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

AMENORRHEA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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

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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., 1960Amenorrhea: 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: 0-597-84328-7 1. Amenorrhea-Popular works. I. Title.

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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.

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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 amenorrhea. 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.

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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.

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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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON AMENORRHEA .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Amenorrhea................................................................................... 8 The National Library of Medicine: PubMed ................................................................................ 31 CHAPTER 2. NUTRITION AND AMENORRHEA ................................................................................ 57 Overview...................................................................................................................................... 57 Finding Nutrition Studies on Amenorrhea ................................................................................. 57 Federal Resources on Nutrition ................................................................................................... 61 Additional Web Resources ........................................................................................................... 61 CHAPTER 3. ALTERNATIVE MEDICINE AND AMENORRHEA .......................................................... 63 Overview...................................................................................................................................... 63 National Center for Complementary and Alternative Medicine.................................................. 63 Additional Web Resources ........................................................................................................... 68 General References ....................................................................................................................... 74 CHAPTER 4. DISSERTATIONS ON AMENORRHEA ............................................................................ 75 Overview...................................................................................................................................... 75 Dissertations on Amenorrhea ...................................................................................................... 75 Keeping Current .......................................................................................................................... 76 CHAPTER 5. CLINICAL TRIALS AND AMENORRHEA....................................................................... 77 Overview...................................................................................................................................... 77 Recent Trials on Amenorrhea ...................................................................................................... 77 Keeping Current on Clinical Trials ............................................................................................. 78 CHAPTER 6. PATENTS ON AMENORRHEA ....................................................................................... 81 Overview...................................................................................................................................... 81 Patents on Amenorrhea................................................................................................................ 81 Patent Applications on Amenorrhea............................................................................................ 89 Keeping Current .......................................................................................................................... 95 CHAPTER 7. BOOKS ON AMENORRHEA .......................................................................................... 97 Overview...................................................................................................................................... 97 Book Summaries: Federal Agencies.............................................................................................. 97 Book Summaries: Online Booksellers........................................................................................... 98 Chapters on Amenorrhea ............................................................................................................. 98 CHAPTER 8. PERIODICALS AND NEWS ON AMENORRHEA........................................................... 101 Overview.................................................................................................................................... 101 News Services and Press Releases.............................................................................................. 101 Newsletter Articles .................................................................................................................... 103 Academic Periodicals covering Amenorrhea.............................................................................. 105 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 107 Overview.................................................................................................................................... 107 U.S. Pharmacopeia..................................................................................................................... 107 Commercial Databases ............................................................................................................... 108 Researching Orphan Drugs ....................................................................................................... 109 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 113 Overview.................................................................................................................................... 113 NIH Guidelines.......................................................................................................................... 113 NIH Databases........................................................................................................................... 115 Other Commercial Databases..................................................................................................... 117 The Genome Project and Amenorrhea ....................................................................................... 117 APPENDIX B. PATIENT RESOURCES ............................................................................................... 121

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Overview.................................................................................................................................... 121 Patient Guideline Sources.......................................................................................................... 121 Finding Associations.................................................................................................................. 126 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 129 Overview.................................................................................................................................... 129 Preparation................................................................................................................................. 129 Finding a Local Medical Library................................................................................................ 129 Medical Libraries in the U.S. and Canada ................................................................................. 129 ONLINE GLOSSARIES................................................................................................................ 135 Online Dictionary Directories ................................................................................................... 137 AMENORRHEA DICTIONARY................................................................................................. 139 INDEX .............................................................................................................................................. 193

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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 amenorrhea 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 amenorrhea, 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 amenorrhea, 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 amenorrhea. 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 amenorrhea, 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 amenorrhea. The Editors

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

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and amenorrhea, 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 “amenorrhea” (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 Female Athlete Triad Source: Orthopedics and Sports Medicine. 3(1). 1999. Summary: Furia describes the syndrome known as Female Athlete Triad. This consists of disordered eating leading to amenorrhea, or cessation of menstrual periods, and osteoporosis. The author discusses how female athletes develop disordered eating as a result of unrealistic expectations from coaches, families, and themselves. The triad is most commonly found among athletes participating in sports in which appearance is important, such as gymnastics and figure skating; sports with weight classes, for example horse racing and martial arts; and endurance sports, like marathon running and swimming. Furia describes in detail each of the conditions that make up the triad, and distinguishes disordered eating from eating disorders by the presence of psychiatric symptoms in the latter. Diagnosis may be difficult, says Furia, because athletes suffering

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from the triad conceal their behavior. Treatment consists of reestablishing healthy eating behaviors and therapy as needed to treat depression and poor self-esteem. Furia calls for education of coaches and parents as to the dangers of the triad. He points especially to amenorrhea as a danger sign, which many coaches ignore, accepting it a mere side effect of hard training. (27 refs.). •

Carotid Artery Atheromas in Post-Menopausal Women: Their Prevalence on Panoramic Radiographs and Their Relationship to Atherogenic Risk Factors Source: JADA. Journal of the American Dental Association. 132(8): 1130-1136. August 2001. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: More than 60 percent of the deaths in the United States attributed to stroke occur in postmenopausal women. As estrogen levels decline, atherosclerotic lesions (atheromas) develop in the region of the carotid bifurcation (where the carotid artery splits in the neck) and have been implicated as the precipitating cause in the majority of these strokes. Atheromas often are calcified and have been detected on the panoramic radiographs of neurologically asymptomatic male veterans; however, similar studies have not been conducted among female veterans. This article reports on a study in which the authors assessed panoramic radiographs and medical records of 52 neurologically asymptomatic female veterans (mean age, 70.4 years), with a history of amenorrhea (cessation of menstruation) of more than 12 months' duration, for atheromas and risk factors associated with atherosclerosis. The radiographs (x rays) of 16 subjects (31 percent) exhibited atheromas located in the neck about 2.0 centimenters inferior and posterior to the angle of the mandible (lower jaw). These findings were confirmed in all instances by the presence of atheromas on anteroposteriod cervical sping radiographs. The medical histories of these subjects were heavily laden with atherogenic risk factors (hypertension, 94 percent; overweight, 25 percent; obesity, 25 percent; smoking more than 15 pack years, 38 percent; hyperlipidemia, 69 percent; type 2 diabetes mellitus, 21 percent). Hypertension (high blood pressure) was significantly associated with the presence of atheromas. The authors conclude that some neurologically asymptomatic women at high risk of developing stroke can be identified in the dental office via panoramic radiography. Dentists should refer patients with such calcifications to an appropriate physician for further evaluation and treatment. 2 figures. 1 table. 33 references.

