 173, 260, 263, 298 Conjugation, 73, 252, 260 Conjunctiva, 261, 327 Conjunctivitis, 261, 324 Connective Tissue, 194, 253, 259, 261, 273, 274, 290, 303, 315 Connective Tissue Cells, 261 Consciousness, 245, 261, 264, 266 Constitutional, 5, 81, 261 Constriction, 197, 261, 286, 316, 329

Index 337

Constriction, Pathologic, 261, 329 Consumption, 16, 19, 32, 185, 261, 265, 298, 301 Continuum, 51, 261 Contraception, 27, 40, 68, 85, 86, 96, 110, 180, 190, 192, 208, 261, 287 Contraceptive, 68, 105, 167, 174, 175, 180, 192, 261, 265, 269, 291, 298 Contraceptive Agents, 167, 261, 265 Contraindications, ii, 138, 261 Control group, 261, 308, 313 Controlled clinical trial, 49, 50, 261 Controlled study, 63, 139, 261 Convalescence, 136, 261 Convulsions, 247, 261, 268, 308 Coordination, 155, 261, 294 Cor, 5, 56, 261 Coronary, 103, 112, 118, 177, 178, 255, 262, 292, 295 Coronary Arteriosclerosis, 262, 295 Coronary heart disease, 255, 262 Coronary Thrombosis, 262, 292, 295 Corpus, 52, 118, 188, 262, 276, 290, 296, 302, 305, 309, 318, 325 Corpus Luteum, 262, 290, 309 Corpus Striatum, 188, 262, 276, 296 Cortex, 190, 191, 249, 262, 271, 273, 285, 308, 314 Cortical, 22, 262, 308, 317, 324 Corticosteroid, 262, 308 Cortisol, 45, 48, 64, 70, 78, 87, 91, 102, 111, 119, 123, 132, 160, 198, 243, 262 Cotinine, 48, 262 Coumarin, 263 Coumestrol, 120, 263 Courtship, 67, 263 Cranial, 263, 272, 278, 296, 301, 303, 327, 329 Crossing-over, 263, 313 Cross-Sectional Studies, 263, 270 Cryptorchidism, 42, 94, 194, 263 Crystallization, 55, 263 Cues, 40, 263 Curative, 263, 324 Curcumin, 182, 263 Cutaneous, 36, 263, 277, 287, 290 Cyclic, 24, 43, 52, 158, 171, 242, 254, 263, 278, 297, 304, 310 Cyclin, 8, 66, 263 Cyproterone, 263, 274 Cystitis, 43, 172, 263

Cytochrome, 14, 32, 34, 39, 84, 102, 118, 120, 145, 248, 263 Cytogenetics, 263, 316 Cytokine, 31, 58, 61, 77, 263 Cytoplasm, 248, 256, 264, 270, 272, 277, 294, 297, 323 Cytoskeleton, 105, 264 Cytotoxic, 264, 313, 319 D Dairy Products, 210, 264 Danazol, 172, 264 Data Collection, 8, 26, 50, 264 Databases, Bibliographic, 221, 264 Deamination, 264, 294, 328 Decarboxylation, 264, 279, 300, 312 Decubitus, 163, 264 Deletion, 26, 38, 52, 55, 248, 264 Dementia, 58, 76, 264 Dendrites, 264, 297, 299 Density, 8, 12, 18, 30, 71, 72, 73, 85, 210, 252, 257, 264, 267, 288, 299 Dental Caries, 264, 274 Deoxyribonucleotides, 146, 264, 275, 299 Depolarization, 265, 319 Dermal, 88, 193, 265 Dermatitis, 265, 316 Desogestrel, 85, 89, 265 Detoxification, 265, 276 Deuterium, 265, 280 Developed Countries, 149, 265 Dextroamphetamine, 245, 265 DHEA, 18, 19, 44, 88, 112, 117, 127, 147, 150, 174, 175, 179, 195, 222, 264, 265 Diabetes Mellitus, 19, 22, 89, 160, 265, 276, 278, 298 Diagnostic procedure, 143, 209, 265 Diastole, 265 Diastolic, 160, 265, 281 Diathermy, 265, 293 Diencephalon, 265, 282, 308, 324, 325 Dietary Fats, 265, 288 Diffusion, 265, 266 Digestion, 243, 251, 253, 265, 285, 288, 289, 303, 321, 329 Digestive system, 142, 265 Digestive tract, 265, 319 Dilator, 173, 266 Dilution, 100, 155, 176, 266, 270, 306 Diploid, 266, 305 Direct, iii, 10, 25, 29, 30, 58, 147, 150, 165, 185, 194, 213, 258, 266, 267, 295, 314, 323 Discrimination, 13, 266

338 Testosterone

Disinfectant, 266, 292 Disposition, 38, 49, 81, 84, 178, 266 Dissection, 266, 327 Dissociation, 156, 176, 243, 266 Dissociative Disorders, 266 Distal, 266, 303, 311 Diuresis, 254, 266 Diuretic, 164, 266 Diurnal, 76, 97, 155, 266 DNA Topoisomerase, 266, 275 Docetaxel, 137, 266 Dominance, 53, 94, 99, 266 Domperidone, 189, 266 Dopa, 188, 254, 266, 287 Dopa Decarboxylase, 188, 254, 266 Dopamine, 24, 151, 155, 175, 188, 245, 248, 254, 259, 265, 266, 267, 287, 294, 304 Dopamine Agonists, 188, 267 Dorsal, 41, 118, 267, 307, 321 Dorsum, 267 Dosage Forms, 149, 151, 175, 267 Dose-dependent, 99, 267 Double-blinded, 49, 267 Drive, ii, vi, 55, 109, 172, 197, 207, 211, 267, 288 Drug Delivery Systems, 148, 267 Drug Interactions, 32, 34, 215, 267 Drug Tolerance, 267, 325 Duct, 254, 256, 267, 316, 322, 329 Dyes, 156, 176, 245, 267, 297 Dyslipidemia, 19, 267 Dyspareunia, 172, 183, 267, 271 Dysplasia, 28, 120, 225, 268 Dystrophin, 268, 295 Dystrophy, 225, 268 E Eclampsia, 268, 308 Edema, 6, 165, 268, 299, 308 Effector, 35, 59, 241, 259, 268, 297, 304 Effector cell, 59, 268, 297 Efficacy, 3, 9, 11, 12, 20, 33, 50, 52, 62, 68, 138, 139, 149, 153, 180, 268, 327 Ejaculation, 69, 154, 158, 268, 317 Elective, 268 Electrocardiogram, 76, 268 Electrolyte, 262, 268, 286, 293, 307, 319 Electrons, 247, 250, 268, 285, 301, 312, 313 Electrophoresis, 244, 268, 274 Electrophysiological, 41, 268 Embolus, 268, 283 Embryo, 119, 164, 256, 268, 273, 283, 299, 328