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The Fit Woman of the 21st Century: Making Lifelong Exercise the Norm Source: The Physician and Sportsmedicine. 26(8):23-24,30. August 1998. Contact: The Physician and Sportsmedicine, 4530 W. 77th St., Minneapolis, MN 55435. (612) 835- 3222. FAX (612) 835-3460. Summary: Smith discusses the history of women's physical activity. She says that at one time, women were very active throughout life, but the recent advent of laborsaving devices in the home means a more sedentary lifestyle for most women. According to Smith, modern women must plan and actively set aside time for exercise. She notes some of the barriers for young women to active participation in sports, including parental fear of the female athlete triad (osteoporosis, disordered eating, and amenorrhea), cultural restraints, and distrust of the lifestyle of the elite athlete. Smith states that the goals for women should be to maintain activity throughout life, to ensure

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activities for girls and young women, to assure older women of appropriate physical activities, and to increase the availability of programs for all ages. •

Passions, Risks, and Benefits Source: Healthy Weight Journal. p.49,64. July/August 2000. Contact: B.C. Decker, Inc. 4 Hughson St. South, O.O. Box 620, LCD1, Hamilton, Ontario L8N 3K7, Canada. 800-568-7281. 905-522-7017. [email protected]. Summary: The author of this editorial asserts that so many female athletes have amenorrhea that the condition is considered normal. Other elements of the female athlete triad--the dark thread running through women's sports--are eating disorders and osteoporosis. Female athletes, like other athletes, often are willing to take risks for their sport, but performance and health go together. Thus athletes and coaches need to be alert to problems that can lead to deterioration in physical and psychological health. Sport organizations have taken some steps to prevent eating disorders from developing in athletes, and education has increased awareness of eating disorders, especially among coaches. Early detection is still the best hope of recovery. Young women should be encouraged to participate in sports; parents and coaches should remain vigilant against the risks that do exist.

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Efficacy of Mycophenolate Mofetil in Patients with Diffuse Proliferative Lupus Nephritis Source: New England Journal of Medicine. 343(16): 1156-1162. October 19, 2000. Summary: The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis (kidney inflammation associated with systemic lupus erythematosus or SLE) but has serious adverse effects. This article reports on a study that investigated the efficacy of mycophenolate mofetil in patients (n = 42) with proliferative lupus nephritis. The authors compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months (group 1) with those of a regimen of prednisolone and cyclophosphamide given for 6 months, followed by prednisolone and azathioprine for 6 months (group 2). Of the patients in Group 1 (n = 21), 81 percent had a complete remission, and 14 percent had a partial remission, as compared with 76 percent and 14 percent, respectively, of the 21 patients in Group 2. The improvements in the degree of proteinuria (protein in the urine) and the serum albumin (protein levels in the blood) and creatinine concentrations were similar in the two groups. One patient in each group discontinued treatment because of side effects. Infections were noted in 19 percent of the patients in Group 1 and in 33 percent of those in Group 2. Other adverse effects occurred only in group 2; they included amenorrhea (23 percent), hair loss (19 percent), leukopenia (10 percent), and death (10 percent). The rates of relapse were 15 percent in Group 1, and 11 percent in Group 2. The authors conclude that for the treatment of diffuse proliferative lupus nephritis, the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone, with similar levels of toxicity. 2 figures. 4 tables. 15 references.

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Female Athlete Triad: Challenges in Nutrition Practice Source: Healthy Weight Journal. p.52-54. July/August 2000. Contact: B.C. Decker, Inc. 4 Hughson St. South, O.O. Box 620, LCD1, Hamilton, Ontario L8N 3K7, Canada. 800-568-7281. 905-522-7017. [email protected].

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Summary: This article describes the symptoms and treatment options for disordered eating, amenorrhea, and osteoporosis--the female athlete triad. The disordered eating pattern, along with undernourishment and a high activity level, lead to amenorrhea. The accompanying decrease in estrogen levels causes more rapid absorption of bone tissue by the body and a decrease in bone density, setting the stage for the development of osteoporosis. Each of the symptoms of the triad are described, as are the prevalence of each symptom and the screening tools used to identify the signs of the triad. The author recommends that treatment of each element of the female athlete triad be integrated into the nutrition therapy program. She concludes that awareness and education efforts need to send the dual message that the triad has negative consequences for the female athlete and that it can be successfully treated without compromising the athlete's performance. •

Complications of Eating Disorders Source: Healthy Weight Journal. 115(2):28-29. March/April 2001. Summary: This article summarizes the mental and physical complications commonly associated with anorexia nervosa and bulimia. Many of the symptoms of anorexia nervosa are directly related to the physical effects of starvation while others deal with attitudes and behavior toward eating and weight. Mental complications for anorexia nervosa include decreased energy, moodiness, denial of the eating disorder, inability to concentrate, social withdrawal, preoccupations with body, misperception of hunger and other bodily sensations, and sleep disturbance. Physical complications include electrolyte imbalance, gastrointestinal and cardiovascular disturbances, abnormal temperature regulation, decreased bone mineral density, amenorrhea, anemia, and neurological, renal, and musculocutaneous changes. The person with bulimia may be of normal weight and may not experience the effects of starvation. The mental symptoms associated with bulimia include anxiety, depression, and other negative emotions; poor impulse control; feelings of isolation; constant concern with weight and body image; preoccupation with eating and food; purging and a binge/purge cycle; and dishonesty, lying, stealing, and suicidal tendencies or attempts. Physical problems associated with bulimia include electrolyte imbalance, gastrointestinal and cardiovascular disturbances, possible aspiration pneumonia due to aspiration of vomitus, possible abnormal temperature regulation, menstrual irregularities, possible anemia, neurological and musculocutaneous changes, and dental enamel erosion with vomiting.

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Osteoporosis in Young, Athletic Women Source: Journal of Musculoskeletal Medicine. 13(6):15-22; June 1996. Summary: This journal article discusses factors associated with bone loss in women athletes, offers advice for early detection of osteoporosis, and provides guidelines on preventing osteoporosis and suggestions for managing it when it does occur. The authors reveal that exercise, calcium intake, and estrogen levels all affect the status of bone in young women athletes. In premenopausal women, menstrual dysfunction, especially amenorrhea, suggests a lack of estrogen and is a special cause for concern because of its association with low bone mineral density (BMD) and increased incidence of stress fracture. The condition is more common in athletes; lean body weight, caloric restriction, and a strenuous training regimen may be contributing factors. Diagnosis is based on the office evaluation, which may be supplemented with BMD measurement (dual-energy x-ray absorptionmetry is the most accurate method). Successful management depends on a program of education, diet, and exercise modification. Some patients may also benefit from estrogen replacement therapy. 4 figures, 31 references. (AA-M).

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Stress Injury to Bone in the Female Athlete Source: Clinics in Sports Medicine. 16(2):197-224; April 1997. Summary: This journal article for health professionals explores stress injury to bone in the female athlete. Stress injury is defined, and an overview of bone biology is presented. Risk factors for stress injury are identified, including low-peak bone mass, female gender, Caucasian ethnicity, and age. Other risk factors include extrinsic mechanical factors such as training regimen, footwear, fitness level, and running surface; intrinsic mechanical factors such as tibial bone width and area moments of inertia and external rotation of the hip; hormonal factors such as exercise-associated delayed menarche, hypothalamic hypoestrogenic amenorrhea, ovulatory disturbances, oral contraceptive pill use, and testosterone level; and nutritional factors such as inadequate dietary calcium and vitamin D intake, disordered eating and inadequate calories, and anorexia nervosa. The article also discusses osteoporosis in the female athlete, the use of bone density assessment, and the prevention and treatment of stress injury to bone. Prevention of bone injury includes maximizing peak bone mass and adhering to sound principles of training. Treatment may include correcting mechanical factors; undergoing hormone replacement therapy; and maintaining adequate calcium, vitamin D, and caloric intake. 131 references, 3 figures, and 1 table.

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Active Woman: Special Health Concerns Source: Patient Care. 32(12): 184-186,189,193-195. July 15, 1998. Summary: This journal article provides health professionals with information on the special health concerns of physically active women. Women who engage in sports or exercise may develop lower extremity musculoskeletal injuries at higher rates than men, mainly because of women's generally lower levels of conditioning. Active women experience musculoskeletal problems of that differ in important ways from those of men, among them anterior cruciate ligament (ACL) injuries, patellofemoral disorders, and foot problems. Possible intrinsic factors that may explain why women have higher ACL injury rates include the effects of estrogen on the cellular matrix of the ACL, the effect of the menstrual cycle, and the width of the femoral intercondylar notch. Extrinsic factors that may cause ACL injuries at higher rates in women are lower skill and experience levels. Rest, ice, compression, and elevation should be used as soon as possible after the ACL injury. Patellofemoral disorders are associated with patellar instability and patellofemoral pain syndrome. Treatment for patellofemoral pain syndrome usually consists of a rehabilitation program focusing on quadriceps strengthening. For patellar instability, treatment includes passive restraint, quadriceps training, and behavior modification. Women also have more foot problems than men. Shoes that fit improperly and (sometimes) genetic factors cause foot problems. The main treatment options are new shoes, orthotics, and bunionectomy. Women should also be evaluated for the female athlete triad of amenorrhea, osteoporosis, and disordered eating. The article provides guidelines on diagnosing and managing these special concerns. 10 figures and 1 reference.

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Sports Pharmacology Source: Clinics in Sports Medicine. 17(2): i-xii, 211-396. April 1998. Summary: This journal provides health professionals with information on sports pharmacology. The first article discusses the distribution of prescription and nonprescription drugs in the training room. This is followed by an article that describes some of the medications commonly used to care for athletes, including analgesics,

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nonsteroidal anti-inflammatory drugs, muscle relaxants, antibiotics, hypnotics, antiemetics and antidiarrheals, antihistamines and decongestants, caffeine, cardiovascular drugs, oral birth control pills, and behavioral modification medications. An article on recreational drug use reviews the use of marijuana, cocaine, and alcohol among athletes and explores differences in usage among athletic and nonathletic groups and subgroups. This is followed by an article on the anabolic agents athletes use. Dehydroepiandrosterone, anabolic-androgenic steroids, human growth hormone, and insulinlike growth factor are discussed in terms of their basic chemistry and physiology, function, clinical uses, athletic uses, and side effects. The next article reviews some of the most popular ergogenic agents, focusing on creatine, beta-hydroxy-beta-methylbutyrate, chromium, erythropoietin, L-carnitine, dehydroepiandrosterone, antioxidants, boron, choline, inosine, and magnesium. The issue of athletic drug testing is the focus of the next article, which is followed by an article that discusses drug programs for those involved in sports and focuses on the components of such a program. Subsequent articles provide guidelines on the nonpharmacologic and pharmacologic management of athletic amenorrhea and the pharmacologic treatment of exercise-induced asthma. An article on the equipment and medications a team physician should take when traveling with a sports team follows. The final article discusses using nonsteroidal antiinflammatory drugs and corticosteroids as modulators of pain and inflammation resulting from sports injuries. 9 figures, 27 tables, and numerous references. •

Is Bone Deterioration in Eating Disorders Permanent? Source: Healthy Weight Journal. p.50. July/August 2000. Contact: B.C. Decker, Inc. 4 Hughson St. South, O.O. Box 620, LCD1, Hamilton, Ontario L8N 3K7, Canada. 800-568-7281. 905-522-7017. [email protected]. Summary: Weight gain, after eating disorder treatment, did not restore bone mineral density. A British study found that high levels of reduced bone density were measured in 56 eating-disordered women. Duration of amenorrhea, body mass index, frequency of vomiting, and cigarette and alcohol consumption accounted for 40 percent of the variance in spinal bone density measures. A follow-up bone scan 9 to 51 months later showed no improvement in bone density despite weight increases. The researchers reported that their study may be too short or subjects too few to record changes, but they cautioned that bone density can not be assumed to recover with weight gain.