Emetic, 188, 248, 268 Emollient, 268, 299 Empirical, 53, 57, 268 Emulsion, 156, 176, 269, 273 Enanthate, 11, 63, 124, 139, 141, 180, 184, 191, 192, 196, 269 Encapsulated, 156, 176, 269 Endocrine Glands, 269 Endocrine System, 9, 269, 297 Endocrinologist, 9, 269 Endometrial, 153, 164, 269 Endometriosis, 33, 147, 152, 153, 181, 264, 269, 287, 298 Endometrium, 92, 164, 210, 269, 292 Endorphin, 156, 269 Endoscopic, 269, 282, 293 Endothelial cell, 10, 66, 79, 97, 100, 252, 269, 325 Endothelium, 269, 297 Endothelium-derived, 269, 297 Endotoxin, 269, 328 End-stage renal, 257, 269, 306 Energy balance, 269, 287, 305 Enhancer, 148, 177, 192, 193, 269 Enterovirus, 58, 269 Environmental Exposure, 270, 299 Environmental Health, 220, 222, 270 Enzymatic, 254, 255, 260, 264, 270, 273, 279 Enzyme, 3, 4, 19, 28, 52, 64, 138, 145, 159, 178, 191, 192, 242, 248, 255, 266, 268, 270, 277, 278, 286, 288, 289, 292, 294, 304, 306, 310, 311, 314, 318, 322, 325, 326, 330, 331 Eosinophils, 270, 277, 287 Epidemiologic Studies, 20, 39, 270 Epidemiological, 50, 270 Epidermis, 241, 252, 270, 302 Epinephrine, 242, 267, 270, 286, 298, 328 Epiphyseal, 166, 270 Epitestosterone, 73, 75, 78, 94, 116, 270 Epithelial, 26, 98, 242, 258, 270 Epithelial Cells, 26, 98, 270 Epithelium, 10, 26, 269, 270, 310, 317 Epitope, 145, 270 Erection, 52, 151, 169, 175, 197, 270, 308 Erythrocyte Volume, 252, 270 Erythrocytes, 246, 253, 270, 314, 317 Erythropoiesis, 190, 270 Erythropoietin, 166, 271 Escalation, 26, 271 Esophagus, 265, 271, 304, 321, 329 Essential Tremor, 225, 271

Index 339

Estriol, 60, 271 Estrogen receptor, 10, 28, 42, 54, 56, 118, 258, 271 Estrogen Replacement Therapy, 4, 70, 271 Estrone, 147, 271 Ethinyl Estradiol, 118, 173, 271 Ethisterone, 172, 271 Ethnic Groups, 5, 38, 271 Eukaryotic Cells, 271, 283, 300, 328 Evoke, 271, 321 Excipient, 149, 271 Excrete, 247, 271, 286 Exercise Test, 271, 272 Exercise Tolerance, 63, 272 Exocytosis, 272, 279, 323 Exogenous, 23, 81, 153, 166, 168, 179, 185, 252, 272, 275, 276, 310, 328 Exons, 37, 272 Expiration, 272, 315 External-beam radiation, 272, 285, 312, 331 Extracellular, 245, 249, 261, 272, 273, 291, 300, 319 Extracellular Matrix, 261, 272, 273, 291, 300 Extracellular Matrix Proteins, 272, 291 Extraction, 14, 120, 272 Extraocular, 242, 272 Extrapyramidal, 267, 272 F Facial, 41, 53, 60, 166, 170, 178, 184, 272, 330 Facial Nerve, 60, 272 Fallopian Tubes, 272, 314 Family Planning, 40, 192, 221, 272 Fathers, 87, 98, 272 Fatigue, 168, 272, 278, 295 Fatty acids, 77, 182, 243, 273, 289, 309 Febrile, 21, 273 Femoral, 115, 273 Femur, 273 Fentanyl, 193, 273 Fetal Development, 194, 273 Fetus, 164, 271, 273, 274, 305, 308, 328, 329 Fibrin, 252, 273, 325 Fibrinolytic, 72, 273 Fibroblasts, 63, 80, 101, 261, 273, 285 Fibroid, 273, 287 Fibrosis, 31, 225, 244, 273, 316 Finasteride, 3, 30, 78, 182, 273 Fissure, 273, 308 Fistula, 273, 298, 323

Fixation, 273, 317 Flatus, 273, 275 Flexor, 273, 320 Fluorescence, 62, 273 Fluorine, 159, 274 Fluoxymesterone, 165, 274 Flutamide, 30, 61, 274 Foetoplacental, 274, 299 Fold, 39, 273, 274 Follicles, 43, 145, 179, 274, 284 Follicular Phase, 159, 274 Forearm, 252, 274 Frail Elderly, 97, 138, 274 Friction, 274, 289 Frontal Lobe, 274, 308 Frostbite, 274, 304 Fungi, 247, 260, 274, 292, 321, 331 G Galanin, 40, 274 Gallbladder, 241, 251, 265, 274 Gallic Acid, 161, 190, 274 Gamma Rays, 274, 312, 313 Gamma-Globulins, 105, 274 Ganglia, 59, 241, 250, 274, 296, 301, 303, 322 Gangliosides, 64, 274 Gap Junctions, 274, 323 Gas, 100, 245, 255, 265, 273, 274, 275, 280, 297, 298, 322, 329, 330 Gas exchange, 275, 330 Gastric, 250, 267, 275, 279, 303 Gastrin, 275, 280 Gastrointestinal, 14, 196, 210, 253, 258, 266, 270, 273, 275, 287, 318, 320, 322, 327 Gastrointestinal tract, 196, 210, 273, 275, 287, 318, 320, 327 Gels, 150, 192, 275 Gene Expression, 15, 36, 37, 41, 43, 61, 95, 226, 275 Gene Targeting, 42, 275 Genetic Techniques, 14, 275 Genetic transcription, 275, 309, 326 Genetics, 19, 112, 210, 260, 263, 266, 275 Genistein, 118, 120, 275 Genital, 42, 49, 150, 230, 258, 275, 329 Genitourinary, 275, 329 Genomics, 9, 275 Genotype, 25, 32, 38, 50, 275, 304 Geriatric, 71, 74, 97, 168, 275 Geriatric Assessment, 97, 275 Germ Cells, 275, 291, 299, 300, 319, 320, 324

340 Testosterone

Gestation, 275, 303, 305 Gestational, 42, 275 Gestational Age, 42, 275 Ginkgo biloba, 32, 154, 276 Ginseng, 32, 78, 111, 119, 128, 154, 276 Gland, 155, 181, 190, 191, 242, 257, 276, 279, 281, 288, 290, 301, 305, 310, 316, 317, 321, 322, 325 Globus Pallidus, 250, 262, 276, 312 Glomerular, 23, 30, 276, 286 Glomerulus, 276 Glucocorticoid, 37, 57, 184, 185, 210, 276, 280, 308 Gluconeogenesis, 31, 276 Glucose, 18, 22, 31, 32, 56, 82, 100, 116, 148, 160, 177, 225, 256, 265, 276, 277, 278, 284, 316 Glucose Intolerance, 265, 276 Glucose tolerance, 31, 32, 56, 100, 276 Glucose Tolerance Test, 100, 276 Glucuronic Acid, 276, 328 Glucuronides, 92, 276 Glutamic Acid, 276, 306 Glutathione Peroxidase, 277, 317 Glycogen, 66, 277, 295 Glycogen Synthase, 66, 277 Glycoprotein, 105, 271, 277, 318, 325, 327 Goats, 264, 277 Gonad, 5, 277 Gonadorelin, 277, 287 Gonadotropic, 146, 277 Gonadotropin, 5, 25, 27, 33, 37, 40, 49, 82, 83, 94, 133, 149, 214, 277, 287 Gonorrhoea, 277, 300 Governing Board, 277, 307 Gp120, 277, 303 Grade, 50, 277, 310 Graft, 277, 280, 283 Graft Rejection, 277, 283 Grafting, 277, 283 Granulocytes, 60, 250, 277, 319, 331 Granulosa Cells, 278, 284, 290 Growth factors, 35, 60, 278 Guanylate Cyclase, 278, 297 H Haematological, 87, 112, 278 Haematology, 278 Half-Life, 188, 278 Handedness, 93, 278 Haploid, 278, 305 Haptens, 243, 278, 312 Headache, 254, 278, 309, 329

Heart attack, 255, 278 Heart failure, 69, 278, 299 Heart Valves, 250, 278 Heartbeat, 278, 322, 330 Helix-loop-helix, 37, 278 Heme, 251, 263, 278 Hemodialysis, 278, 286 Hemoglobin, 246, 270, 278, 279, 287 Hemoglobinuria, 225, 279 Hemorrhage, 278, 279, 321 Hemostasis, 279, 318 Hepatic, 14, 31, 97, 118, 243, 276, 279, 294 Hepatocyte, 15, 279 Hereditary, 101, 178, 279, 296, 306, 315 Heredity, 275, 279 Herpes, 163, 279 Herpes Zoster, 279 Heterogeneity, 243, 279 Heterotropic, 34, 279 Heterozygotes, 266, 279 Hidradenitis, 182, 279 Hirsutism, 46, 147, 159, 182, 263, 279, 281 Histamine, 161, 189, 251, 279, 324 Histamine Release, 161, 189, 279 Histidine, 279 Histology, 26, 279, 301 Homeostasis, 158, 171, 279, 301 Homogeneous, 261, 279, 304 Homologous, 244, 263, 275, 279, 280, 294, 317, 323 Homozygotes, 266, 280 Hormonal therapy, 84, 156, 176, 190, 280 Hormone Replacement Therapy, 7, 10, 57, 153, 164, 165, 191, 192, 201, 280 Hormone therapy, 137, 148, 178, 190, 191, 280, 291 Host, 21, 33, 59, 169, 186, 250, 280, 282, 283, 330 Human growth hormone, 160, 178, 280, 320 Hybrid, 167, 280 Hybridization, 6, 41, 280 Hybridomas, 280, 285 Hydrocortisone, 112, 121, 280 Hydrogel, 148, 280 Hydrogen Peroxide, 277, 280, 288, 322 Hydrolysis, 249, 252, 280, 304, 307 Hydrophilic, 280 Hydrophobic, 280, 288 Hydroxylation, 105, 106, 145, 281 Hyperandrogenism, 22, 281 Hypercholesterolemia, 193, 267, 281

Index 341

Hyperglycemia, 31, 281 Hyperlipidemia, 267, 281 Hyperplasia, 52, 92, 281 Hypersecretion, 82, 281, 316 Hypersensitivity, 244, 281, 315, 317 Hypertension, 19, 23, 91, 95, 160, 169, 254, 255, 278, 281, 298, 304, 308, 309 Hyperthermia, 154, 265, 281 Hypertrichosis, 279, 281 Hypertriglyceridemia, 267, 281 Hypertrophy, 30, 63, 102, 103, 144, 152, 154, 162, 170, 187, 251, 262, 281, 327 Hypnotic, 281, 293 Hypoglycemia, 162, 281 Hypogonadism, 17, 33, 38, 72, 73, 74, 82, 107, 140, 165, 172, 185, 193, 201, 274, 281 Hypokinesia, 188, 281, 302 Hypolipidemic, 55, 281 Hypophysis, 147, 281, 317 Hypospadias, 42, 102, 108, 281 Hypothalamic, 6, 33, 37, 57, 69, 131, 133, 140, 170, 187, 281 Hypothyroidism, 86, 282 Hypoxia, 7, 282 Hysteroscopy, 152, 282 I Ibuprofen, 156, 176, 282 Id, 113, 124, 178, 231, 236, 238, 282 Idiopathic, 6, 78, 279, 282, 324 Immune adjuvant, 33, 282 Immune response, 33, 36, 59, 242, 247, 249, 262, 277, 278, 282, 283, 317, 322, 330 Immune system, 21, 251, 268, 282, 283, 290, 294, 329, 331 Immunity, 36, 282 Immunization, 282, 283, 308, 317 Immunoassay, 82, 282 Immunoblotting, 31, 282 Immunodeficiency, 92, 225, 282 Immunogenic, 282, 312 Immunoglobulin, 58, 246, 272, 282, 294 Immunologic, 276, 282, 313 Immunology, 101, 242, 243, 282 Immunosuppressant, 243, 282 Immunosuppressive, 6, 276, 283 Immunosuppressive therapy, 6, 283 Immunotherapy, 33, 251, 283 Impairment, 21, 23, 28, 58, 138, 162, 249, 283, 292 Implant radiation, 283, 285, 312, 331 Implantation, 45, 119, 260, 283, 299

Impotence, 48, 52, 74, 85, 125, 168, 197, 230, 270, 283, 304, 309, 331 In situ, 59, 61, 283 In Situ Hybridization, 59, 61, 283 In vivo, 6, 24, 26, 34, 36, 55, 59, 63, 65, 111, 121, 122, 145, 153, 172, 283 Incision, 283, 285, 310, 315 Incontinence, 154, 283, 316 Incubated, 7, 283 Indicative, 198, 283, 302, 329 Induction, 10, 28, 31, 32, 33, 36, 54, 68, 122, 145, 190, 191, 245, 265, 283, 309, 330 Infancy, 194, 283 Infarction, 160, 253, 283 Infertility, 6, 34, 37, 55, 61, 125, 173, 185, 194, 283 Inflammation, 63, 161, 189, 241, 243, 244, 247, 258, 259, 261, 263, 265, 273, 279, 280, 284, 295, 300, 315, 321 Inflammatory bowel disease, 71, 284 Infusion, 17, 123, 284 Ingestion, 32, 76, 78, 111, 119, 276, 284, 306 Inhalation, 173, 174, 242, 284, 306 Inhibin, 25, 37, 84, 94, 108, 284 Initiation, 26, 37, 47, 77, 169, 188, 210, 284, 309, 326 Inlay, 284, 315 Innervation, 272, 284 Inotropic, 249, 267, 284 Insight, 19, 24, 284 Insomnia, 57, 284, 301 Insulator, 284, 294 Insulin-dependent diabetes mellitus, 284 Insulin-like, 49, 50, 60, 65, 78, 111, 116, 119, 284 Interferon, 58, 65, 88, 284 Interferon-alpha, 284 Interleukin-1, 21, 110, 284 Interleukin-2, 285 Interleukin-6, 79, 101, 285 Intermittent, 7, 181, 285, 289 Internal Capsule, 262, 285 Internal radiation, 285, 312, 331 Interstitial, 43, 119, 172, 175, 253, 285, 286, 288, 331 Intestinal, 18, 255, 269, 276, 285, 290 Intestine, 188, 253, 285, 286, 304 Intoxication, 285, 331 Intramuscular, 11, 81, 107, 285, 302 Intramuscular injection, 11, 285 Intraperitoneal, 123, 285

342 Testosterone

Intravenous, 12, 13, 14, 31, 79, 118, 284, 285, 302 Intrinsic, 243, 285 Introns, 37, 285 Invasive, 38, 50, 145, 154, 173, 179, 282, 285, 310 Involuntary, 9, 150, 173, 250, 271, 285, 295, 314, 320 Ionizing, 244, 270, 285, 313 Ions, 250, 266, 268, 280, 285, 307 Irradiation, 6, 163, 253, 285, 331 Ischemia, 162, 249, 253, 274, 286 Isoflavones, 122, 286 Isopropyl, 195, 286 Isoproterenol, 5, 286 Isozymes, 19, 182, 286 J Joint, 41, 172, 258, 273, 286, 323 K Kb, 37, 220, 286 Keto, 126, 286 Ketoconazole, 160, 286 Kidney Disease, 30, 139, 142, 220, 225, 286 Kidney Failure, 31, 269, 286 Kidney Failure, Acute, 286 Kidney Failure, Chronic, 286 Kinetic, 34, 285, 286 L Lacrimal, 242, 272, 286 Lacrimal Apparatus, 242, 286 Lactation, 286, 299, 301, 309 Lag, 50, 286 Large Intestine, 265, 285, 286, 313, 319 Laryngeal, 166, 287 Larynx, 287, 326, 329, 331 Latent, 46, 287, 307 Least-Squares Analysis, 287, 314 Leiomyoma, 33, 273, 287 Leishmaniasis, 36, 287 Lens, 184, 287 Leptin, 68, 79, 97, 123, 287 Lesion, 6, 287, 289 Lethal, 43, 287 Lethargy, 170, 187, 195, 282, 287 Leucine, 31, 287 Leukemia, 225, 287 Leukocytes, 39, 253, 270, 277, 284, 287, 294, 297, 328 Leuprolide, 69, 94, 107, 137, 140, 141, 214, 287 Levo, 266, 287, 298 Levodopa, 188, 254, 266, 287