Federally Funded Research on Amenorrhea The U.S. Government supports a variety of research studies relating to amenorrhea. 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 amenorrhea. 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).

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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 amenorrhea. The following is typical of the type of information found when searching the CRISP database for amenorrhea: •

Project Title: ADRENAL AXIS AND THE REPRODUCTIVE PROCESS Principal Investigator & Institution: Ferin, Michel J.; Professor; Obstetrics and Gynecology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 30-JUN-2005 Summary: Our overall objective is to investigate how stress, and by definition an activated hypothalamic-pituitary-adrenal axis (HPA), acts to modify normal function of the hypothalamic- pituitary-gonadal axis (HPG) and to interfere with the normal menstrual cycle in a relevant non-human primate. In the previous funding period, we developed two distinct short-term stress models (inflammatory and psychogenic) in the rhesus monkey and demonstrated that they reliably interfere with normal cyclic function and induce cycle stage- and stress-specific damage that may include a delay in folliculogenesis, a decrease in luteal secretory capability reminiscent of the inadequate luteal phase syndrome, and/or interference with the normal tonic gonadotropin profile. The first two aims will investigate the role of the 2 main HPA neuropeptides, CRH and vasopressin (VP), in the process by which stress interferes with the menstrual cycle by correlating their central release and the effects of specific CRH and VP antagonists to neutralize endogenous HPA activity. Since different stress may activate varying central pathways, which may, in turn, have different sensitivities to ovarian steroids, we will compare HPA and HPG effects in the 2 different stress models and in the follicular and luteal phase of the cycle. The goal of aim 3 is to develop a long-term stress that results in amenorrhea, the defining symptom of the established clinical functional hypothalamic chronic anovulation syndrome. Here, we will test whether two unrelated stimuli, such as a psychogenic stress and diet, can synergize to produce the syndrome and investigate the role of CRH, VP and opioid peptides in established amenorrhea. We will also investigate whether leptin, in a new role as a modulator of stress-related endocrine function and reproduction, plays a protective role against amenorrhea. Overall, the data will contribute to our understanding of the varying mechanisms whereby different stress stimuli interfere with reproductive function and of how the ovarian endocrine milieu influences this process. They will provide novel information on the early stages whereby a stress, insufficient to interrupt the cycle, interferes with normal cyclic function and may result in infertility, and open new avenues of treatment in the chronic anovulation syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANDROGEN EFFECTS AND INSULIN RESISTANCE IN HIV DISEASE Principal Investigator & Institution: Grinspoon, Steven K.; Associate Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): The goal of this application is to support my professional development as a clinical investigator and successful mentor to junior faculty and fellows in patient-oriented research My research focus has been to investigate the effects of nutritional status on neuroendocrine function, and as such, I have used HIV disease as a relevant disease model, with two funded NIH R01 grants for

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which I am the PI. The three Specific Aims of this grant stem from a significant body of work accomplished over the past few years demonstrating hypogonadism in HIVinfected women and a severe insulin resistance pattern in HIV-infected patients with lipodystrophy In these funded studies, I will investigate the mechanisms of androgen deficiency and also the effects of long-term physiologic testosterone replacement in this population Furthermore, I will study the mechanisms of insulin resistance, investigating the critical role of increased lipolysis and the effects of thiazolidinediones in this population The grant for the first Specific Aim, to study the effects of androgens in HIVinfected women, will expire at the end of this year, and a follow-up proposal, recently submitted will further investigate adrenal androgen shunting and DHEA in this population Preliminary data in this regard show a novel effect of HIV on adrenal metabolism, with shunting toward cortisol and away from androgen production The grant for the third Specific Aim is funded until 2005 I have had good success as a mentor, with two recent K-23 awardees and six former or current trainees There has been significant interest in my research from Endocrine Fellows and also from Fellows in Harvard Nutrition Division The Institutional Environment at the MGH, with a strong and diverse Endocrine Division, GCRC, and Center for AIDS Research is outstanding The Department of Medicine has made a substantial commitment toward my development as a clinical researcher responsible for training a large number of fellows However, it is clearly necessary to reduce my clinical activities in order to devote sufficient time to the training and mentoring of junior faculty and fellows The Midcareer Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support to reduce clinical and administrative responsibilities, and ensure my continued success as a mentor and clinical researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASSESSING SAFETY/EFFICACY OF TROGLITAZONE IN PCOS-POLYCYSTIC OVARY SYNDROME Principal Investigator & Institution: Legro, Richard; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2002 Summary: This is a 44 week, randomized, double-blind, placebo-controlled, multicenter study assessing the safety and efficacy of troglitazone in polycystic ovary syndrome(PCOS). The objective is to study the safety and efficacy of troglitazone in improving the manifestations of PCOS including oligo/anovulation, oligo/amenorrhea, hyperandrogenism and hirsutism. Premenopausal women with PCOS between the ages of 18-40 will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOENERGETICS DISTURBANCES

OF

EXERCISE-INDUCED

MENSTRUAL

Principal Investigator & Institution: Williams, Nancy I.; Noll Physiological Res Ctr; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 10-MAY-2001; Project End 30-APR-2004 Summary: (Scanned from the applicant's abstract) The suppression of menstrual cyclicity due to strenuous exercise can cause infertility, severe bone demineralization, increase fracture risk, and possibly increase the risk of cardiovascular disease. Recent findings in humans and animals have strongly suggested that exercise-induced menstrual disturbances are primarily caused by low energy availability and not by other