Levonorgestrel, 86, 105, 287, 298 Leydig Cells, 65, 88, 288 Library Services, 236, 288 Lidocaine, 14, 288 Ligament, 288, 310 Likelihood Functions, 288, 314 Limbic, 288, 308 Limbic System, 288, 308 Linear Models, 288, 314 Linkages, 278, 288, 299 Lipase, 97, 288 Lipid, 8, 55, 156, 176, 193, 248, 284, 286, 288, 293, 294, 301, 327 Lipid Peroxidation, 288, 301 Lipophilic, 14, 34, 288 Lipopolysaccharide, 21, 288 Lipoprotein, 8, 76, 83, 85, 111, 267, 288, 289 Liposomes, 156, 176, 288 Lipoxygenase, 115, 248, 289 Litter, 45, 289 Litter Size, 45, 289 Lobe, 280, 289 Localization, 65, 121, 289 Localized, 42, 54, 91, 253, 264, 268, 269, 273, 279, 281, 283, 289, 294, 299, 305, 329 Locomotion, 289, 305 Locomotor, 13, 24, 289 Logistic Models, 289, 314 Longitudinal study, 42, 289 Long-Term Care, 138, 289 Loop, 289 Low-density lipoprotein, 267, 288, 289 Lubricants, 289, 304 Lubrication, 183, 289 Lumen, 254, 290 Lupus, 126, 211, 259, 290 Lutein Cells, 290, 309 Luteinizing hormone-releasing hormone agonist, 81, 82, 111, 181, 290 Lycopene, 16, 290 Lymph, 250, 257, 258, 269, 290 Lymph node, 250, 257, 290 Lymphatic, 269, 283, 290, 299, 319, 325 Lymphatic system, 290, 319, 325 Lymphocyte, 58, 247, 290, 291 Lymphoid, 59, 246, 290 Lymphoma, 225, 290 M Macrophage, 34, 285, 290 Malabsorption, 225, 290 Malignancy, 39, 290

Index 343

Malignant, 36, 225, 242, 247, 290, 296, 313, 324 Malnutrition, 243, 249, 290, 295 Mammary, 290, 324 Mammogram, 12, 290 Mandible, 244, 290, 315 Manifest, 35, 290 Mastication, 290, 327 Matrix metalloproteinase, 10, 290 Medial, 56, 59, 276, 291, 300 Mediate, 9, 24, 36, 40, 267, 291 Mediator, 191, 192, 266, 285, 291, 318 Medical Staff, 267, 291 Medicament, 151, 175, 188, 244, 291 MEDLINE, 221, 224, 225, 291 Medroxyprogesterone, 66, 124, 291 Medroxyprogesterone Acetate, 66, 124, 291 Medullary, 22, 41, 291, 312 Megestrol, 63, 79, 87, 139, 291 Megestrol Acetate, 63, 79, 139, 291 Meiosis, 291, 294, 323 Melanin, 40, 291, 304, 328 Melanocytes, 291 Melanoma, 225, 253, 291 Membrane Glycoproteins, 291 Membrane Proteins, 289, 291 Memory, 86, 160, 161, 162, 186, 189, 205, 207, 246, 264, 291 Meninges, 256, 292 Menopause, 70, 73, 75, 85, 88, 90, 96, 107, 112, 126, 158, 164, 167, 168, 172, 185, 193, 199, 201, 292, 299, 303, 307, 308, 309 Menstrual Cycle, 13, 22, 55, 132, 145, 159, 179, 274, 292, 299, 309 Menstruation, 244, 274, 292, 299 Mental Disorders, 142, 281, 292, 308, 311 Mental Health, iv, 4, 140, 142, 220, 223, 292, 308, 311 Mental Processes, 266, 292, 311 Menthol, 169, 175, 292 Mephenytoin, 32, 292 Mercuric Chloride, 45, 292 Meta-Analysis, 101, 112, 292 Metabolic disorder, 33, 55, 292 Metabolite, 8, 48, 54, 80, 158, 159, 166, 171, 182, 252, 271, 292, 308 Metastasis, 35, 291, 292 Metastasize, 28, 292, 317 Metastatic, 28, 35, 86, 137, 144, 187, 292, 317 Methyltestosterone, 74, 80, 127, 165, 292

MI, 78, 103, 122, 177, 240, 292 Microbe, 292, 326 Microorganism, 259, 292, 302, 330 Microscopy, 55, 62, 292 Microsomal, 84, 293 Microwaves, 154, 293, 312 Midazolam, 14, 35, 120, 293 Migration, 244, 293 Milliliter, 252, 293 Mineralocorticoids, 242, 262, 293 Mitochondria, 34, 293, 300 Mitosis, 51, 248, 293 Mitotic, 52, 62, 266, 293 Mitotic inhibitors, 266, 293 Mobility, 274, 293 Modeling, 26, 55, 293 Modification, 15, 46, 47, 293, 312 Modulator, 190, 191, 293 Molecular Conformation, 33, 293 Molecular mass, 152, 293 Monitor, 35, 293, 298 Monoamine, 188, 245, 265, 294, 328 Monoamine Oxidase, 188, 245, 265, 294, 328 Monoclonal, 37, 145, 280, 282, 286, 294, 312, 331 Monoclonal antibodies, 145, 282, 294 Monocytes, 284, 285, 287, 294 Mononuclear, 294, 328 Monophosphate, 158, 171, 294 Monotherapy, 108, 294 Mood Disorders, 21, 294 Morphine, 42, 248, 294, 296, 300 Morphological, 6, 243, 268, 291, 294 Morphology, 45, 62, 161, 189, 278, 294 Motility, 45, 294, 318 Motion Sickness, 294, 296, 316 Mucins, 294, 316 Mucocutaneous, 287, 294 Mucosa, 14, 163, 290, 294, 296, 309, 321 Multiple sclerosis, 162, 294 Multivalent, 250, 294 Muscle Fatigue, 161, 189, 295 Muscle Fibers, 295, 327 Muscle Proteins, 29, 295 Muscular Atrophy, 100, 136, 140, 225, 295 Muscular Dystrophies, 268, 295 Musculature, 166, 281, 295 Mutagenesis, 35, 55, 295 Mutagenic, 243, 295 Mutagens, 295 Mydriatic, 295, 316, 331

344 Testosterone

Myelin, 62, 294, 295 Myocardial infarction, 72, 160, 177, 262, 292, 295, 309 Myocardial Ischemia, 118, 295 Myocarditis, 58, 295 Myocardium, 58, 292, 295 Myosin, 29, 295, 327 Myotonic Dystrophy, 97, 225, 295 N Naloxone, 156, 157, 295 Narcotic, 273, 294, 296 Nasal Cavity, 296, 331 Nasal Septum, 296, 331 Nausea, 189, 247, 267, 296, 328 NCI, 1, 137, 141, 219, 258, 296 Necrosis, 248, 253, 283, 292, 295, 296 Neonatal, 22, 23, 54, 60, 121, 277, 296 Neonatal period, 23, 296 Neoplasia, 50, 162, 225, 296, 310 Neoplasm, 296, 328 Neoplastic, 245, 280, 290, 296 Neostriatum, 256, 262, 296, 312 Nephron, 23, 276, 296 Nephropathy, 30, 286, 296 Nerve Fibers, 118, 296 Nerve Regeneration, 60, 296 Neural, 5, 21, 24, 54, 242, 245, 294, 296, 303 Neuralgia, 41, 296 Neurodegenerative Diseases, 162, 250, 296 Neuroendocrine, 21, 56, 59, 160, 297 Neurogenic, 10, 151, 154, 175, 297 Neurologic, 140, 297 Neuronal, 4, 10, 38, 60, 62, 66, 162, 297, 303 Neuronal Plasticity, 62, 297 Neurons, 4, 5, 10, 37, 40, 41, 56, 59, 62, 66, 161, 188, 259, 264, 274, 287, 296, 297, 322, 323 Neuropathy, 297, 303 Neuropeptide, 37, 56, 297 Neurosecretory Systems, 269, 297 Neurotransmitters, 294, 297 Neutrons, 244, 253, 285, 297, 312 Neutrophils, 248, 277, 287, 297 Nicotine, 48, 193, 297 Nitric Oxide, 22, 31, 52, 88, 117, 154, 183, 297 Nitrogen, 73, 166, 243, 244, 245, 272, 273, 286, 293, 298, 327 Norepinephrine, 22, 242, 267, 298 Norgestrel, 287, 298

Nuclear, 15, 16, 34, 112, 121, 122, 124, 250, 260, 268, 271, 274, 285, 288, 296, 298, 310, 324 Nuclear Proteins, 15, 298 Nuclei, 7, 59, 62, 63, 244, 260, 268, 272, 285, 288, 293, 297, 298, 301, 311 Nucleic acid, 254, 280, 283, 295, 298, 320 Nucleic Acid Hybridization, 280, 298 Nucleoproteins, 298 Nutritional Status, 16, 87, 298 O Observational study, 49, 298 Occult, 35, 298 Octreotide, 56, 298 Odour, 248, 298 Oedema, 162, 298 Oestradiol, 112, 299 Oestrogen, 88, 153, 299 Ointments, 192, 267, 299, 301 Olfactory Bulb, 299, 331 Oligodeoxyribonucleotides, 146, 299 Oligomenorrhea, 299, 306 Oligoribonucleotides, 146, 299 Oliguria, 286, 299 Oncogene, 225, 299 On-line, 75, 239, 299 Oocytes, 37, 299 Oophorectomy, 153, 299, 322 Opacity, 264, 299 Operon, 299, 309 Opium, 294, 299 Optic Chiasm, 282, 300, 308 Oral Health, 300 Oral Hygiene, 163, 300 Orchiectomy, 23, 154, 300, 322 Orchitis, 194, 300 Organelles, 52, 256, 264, 291, 294, 300, 306 Orgasm, 145, 150, 169, 179, 183, 268, 300 Ornithine, 122, 300, 312 Ornithine Decarboxylase, 122, 300 Orthostatic, 298, 300 Osmotic, 243, 300, 318 Osteoblasts, 10, 17, 300 Osteoporosis, 10, 17, 18, 29, 126, 153, 162, 164, 165, 190, 193, 210, 271, 299, 300 Ovarian Cysts, 110, 300 Ovariectomy, 13, 23, 300 Ovaries, 21, 43, 44, 140, 147, 158, 164, 175, 248, 272, 281, 299, 300, 306, 314, 318, 322 Ovary, 25, 55, 84, 110, 158, 171, 246, 262, 271, 277, 299, 300, 301 Overweight, 46, 82, 113, 210, 300

Index 345

Ovulation, 43, 46, 55, 145, 164, 179, 246, 258, 274, 278, 291, 298, 300, 301 Ovum, 262, 275, 301, 309, 331 Oxazepam, 155, 301 Oxidation, 19, 161, 189, 241, 247, 248, 252, 263, 277, 288, 301 Oxidation-Reduction, 252, 301 Oxidative metabolism, 14, 242, 301 Oxidative Stress, 30, 75, 118, 301 Oxygen Consumption, 271, 301, 315 Oxytocin, 44, 56, 195, 301 P Palate, 301, 321 Palliative, 263, 291, 299, 301, 324 Palpitation, 168, 301 Pancreas, 241, 251, 265, 284, 288, 301, 320, 327 Pancreatic, 225, 301 Pancreatic cancer, 225, 301 Papilla, 88, 301 Paraffin, 15, 301 Paralysis, 254, 301 Parasympathetic Nervous System, 183, 301 Parenchyma, 10, 302 Parent-Child Relations, 97, 302 Parenteral, 29, 102, 108, 149, 302 Parkinsonism, 248, 254, 287, 302 Paroxysmal, 225, 302, 329 Particle, 302, 326 Parturition, 302, 309 Patch, 139, 206, 208, 302, 326 Pathogen, 21, 302 Pathogenesis, 29, 210, 302 Pathologic, 248, 262, 281, 302, 315 Pathologic Processes, 248, 302 Pathophysiology, 31, 46, 200, 302 Patient Compliance, 33, 302 Patient Education, 230, 234, 236, 240, 302 Patient Selection, 230, 302 Peer Review, 109, 174, 302 Pelvic, 43, 173, 183, 269, 302, 310 Pemphigus, 211, 241, 302 Penile Erection, 169, 302 Penis, 117, 151, 166, 169, 175, 260, 268, 281, 302, 308, 314 Peptic, 251, 303 Peptic Ulcer, 251, 303 Peptide, 4, 33, 38, 40, 56, 117, 145, 147, 149, 152, 287, 303, 306, 307, 310, 311, 325 Peptide T, 33, 303, 306 Perception, 80, 111, 303, 316

Perfusion, 102, 123, 282, 303, 325 Perimenopausal, 57, 303 Perinatal, 12, 23, 48, 54, 60, 303 Perineal, 303, 312 Perineum, 151, 175, 281, 303 Periodicity, 303, 315 Peripheral blood, 15, 284, 303 Peripheral Nerves, 162, 303, 321 Peripheral Nervous System, 297, 303, 320, 322 Peripheral Neuropathy, 162, 303 Peripheral Vascular Disease, 303, 304 Peristalsis, 266, 304 Peritoneal, 249, 285, 299, 304 Peritoneal Cavity, 249, 285, 299, 304 Pesticides, 122, 251, 304 Petrolatum, 269, 304 Petroleum, 301, 304 PH, 3, 15, 155, 253, 304 Pharmaceutical Solutions, 267, 304 Pharmacokinetic, 81, 304 Pharmacologic, 23, 24, 33, 246, 278, 304, 325, 326 Pharynx, 281, 296, 304, 329 Phenolphthalein, 269, 304 Phenotype, 20, 25, 35, 116, 304 Phentolamine, 150, 304 Phenyl, 112, 159, 304 Phenylalanine, 200, 304, 328 Pheromone, 59, 304 Phosphodiesterase, 52, 173, 304 Phosphodiesterase Inhibitors, 173, 304 Phospholipases, 304, 319 Phospholipids, 272, 288, 305 Phosphorous, 166, 305 Phosphorus, 254, 305 Phosphorylation, 40, 305, 311 Photoperiod, 155, 305 Physical Examination, 22, 276, 305 Physiologic, 17, 19, 27, 33, 62, 135, 136, 139, 140, 190, 191, 196, 243, 251, 258, 266, 273, 278, 281, 292, 305, 309, 313, 315, 327 Pigment, 251, 290, 291, 305 Pilot study, 9, 16, 49, 68, 103, 305 Pineal Body, 305 Pineal gland, 155, 305 Pituitary Gland, 180, 262, 277, 305 Placenta, 248, 271, 274, 305, 309, 328 Plana, 305, 318 Plants, 117, 161, 163, 189, 243, 249, 253, 255, 259, 276, 294, 298, 305, 316, 321, 326