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factors, such as the physical stress of exercise per se. While some studies have quantified energy balance associated with short-term decreases in plasma levels of reproductive hormones, the bioenergetics associated with the induction and reversal of clinically recognized menstrual disturbances in exercising women remain unclear. The first specific aim of this proposal is to test the hypothesis that there is a direct relationship between the severity of exercise-induced menstrual disturbances and the magnitude of negative energy balance. In addition to weight loss, crosssectional studies in humans suggest that exercise-induced menstrual disturbances are associated with adaptive mechanisms to conserve energy, i.e., alterations in circulating metabolic hormones and substrates, and reductions in components of 24 h energy expenditure such as metabolic rate. Since in vivo and in vitro studies using animal models have suggested mechanistic roles for key metabolic hormones and substrates in the modulation of GnRH neuronal activity with changes in energy balance, prospective studies in humans are now necessary to identify the time course and magnitudes of change of potential key metabolic signals during the development of EIMD. The second specific aim of this proposal is to test the hypothesis that exercise-induced menstrual disturbances are triggered by the development of a particular metabolic state defined by adaptive mechanisms to conserve energy. The significance of this research relates to conditions of infertility, delayed puberty, anovulation, anorexia nervosa, exercise-induced amenorrhea, and the recently identified high incidence of luteal phase disturbances and anovulatory cycles in women exercising even at recreational levels. We expect the results of these studies to provide new and useful information for making specific recommendations regarding the exercise and dietary practices concomitant with maintaining normal, ovulatory menstrual cycles and adequate levels of circulating estrogen and progesterone. The results will also expand our understanding of the mechanism of the modulation of reproductive function by energy availability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN GENES GOVERNING REPRODUCTION Principal Investigator & Institution: Steiner, Robert A.; Professor; Obstetrics and Gynecology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-APR-1993; Project End 30-JUN-2003 Summary: In mammals, reproductive activity is initiated and maintained by physiological factors associated with nutrition, adiposity, and metabolism; however, little is understood about mechanisms that mediate the integration of metabolism and reproduction. Leptin is a newly discovered satiety hormone and metabolic activator, which has recently been shown to have stimulatory effects on the reproductive system and has been postulated to serve as an important conduit linking the body~s metabolic and reproductive control systems. The overall goal of this research is to understand the cellular and molecular mechanisms of leptin~s action on the neuroendocrine reproductive axis-focusing on 4 hypothalamic regions-the arcuate, dorsomedial, paraventricular, and medial preoptic nuclei. The specific aims are first, to elucidate the role of proopiomelanocortin neurons and the melanocortin type 4 receptor in mediating leptin's effect on reproductive function and to identify their anatomical substrate; second, to examine the functional significance of agouti- related protein (ARP) in mediating leptin~s action in the brain and to trace the cellular pathway of ARP~s action in the hypothalamus. These studies will be performed with laboratory rats and different lines of transgenic mice as the experimental animals. The methods used to accomplish these objectives will include various in vivo pharmacological and endocrine manipulations, hormone assays, single- an double-label in situ hybridization, antisense

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oligonucleotide blockade of neuropeptide synthesis, neuronal tract tracing, and the creation and analysis of several new lines of mutant/transgenic mice bearing alterations in one or more genes related to leptin's signaling mechanism. Learning more about the mechanisms of leptin's action on the brain may help us to understand the molecular basis of certain disorders of human reproduction (e.g., hypothalamic amenorrhea and infertility linked to metabolic wasting diseases such as diabetes mellitus) and may even provide a rationale for the development of better methods of contraception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CDB-2914 /PROGESTERONE RECEPTOR MODULATOR /VAGINAL RING Principal Investigator & Institution: Tsong, Yun-Yen; Population Council 1 Dag Hammarskjold Plaza New York, Ny 10017 Timing: Fiscal Year 2002; Project Start 30-AUG-2002; Project End 28-FEB-2007 Summary: (provided by applicant): A new progesterone receptor modulator, CDB-29 14, with potent antiovulatory properties will be investigated for its potential as a contraceptive for women when delivered through a sustained-released system such as a contraceptive vaginal ring. The molecule has been synthesized and developed by the National Institute of Child Health and Human Development (NICHD) for emergency contraception. Toxicology studies conducted at the NICHD indicate that the compound is safe, and the Food and Drug Administration (FDA) has approved an Investigational New Drug for clinical study. CDB-2914 binds to the progesterone receptor (PR) with high affinity and is a potent progesterone antgonist (PA). It exhibits potent antiovulatory properties in animal models. These properties of CDB-2914 make it attractive as a potential contraceptive, and preliminary studies suggest the possibility of delivering CDB-2914 continuously at low doses via a silastic vaginal ring. The research project described in this proposal will include the following studies: 1) The mechanism of action at the ovarian level will be explored. 2) CDB-2914 will be formulated into vaginal gel and rings and will involve assessment of in vitro release and stability studies. The extensive experience of The Population Council in laboratory scale manufacture of contraceptive rings (CRs) and in evaluation of their clinical performance provides a firm base for completing the development of the CDB-2914 device. 3) A radioimmunoassay will be set up for CDB-2914 and validated for kinetic studies to be conducted in animals and in women. 4) The potential proliferative action of CDB-2914 on human breast cells will be investigated as well for safety purposes, in anticipation of eventual long-term contraceptive efficacy studies in women. Parallel studies in women and monkeys, which relate to the above studies but for which funding has been obtained or will be requested from other sources, will be described separately. Ultimately, this new estrogen-free method should be associated with fewer side effects than estrogen-containing contraceptives and will likely induce endometrial changes resulting in amenorrhea, a condition highly acceptable to women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LACTATION

CONTROL

OF

GONADOTROPIN

SECRETION

DURING

Principal Investigator & Institution: Smith, M Susan.; Associate Professor of Physiology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002