346 Testosterone

Plaque, 98, 249, 305 Plasma cells, 246, 306 Plasma protein, 243, 306, 318 Plasma Volume, 252, 293, 306 Plasmids, 41, 306 Plasticity, 7, 62, 306 Plasticizers, 55, 306 Plastids, 300, 306 Platelet Activation, 306, 319 Platelet Aggregation, 297, 306 Platelets, 248, 297, 306, 325 Pleural, 299, 306 Pleural cavity, 299, 306 Poisoning, 248, 285, 296, 306 Polycystic, 22, 25, 46, 55, 92, 104, 225, 281, 306 Polycystic Ovary Syndrome, 92, 281, 306 Polyglutamic Acid, 152, 306 Polymerase, 306, 309 Polymers, 152, 306, 311 Polymorphism, 71, 91, 307 Polypeptide, 244, 259, 280, 307, 309, 310, 320, 331 Polysaccharide, 247, 256, 307, 328 Population Growth, 192, 307 Posterior, 245, 249, 267, 285, 301, 305, 307 Postmenopausal, 4, 10, 69, 71, 74, 78, 79, 80, 90, 103, 108, 141, 153, 164, 206, 271, 300, 307 Postnatal, 12, 34, 307, 321 Postoperative, 104, 307 Postsynaptic, 307, 319, 323 Post-translational, 15, 245, 307, 318 Potassium, 42, 106, 166, 173, 210, 293, 307 Potassium Channels, 42, 307 Potentiates, 284, 307 Potentiating, 183, 307 Potentiation, 307, 319 Practicability, 307, 327 Practice Guidelines, 223, 307 Precipitation, 152, 156, 176, 307 Preclinical, 11, 13, 33, 47, 307 Predisposition, 5, 21, 307 Prednisolone, 156, 176, 308 Preeclampsia, 12, 308 Prefrontal Cortex, 140, 308 Pregnancy Tests, 276, 308 Pregnenolone, 55, 94, 128, 147, 179, 308 Premalignant, 308, 310 Premedication, 308, 316 Premenopausal, 84, 85, 107, 135, 153, 175, 207, 308

Prenatal, 23, 47, 132, 268, 308 Preoptic Area, 47, 56, 308 Presynaptic, 308, 323 Prevalence, 14, 18, 30, 39, 164, 194, 308 Priapism, 48, 99, 308 Primary endpoint, 25, 50, 308 Primary Prevention, 210, 308 Primary tumor, 35, 308 Procaine, 288, 308 Prodrug, 96, 308 Progeny, 260, 308 Progestogen, 153, 309 Progression, 3, 5, 6, 23, 26, 28, 30, 35, 47, 50, 79, 95, 186, 191, 246, 309 Projection, 59, 298, 299, 308, 309, 314 Prolactin, 28, 60, 70, 79, 91, 98, 116, 132, 133, 266, 309 Prolactinoma, 105, 309 Promoter, 25, 36, 37, 309 Promotor, 55, 309 Prone, 44, 309 Prophase, 294, 299, 309, 323 Prophylaxis, 163, 308, 309 Proportional, 60, 309 Propranolol, 249, 309 Prospective study, 58, 289, 309 Prostaglandin, 22, 150, 309 Prostaglandins A, 309, 310 Prostate gland, 310 Prostatectomy, 50, 310, 312 Prostatic Hyperplasia, 3, 15, 125, 135, 310 Prostatic Intraepithelial Neoplasia, 46, 50, 310 Prosthesis, 194, 310 Protease, 259, 310 Protective Agents, 254, 310 Protein Binding, 310, 325 Protein C, 31, 35, 56, 166, 243, 244, 248, 250, 288, 295, 310, 327, 328 Protein Conformation, 35, 244, 310 Protein Kinases, 53, 310 Protein S, 132, 136, 200, 225, 226, 252, 280, 310, 311 Protein-Tyrosine Kinase, 275, 311 Proteinuria, 308, 311 Protocol, 11, 15, 17, 26, 62, 311 Protons, 244, 280, 285, 311, 312 Protozoa, 260, 287, 292, 311, 321, 324 Proximal, 34, 266, 296, 308, 311, 317 Pseudorabies, 5, 311 Psychiatric, 18, 21, 25, 29, 48, 58, 194, 292, 311

Index 347

Psychiatry, 17, 21, 25, 57, 71, 73, 88, 94, 98, 99, 102, 103, 107, 273, 311, 322 Psychic, 258, 288, 311, 317 Psychogenic, 151, 175, 311 Psychology, 53, 59, 82, 97, 110, 266, 311 Psychosexual, 59, 311 Psychotomimetic, 245, 265, 311 Puberty, 8, 21, 30, 40, 45, 46, 49, 51, 77, 84, 90, 147, 165, 181, 274, 311 Public Health, 9, 16, 17, 18, 33, 42, 223, 311 Public Policy, 221, 311 Publishing, 64, 164, 311 Pulmonary, 31, 252, 261, 262, 271, 278, 286, 311, 312, 330 Pulmonary Artery, 252, 312, 330 Pulmonary Edema, 286, 312 Pulmonary hypertension, 262, 312 Pulse, 25, 294, 312 Putamen, 250, 262, 296, 312 Putrescine, 300, 312, 320 Pyridoxal, 300, 312 Q Quality of Life, 44, 63, 82, 89, 136, 139, 164, 203, 312 Quaternary, 310, 312, 316 Quinones, 182, 312 R Race, 14, 20, 47, 182, 266, 287, 293, 298, 312 Radiation, 6, 66, 84, 108, 161, 168, 189, 270, 272, 273, 274, 281, 285, 312, 313, 331 Radiation therapy, 272, 285, 286, 312, 313, 331 Radical prostatectomy, 35, 91, 312 Radio Waves, 265, 293, 312 Radioactive, 278, 280, 283, 285, 286, 294, 298, 312, 313, 331 Radiography, 276, 312 Radioimmunoassay, 13, 200, 312 Radioimmunotherapy, 313 Radiolabeled, 252, 286, 312, 313, 331 Radiosensitization, 169, 313 Radiotherapy, 84, 169, 253, 286, 312, 313, 331 Random Allocation, 313 Randomization, 29, 313 Randomized, 11, 13, 17, 20, 29, 46, 49, 50, 62, 79, 99, 104, 135, 136, 138, 268, 313 Reactive Oxygen Species, 28, 313 Reagent, 274, 313 Receptors, Serotonin, 313, 318 Recombinant, 27, 55, 145, 178, 313, 330 Recombination, 26, 260, 275, 313