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Summary: The reproductive state of lactation, which occurs in all mammals, is associated with an inhibition of reproductive cyclicity and ovulation due to a suppression of gonadotropin releasing hormone (GnRH), the hypothalamic neuroendocrine neurons regulating reproduction. The focus of our studies is to identify the afferent neuronal pathways activated during lactation by the suckling stimulus that are responsible for the suppression of GnRH neuronal function. This past year, we made the following observations 1) Using neuronal tract tracing techniques and confocal microscopy, we have shown that NPY neurons activated by the suckling stimulus project to areas containing GnRH neurons and make contact with GnRH neuronal processes. These results suggest a possible neuronal mechanism by which suckling inhibits GnRH neuronal activity. 2) The large increase in food intake during lactation most likely occurs in response to substances that signal changes in metabolic activit y, such as leptin (a satiety-inducing substance) and agouti-related transcript (ART, induces obesity). During lactation, blood leptin levels are greatly suppressed, whereas ART expression is increased in the hypothalamus. Current studies in the laboratory are examining the relationship between the changes in leptin and ART and the increase in NPY neuronal activity and food intake. In addition, we are exploring possible interactions between the regulation of food intake and of gonadotropin releasing hormone neuronal activity during lactation. It is well established that many causes of infertility are related to changes in energy homeostasis, such as in exercised-induced amenorrhea and anorexia nervosa. An understanding of the mechanisms by which the suckling stimulus imposes an inhibition on GnRH neuronal function provides information that is relevant to primates (including humans), in which the reproductive neuroendocrine axis regulating ovarian cyclicity is also inhibited. These studies have relevance to women's reproductive health as they will increase our understanding of hypothalamic causes of infertility and provide new approaches for contraception. FUNDING NIH HD14643 PUBLICATIONS Li C, Chen P, Smith MS. The acute suckling stimulus induces expression of Neuropeptide Y (NPY) in cells in the dorsomedial hypothalamus and increases NPY expression in the arcuate nucleus. Endocrinology 139:1645-1652, 1998. Li C, Chen P, Smith MS. Neuropeptide Y (NPY) neurons in the arcuate nucleus (ARH) and dorsomedial nucleus (DMH), areas activated during lactation, project to the paraventricular nucleus of the hypothalamus (PVH). Reg Peptides 75-76:93-100, 1998. Li C, Chen P, Smith MS. Neuropeptide Y (NPY) and tuberinfundibular dopamine (TIDA) are altered during lactation role of prolactin. Endocrinology 140 118-123,1999. Grove KL, Smith MS. Resistance of the hippocampus in the lactating rat to N-methyl-D-aspartate (NMDA)-mediated excitation is not due to a nonfunctional receptor system. Brain Res 814:157-163, 1998. Grove KL, Smith MS. 3?hydroxysteroid dehydrogenase (3? -HSD) and mRNA distribution in the rat brain. In The Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 493 (abstract #P3-527). Brogan RS, Kuper J, Duncan JS, Trayhurn P, Smith MS. Serum leptin levels during lactation are related to the metabolic drain of milk projection lack of correlation to serum LH. In The Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 349 (abstract #P2-478). Chen P, Haskell-Luevano C, Cone RD, Smith MS. Coexpression of agouti-related transcript (ART) and neuropeptide Y (NPY) in the hypothalamic arcuate nucleus of female rats during the estrous cycle and lactation. In the Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 521 (abstract #P3-663). Li C, Chen P, Smith MS. Anatomical interactions between neuropeptide Y neurons from arcuate nucleus of the hypothalamus (ARH-NPY) and the gonadotropin-releasing hormone (GnRH) in the hypothalamus. In The Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 2427, 1998), p 59 (abstract #OR5-5). Li C, Chen P, Smith MS. Neuropeptide Y neurons from

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the arcuate nucleus of the hypothalamus (ARH-NPY) directly project to corticotropin releasing hormone (CRF) neurons in the paraventricular nucleus (PVH). Soc Neurosci Abstr 24(pt 1):369, 1998 (abstract #146.8). Brogan RS, Grove KL, Smith MS. Leptin receptor expression during lactation. Society for the Study of Reproduction 58(suppl 1):96 (abstract #81). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEPO-PROVERA AND BONE DENSITY IN PREMENOPAUSAL WOMEN Principal Investigator & Institution: Clark, M Kathleen.; Associate Professor; None; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: (Adapted from abstract): Registered nurses (RNs) and advanced practice nurses (APNs) play an important role in providing contraceptive services to women of reproductive age. Education and counseling regarding use, risks, and benefits of contraceptive choices are long-standing nursing interventions. With prescriptive authority, APNs are additionally responsible for providing safe, effective pharmacological interventions for preventing pregnancy. DMPA is a progestin only injectable contraception, approved for use in the US in 1992. Of concern is a potential adverse effect of DMPA on bone mineral density. Because DMPA disrupts the hypothalamic-pituitary-ovarian-axis (HPO), it theoretically will suppress estrogen production causing a relative estrogen deficiency, and corresponding loss of bone mineral density. The overall goals of this study are to determine the effect of DMPA on bone mineral density in women aged 18 to 30 years and to determine whether the effect can be modified by calcium intake or predicted by, baseline estradiol levels, irregular vaginal bleeding or weight gain. A two-year prospective longitudinal study of 275 women, 160 who are receiving their first DMPA injection, and 115 control subjects who are not using any hormonal method of contraception, will be completed. All participants will receive a baseline evaluation, and follow-up evaluations every three months for two years. At baseline, participants will have their bone mineral density of the femoral neck, lumbar spine and total body measured using dual energy x-ray densitometry (DEXA). Blood will be drawn for estradiol levels and other physical measurements completed. Participants will complete nutritional and physical activity assessments, as well as a comprehensive interview detailing demographic, medical reproductive and lifestyle behaviors that may influence bone mineral density. All participants will be given one 90-day menstrual calendar for the daily recording of vaginal bleeding. At each followup evaluation bone mineral density and body composition will be measured, nutrition and physical activity reassessed and components of the interview updated. The menstrual calendar will be collected, reviewed and new calendars provided. Random coefficient regression (RCR) analysis will be the major analytic strategy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETERMINANTS OF BONE HEALTH IN YOUNG GYMNASTS Principal Investigator & Institution: Lewis, Richard D.; Foods and Nutrition; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: There is concern that child participation in artistic gymnastics training has adverse consequences on growth and development. While there is a widespread notion that gymnastics participation is linked to poor diets, disordered eating, secondary

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amenorrhea, and bone loss, the scientific evidence supporting this contention is lacking. Despite low calcium, energy restricted diets and a history of menstrual disruptions, college gymnasts have higher bone mineral density (BMD) than controls. Elevated BMD in premenstrual gymnasts suggests that early gymnastics training, prior to the onset of puberty, is critical in the development of peak bone mass. However, it is possible the enhanced BMD exists before training ever begins. The investigator's main hypothesis is that high-levels of artistic gymnastics training initiated at a young age will enhance BMD. A second hypothesis is that high-levels of artistic gymnastics training initiated at a young age will not promote energy restriction, low calcium intakes or relevant psychological symptoms of disordered eating. There is also concern that gymnastics participation results in a reduced height. A reduction in predicted height and growth velocity and lower insulin-like growth factor 1(IGF-1) levels have been found in gymnasts. However, no studies have examined IGF-1 in gymnasts over time, nor have simultaneous changes in height and growth factors been examined in gymnasts. In addition, no studies have determined whether growth factor levels in gymnasts are lower than nongymnasts prior to the onset of training. A third hypothesis is that highlevels of artistic a gymnastics training initiated at a young age will blunt growth velocity and alter IGF-1 and IGF-1 binding protein-3 (IGFBP-3). To test these hypotheses, girls (58 years of age) will be examined during their first two years of gymnastics training. The specific objectives of the proposal are: 1) to determine if elevated BMD is present before gymnastics training is initiated; 2) to determine the impact of early gymnastics training on BMD, dietary intakes and relevant psychological symptoms of disordered eating behavior; 3) to determine the basis for elevated BMD in gymnasts by assessing growth factors, markers of bone turnover and sexual maturation; and 4) to determine if two years of gymnastics training will blunt growth velocity or alter growth factors. This study will provide insight into the impact of gymnastics activity initiated at an early age on bone and growth in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOCRINE FUNCTION AND MOOD IN BIPOLAR DISORDER Principal Investigator & Institution: Rasgon, Natalie L.; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2004; Project Start 21-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): This is a revised application for an R01 grant: "Reproductive endocrine function and mood in women with bipolar disorder." We will evaluate reproductive endocrine function in women treated for bipolar disorder (BPD). We have collected pilot data, which suggest that women with BPD have an increased frequency of menstrual and metabolic dysfunction. Using a cross-sectional design, this study will prospectively evaluate reproductive endocrine function and mood for three consecutive menstrual cycles in 60 women (ages 20-35) treated for bipolar disorder with standard medications compared to 30 age- and BMI-matched healthy controls. The latter of which may affect menstrual function. Subjects will receive psychiatric evaluation, physical examination and hormonal screening. We will monitor medication effects on both reproductive endocrine function and mood by utilizing ChronoRecord software for daily self-reporting. In addition, we will assess the impact of current medication status (e.g. intake of mood stabilizers and atypical antipsychotics) on reproductive function. This project will expand current knowledge of reproductive biology in women with bipolar disorder by: (1) determining the frequency of reproductive dysfunction in women with BPD compared to healthy controls; (2) identifying predictors for

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reproductive dysfunction; and (3) developing guidelines to minimize potential adverse effects on the reproductive health of women treated for BPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTABLISHING THE GENETIC ETIOLOGY FOR KALLMANN SYNDROME Principal Investigator & Institution: Seminara, Stephanie B.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): In all mammalian species, gonadotropin-releasing hormone (GnRH) is the first hormone in a complex reproductive cascade. GnRH is released by the hypothalamus and stimulates the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary; these gonadotropins then stimulate the gonads to produce sex steroids and follicles/sperm. The actions of GnRH are complex--it is secreted in a pulsatile, as opposed to constitutive, fashion, and at variable frequencies throughout the reproductive cycle. Understanding what signals modulate the developmental fate and secretory actions of GnRH neurons remains a major question for reproductive biologists. This grant proposal will address this issue using a human disease model in which GnRH secretion is defective or absent. Patients with this condition, idiopathic hypogonadotropic hypogonadism (IHH), fail to undergo puberty and are infertile if untreated. Although congenital IHH is a rare disease and family sizes are typically small, a large inbred family of French Canadian descent has been identified with IHH and anosmia. A genome wide scan has been performed and a chromosomal locus for the genetic defect has been identified. In this proposal, the candidate region will be further refined, a complete transcript map for the region will be developed, and RT-PCR will be used to screen the candidate gene for the precise genetic mutation. The mutation spectrum will then be juxtaposed against the baseline clinical/biochemical features of the patients, their neuroendocrine phenotypes, as well as their responses to physiologic replacement with exogenous pulsatile GnRH to develop robust genotype/phenotype correlations. The spatiotemporal pattern of expression of the gene will be studied and in vitro model systems developed to study the physiology of the newly-identified gene. It is hoped that this information will ultimately be used to understand numerous human diseases defined by abnormalities in GnRH secretion, including constitutional delay of puberty, hypothalamic amenorrhea, and central precocious puberty. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN NEGATIVE LACTATIONAL AMENORRHEA

FEEDBACK

IN

POSTPARTUM

Principal Investigator & Institution: Veldhuis, Johannes D.; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FETAL ALCOHOL EXPOSURE AND REPRODUCTIVE DEFICITS Principal Investigator & Institution: Handa, Robert J.; Professor; Anatomy and Neurobiology; Colorado State University Fort Collins, Co 80523