Rectal, 201, 250, 313 Rectum, 247, 253, 265, 273, 275, 283, 284, 286, 310, 313 Recurrence, 191, 257, 258, 303, 314 Red blood cells, 166, 270, 314, 316 Red Nucleus, 249, 314 Refer, 1, 159, 254, 259, 273, 274, 276, 279, 289, 297, 313, 314, 317 Reflex, 151, 175, 314 Refraction, 314, 320 Refractory, 92, 99, 314 Regeneration, 60, 62, 314 Regimen, 83, 105, 149, 153, 154, 268, 302, 314, 315 Regression Analysis, 60, 314 Relapse, 158, 314 Relaxin, 106, 314 Remission, 314 Renal cell cancer, 168, 314 Renin, 23, 30, 246, 314 Renin-Angiotensin System, 23, 30, 314 Reproductive system, 42, 45, 155, 185, 310, 314 Research Design, 51, 315 Resection, 154, 315, 327 Resorption, 29, 315 Respiration, 7, 247, 255, 293, 315 Restoration, 6, 122, 315, 331 Retina, 258, 287, 300, 315, 318 Retinoblastoma, 26, 225, 315 Retreatment, 91, 315 Retrograde, 5, 154, 315 Retroperitoneal, 242, 315 Retropubic, 310, 312, 315 Retropubic prostatectomy, 312, 315 Rheumatism, 282, 315 Rheumatoid, 72, 259, 315 Rheumatoid arthritis, 72, 259, 315 Rhinitis, 163, 315 Rhinorrhea, 309, 315 Rhythmicity, 57, 97, 315 Ribose, 242, 299, 315 Rigidity, 151, 175, 188, 302, 305, 315 Risk factor, 12, 17, 18, 22, 38, 39, 42, 50, 160, 270, 289, 309, 315 Rod, 250, 258, 315 Rosiglitazone, 56, 92, 316 S Saline, 149, 316 Saliva, 82, 316 Salivary, 66, 90, 93, 104, 132, 265, 272, 301, 316

348 Testosterone

Salivary glands, 265, 272, 316 Sampling Studies, 33, 316 Saponins, 316, 321 Satellite, 63, 103, 316 Schizoid, 316, 331 Schizophrenia, 162, 316, 331 Schizotypal Personality Disorder, 316, 331 Sclerosis, 25, 140, 162, 225, 259, 294, 316 Scopolamine, 193, 316 Screening, 120, 177, 258, 316 Scrotum, 163, 166, 194, 263, 316, 324, 329 Sebaceous, 316, 330 Sebaceous gland, 316, 330 Seborrhea, 182, 316 Seborrhoea, 159, 316 Sebum, 316 Secondary tumor, 292, 317 Secretory, 15, 133, 164, 222, 310, 317, 323 Sedative, 257, 293, 317 Sedentary, 11, 317 Segregation, 313, 317 Seizures, 302, 317 Selective estrogen receptor modulator, 317, 324 Selenium, 123, 317 Self Care, 241, 317 Sella, 267, 305, 317 Semen, 45, 122, 250, 268, 310, 317 Seminal vesicles, 71, 166, 200, 317, 329 Seminiferous Epithelium, 85, 317 Seminiferous tubule, 245, 284, 317, 320 Semisynthetic, 271, 317 Senile, 300, 317 Sensitization, 93, 122, 168, 317 Septal, 288, 317 Septum, 110, 317, 318 Septum Pellucidum, 317, 318 Sequence Homology, 303, 318 Serologic, 282, 318 Serotonin, 7, 26, 70, 140, 294, 313, 318, 327 Serrata, 127, 258, 318 Serrated, 318 Sertraline, 121, 318 Serum Albumin, 113, 121, 122, 124, 312, 318 Sex Characteristics, 21, 166, 180, 242, 245, 299, 311, 318, 324 Sex Determination, 225, 318 Sex Hormone-Binding Globulin, 104, 108, 177, 318 Sexually Transmitted Diseases, 192, 318 Shock, 60, 66, 162, 280, 318, 327

Side effect, 40, 42, 44, 147, 149, 154, 165, 169, 170, 188, 213, 216, 222, 242, 251, 318, 326 Signal Transduction, 8, 40, 58, 318 Signs and Symptoms, 314, 319 Skeletal, 9, 11, 17, 18, 28, 63, 133, 136, 148, 245, 258, 286, 295, 319, 320, 327 Skeleton, 17, 18, 241, 273, 286, 309, 319 Skull, 319, 324 Sleep apnea, 7, 319 Small intestine, 188, 258, 280, 285, 319 Smooth muscle, 52, 151, 173, 175, 244, 253, 254, 261, 273, 279, 287, 294, 314, 319, 320, 322 Social Behavior, 319, 331 Social Environment, 312, 319 Sodium, 148, 166, 293, 319, 322 Soft tissue, 253, 319 Solid tumor, 246, 319 Solvent, 156, 176, 251, 300, 304, 319 Soma, 319 Somatic, 5, 6, 45, 132, 242, 258, 288, 291, 293, 303, 308, 319, 324, 329 Somatic cells, 45, 291, 293, 319 Somatic mutations, 5, 319 Somatostatin, 64, 298, 320 Songbirds, 10, 62, 132, 320 Spasm, 150, 173, 247, 320 Specialist, 231, 320 Species, 36, 51, 59, 132, 157, 161, 189, 269, 270, 274, 276, 280, 287, 291, 293, 294, 304, 306, 312, 313, 318, 319, 320, 322, 324, 327, 330, 331 Specificity, 5, 24, 74, 243, 248, 320, 325 Spectrometer, 31, 320 Spectrum, 22, 27, 263, 286, 293, 312, 320 Sperm, 37, 45, 83, 95, 117, 122, 124, 192, 241, 245, 257, 317, 319, 320, 324, 329 Sperm Head, 241, 320 Spermatic, 5, 320 Spermatids, 112, 122, 124, 320 Spermatocytes, 320 Spermatogenesis, 6, 27, 38, 40, 61, 64, 70, 85, 86, 89, 96, 122, 165, 180, 190, 191, 320 Spermatogonia, 6, 320 Spermatozoa, 250, 317, 320, 329 Spermidine, 300, 320 Spinal cord, 6, 67, 162, 249, 253, 256, 257, 292, 296, 297, 301, 303, 308, 314, 320, 321, 322 Spinal Nerves, 303, 321 Sporadic, 149, 296, 315, 321

Index 349

Spores, 167, 168, 321 Standard therapy, 154, 321 Stanozolol, 129, 165, 321 Steady state, 34, 321 Steel, 258, 321 Stem Cells, 42, 60, 271, 321, 328 Sterility, 61, 74, 78, 100, 283, 321 Stimulant, 24, 245, 254, 262, 265, 279, 286, 321 Stimulus, 13, 52, 242, 267, 268, 284, 286, 314, 321, 325 Stomach, 241, 265, 271, 275, 276, 280, 296, 304, 319, 321 Stomatitis, 163, 321 Stool, 283, 286, 321 Streptozocin, 30, 321 Stria, 56, 321 Striatum, 188, 296, 321 Stroke, 142, 160, 162, 164, 220, 255, 321 Stroma, 302, 322 Stromal, 17, 269, 322 Stupor, 287, 296, 322 Subacute, 283, 322 Subclinical, 283, 317, 322 Subcutaneous, 73, 192, 242, 268, 287, 299, 302, 322 Sublingual, 73, 149, 322 Subspecies, 320, 322 Substance P, 292, 309, 317, 322 Substrate, 14, 31, 34, 55, 322, 328 Sudden death, 46, 322 Superoxide, 31, 168, 173, 322 Superoxide Dismutase, 168, 322 Suppurative, 182, 277, 322 Surgical castration, 76, 149, 322 Suspensions, 151, 322 Sweat, 279, 316, 322 Sweat Glands, 316, 322 Sympathetic Nervous System, 250, 301, 322, 323 Sympathomimetic, 245, 265, 267, 270, 286, 298, 323, 328 Symphysis, 310, 323 Symptomatic, 257, 323 Symptomatic treatment, 257, 323 Synapses, 62, 297, 299, 323 Synapsis, 323 Synaptic, 40, 297, 319, 323 Synaptic Transmission, 297, 323 Synaptic Vesicles, 323 Synergistic, 96, 132, 309, 323 Syphilis, 300, 323

Syrinx, 320, 323 Systolic, 160, 281, 323 Systolic blood pressure, 160, 323 T Tachycardia, 323, 326 Tamoxifen, 78, 317, 324 Telangiectasia, 225, 324 Telomerase, 43, 324 Temporal, 13, 15, 59, 155, 196, 324 Teratogenic, 243, 324 Terfenadine, 120, 324 Terminalis, 56, 324, 325 Territoriality, 103, 324 Testicles, 194, 245, 263, 300, 316, 322, 324, 329 Testis, 5, 6, 27, 34, 40, 121, 158, 171, 190, 194, 245, 246, 271, 288, 299, 300, 320, 324 Tetrahymena, 112, 324 Thalamic, 249, 324 Thalamic Diseases, 249, 324 Thalamus, 262, 265, 288, 308, 324 Therapeutics, 13, 14, 69, 79, 111, 215, 294, 324 Thermal, 163, 174, 253, 266, 297, 324 Thermoregulation, 155, 305, 324 Thigh, 273, 324 Third Ventricle, 282, 305, 324, 325 Thorax, 241, 325, 329 Threonine, 303, 325 Threshold, 29, 78, 118, 193, 281, 325 Thrombin, 273, 306, 310, 325 Thrombomodulin, 310, 325 Thrombosis, 311, 321, 325 Thrombus, 262, 283, 295, 306, 325 Thymus, 179, 282, 290, 325 Thyroid, 31, 123, 178, 282, 325, 328 Thyroid Gland, 325 Thyroid Hormones, 123, 325, 328 Thyrotropin, 282, 325 Thyroxine, 123, 200, 243, 304, 325 Tin, 303, 325 Tissue Distribution, 19, 325 Tolerance, 31, 33, 177, 241, 276, 325 Tomography, 253, 325 Tonic, 292, 326 Toothache, 41, 326 Topical, 29, 81, 84, 90, 102, 150, 175, 192, 193, 195, 206, 208, 280, 292, 301, 304, 326 Torsades de Pointes, 94, 326 Torsion, 194, 283, 326 Toxaemia, 308, 326

350 Testosterone

Toxic, iv, 122, 243, 249, 251, 260, 270, 282, 292, 297, 312, 317, 326 Toxicity, 56, 117, 147, 195, 267, 326 Toxicology, 105, 118, 120, 123, 222, 326 Toxins, 247, 276, 283, 294, 313, 326 Trace element, 253, 274, 325, 326 Trachea, 253, 287, 304, 325, 326 Traction, 258, 326 Transcriptase, 324, 326 Transcription Factors, 15, 37, 326 Transduction, 56, 318, 326 Transfection, 41, 252, 326 Translational, 17, 326 Translocation, 122, 326 Transmitter, 241, 249, 267, 291, 298, 323, 326, 328 Transurethral, 154, 310, 327 Transurethral Resection of Prostate, 310, 327 Trauma, 162, 194, 250, 278, 296, 324, 327 Treatment Outcome, 16, 327 Tremor, 188, 302, 327 Tricuspid Atresia, 262, 327 Trigeminal, 41, 327 Triglyceride, 178, 281, 327 Troglitazone, 56, 327 Trophic, 8, 54, 327 Tropomyosin, 295, 327 Troponin, 295, 327 Truncal, 9, 327 Tryptophan, 259, 318, 327 Tuberculosis, 261, 290, 300, 327 Tuberous Sclerosis, 225, 327 Tumor marker, 251, 327 Tumor Necrosis Factor, 79, 100, 327 Tumour, 159, 328 Type 2 diabetes, 46, 101, 185, 328 Tyramine, 294, 328 Tyrosine, 267, 311, 328 U Ubiquitin, 29, 328 Ultrasonography, 276, 328 Umbilical Arteries, 328 Umbilical Cord, 60, 328 Umbilical cord blood, 60, 328 Unconscious, 282, 328 Urbanization, 91, 328 Urea, 31, 286, 300, 322, 328 Uremia, 286, 328 Ureters, 328, 329 Urethra, 251, 281, 302, 310, 327, 328, 329 Uridine Diphosphate, 276, 328

Uridine Diphosphate Glucuronic Acid, 276, 328 Urinary, 92, 116, 166, 172, 173, 182, 254, 258, 263, 275, 283, 299, 310, 315, 316, 328, 329 Urinary tract, 172, 173, 329 Urinate, 329, 331 Urine, 50, 73, 75, 154, 247, 251, 252, 266, 271, 276, 279, 283, 286, 299, 311, 314, 328, 329 Urogenital, 153, 172, 173, 275, 329 Urticaria, 324, 329 Uterine Contraction, 301, 329 Uterus, 43, 257, 262, 269, 272, 273, 282, 287, 292, 300, 309, 314, 329 V Vaccine, 33, 242, 311, 329 Vacuoles, 300, 329 Vagina, 173, 257, 292, 314, 329 Vaginal, 150, 183, 289, 329 Vagus Nerve, 327, 329 Valves, 250, 329 Varices, 250, 329 Vas Deferens, 320, 329 Vascular endothelial growth factor, 10, 329 Vascular Headaches, 251, 329 Vasectomy, 192, 329 Vasoconstriction, 13, 270, 329 Vasodilatation, 151, 175, 329 Vasodilator, 112, 150, 251, 253, 267, 279, 329 Vasomotor, 271, 329 VE, 110, 138, 329 Vector, 326, 330 Vein, 285, 298, 316, 328, 330 Venous, 39, 151, 175, 253, 299, 311, 327, 330 Venous blood, 39, 253, 330 Ventral, 72, 83, 131, 282, 321, 330 Ventricle, 249, 256, 262, 312, 323, 325, 327, 330 Ventricular, 10, 261, 326, 327, 330 Ventricular fibrillation, 326, 330 Vertebrae, 321, 330 Vertebral, 18, 305, 330 Vesicular, 113, 124, 278, 279, 293, 330 Veterinarians, 157, 330 Veterinary Medicine, 221, 330 Viral, 5, 126, 254, 326, 330 Virilism, 281, 330 Virilization, 165, 330

Index 351

Virulence, 249, 326, 330 Virus, 5, 58, 65, 88, 92, 250, 254, 269, 277, 284, 305, 326, 330 Viscera, 319, 330 Visceral, 36, 101, 160, 250, 287, 288, 329, 330 Viscosity, 78, 330 Vitro, 5, 6, 7, 24, 30, 32, 34, 35, 37, 41, 55, 61, 62, 63, 65, 68, 72, 74, 85, 92, 93, 97, 121, 122, 132, 145, 149, 182, 222, 283, 330 Vivo, 26, 36, 55, 59, 63, 111, 153, 190, 330 Vocal cord, 166, 331 Void, 45, 331 Volition, 285, 331 Vomeronasal Organ, 59, 299, 331 W Wart, 32, 331 Weight Gain, 9, 12, 63, 79, 87, 139, 331

White blood cell, 246, 250, 283, 287, 290, 306, 331 Windpipe, 304, 325, 331 Withdrawal, 85, 157, 301, 304, 331 Womb, 314, 329, 331 Wound Healing, 291, 331 X Xenograft, 116, 246, 331 X-ray, 35, 246, 253, 274, 285, 290, 298, 312, 313, 331 X-ray therapy, 286, 331 Y Yeasts, 274, 304, 331 Yohimbine, 154, 331 Z Zygote, 260, 331 Zymogen, 310, 331

352 Testosterone

Testosterone - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Low Testosterone: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Influenza A - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lipomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Barbiturates - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cephalexin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lymphedema - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Vaginitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Feet - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Benzene - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Erythema Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Alopecia Areata - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Endometritis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Testosterone - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Low Testosterone: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Influenza A - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lipomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Barbiturates - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cephalexin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lymphedema - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Vaginitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Feet - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Benzene - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Erythema Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Alopecia Areata - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Endometritis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Recommend Documents