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Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 29-FEB-2004 Summary: (Adapted from the Investigator's Abstract) The reproductive neuroendocrine axis of the female undergoes well described age-related changes which result in the loss of cyclicity during middle age. We have recently shown that adult females exposed to ethanol while in utero exhibit regular estrous cyclicity following puberty but become acyclic at a much earlier age than control females. Studies in this rat model have demonstrated that fetal exposure to ethanol will disrupt the hypothalamo-pituitarygonadal axis of the adult female. Adult fetal alcohol exposed (FAE) females exhibit a delay in the onset of puberty, reductions in the preovulatory-like surge of anterior pituitary gonadotropic hormones, reductions in anterior pituitary gonadotropin subunit mRNAs and reductions in gonadotropin-releasing hormone mRNA in a specific population of neurons in the basal forebrain. These data demonstrate that the young adult FAE female exhibits neuroendocrine impairments which can limit reproductive potential. Many of the neuroendocrine changes in young adult FAE females are similar to those described for the normal middle-aged female rat immediately prior to the onset of age-related anovulatory sterility. Thus, it appears that the FAE female is at increased risk to enter reproductive senescence at an early age. The elucidation of the consequences of fetal alcohol exposure on reproductive hormone secretion supports the possibility of a heightened risk of an early age-related loss of cyclicity in adult human female populations, not limited to those diagnosed with fetal alcohol syndrome, but including populations exposed to much more modest levels of ethanol in utero. In this proposal, we outline studies to investigate the neuroendocrine mechanisms which underlie the deficits in hypothalamo-pituitary-gonadal function and the early onset of anovulatory sterility in the adult female rat exposed to alcohol in utero. We hypothesize that hormone secretion in adult FAE females is impaired due to the decrease in hypothalamic release of gonadotropin-releasing hormone. This is a consequence of the loss of neural systems driving GnRH synthesis or secretion. The long-term goals of these studies are to define the neuroendocrine mechanisms which regulate age-related reproductive deficits in adult females especially in terms of those which are susceptible to damage by prenatal exposure to teratogenic agents such as alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAERGIC CONTROL OF LHRH NEURONAL FUNCTION Principal Investigator & Institution: Ojeda, Sergio R.; Scientist/Division Head; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: Gamma aminobutyric acid (GABA), the dominant inhibitory neurotransmitter in the central nervous system plays a prominent role in the control of hypothalamic LHRH secretion. It now appears that a GABAergic control exerted via GABA/A receptors (GABA-AR) is established during early LHRH neuronal development and continues to operate throughout the natural history of the LHRH neuronal network. It is likely that part of this regulatory influence is exerted directly on LHRH neurons, as they express all of the receptor subunits required for the assembly of functional GABA-AR. Although recent studies have demonstrated a modulatory effect of GABA-AR activation on LHRH neuronal migration, it is not known if such an effect is directly exerted on LHRH neurons. Likewise, nothing is known about the physiological impact that the GABAergic innervation on LHRH neurons may have on the control of adult reproductive function. Resolution of these issues by conventional neuroendocrine experimentation is difficult, because of the intricacy of the neuronal circuities affected by GABA and the molecular complexity of the GABA-AR system. The recent development

18

Amenorrhea

of genetic approaches to modify the expression of genes in a cell-specific and temporally- restricted manner, and the identification of some of the key components involved in GABA-AR-mediated signaling, provide us with a unique opportunity to unravel some of the basic mechanisms underlying the GABAergic control of reproductive function. In this study, we propose a combination of genetic and neuroendocrine approaches to define the contribution of GABA to the embryonic development of LHRH neurons and to the functional competencies of the LHRH neuronal network during adulthood. To this end, the following aims are proposed to test the hypotheses that: 1) Direct GABAergic excitatory inputs play a role in the migration and developmental rate of LHRH neurons. 2) The direct GABA-AR-mediated input received by adult LHRH neurons is a regulatory component of the LHRH neuronal network required for normal reproductive cyclicity. 3) Selective disruption of the GABA-AR beta/3 subunit in LHRH neurons results in hypothalamic hypogonadism, and 4) A site- and time- specific, reversible activation of GABA release suffices to disrupt menstrual cyclicity in non-human primates, thus re-creating in an experimental setting the human syndrome of hypothalamic amenorrhea. We anticipate that these studies will lead to a better understanding of the cellular mechanisms underlying the central loss of reproductive competence in human syndromes such as hypothalamic amenorrhea and idiopathic hypothalamic hypogonadism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER DIFFERENCES IN DRUG ABUSE Principal Investigator & Institution: Becker, Jill B.; Professor; Psychology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAY-2003 Summary: The experiments proposed will utilize well characterized animal models to study the neurobiological basis for gender differences in drug abuse. Neuroadaptations associated with sensitization to psychomotor stimulants are thought to play an important role in the process of addiction. Furthermore, gender differences in the behavioral and neurochemica1 effects of psychomotor stimulants have been repeatedly reported to occur in rodents, and more recently in humans as well. In order to begin to understand gender differences in drug abuse, we believe that basic research on the role of gender and ovarian hormones in the response to acute and repeated exposure to cocaine is an important next step. Research on the acute behavioral response to psychomotor stimulants indicates that treatment of female rats with the ovarian hormone estrogen is sufficient to induce changes comparable to the effects of the estrous cycle. There are two hypotheses to be tested. The first is that there are gender differences in behavior induced by repeated exposure to the psychomotor stimulants and gender differences in self-administration of cocaine. The second is that estrogen potentiates both the acute and sensitized response to cocaine in female rats, enhancing these gender differences. In order to begin to understand the underlying neurological bases for gender differences in cocaine addiction there are two important factors that must be teased apart: l) differences between males and females (independent of gonadal hormones); and 2) whether gonadal hormones in either males or females affect responses to cocaine. In humans these factors are intermingled because chronic cocaine use can disrupt and even cause cessation of a woman's menstrual cycle. In such women, estrogen may play a role in acquisition of drug taking behaviors, but not in maintenance of these behaviors (since in women with amenorrhea the serum concentrations of estrogen are extremely low). On the other hand, more men than women abuse drugs, and many boys begin using drugs prior to sexual maturation. The experiments

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proposed will allow us to tease apart the relative importance of gender vs gonadal hormones in animal studies investigating the effects on cocaine-induced psychomotor behavior and cocaine self-administration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GNRH INHIBITION IN ANOREXIA NERVOSA Principal Investigator & Institution: Warren, Michelle P.; Associate Professor; Obstetrics and Gynecology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 08-MAR-2000; Project End 28-FEB-2004 Summary: It is well known that the gonadotropin-releasing hormone (GnRH) pulse generator is highly sensitive to environmental insults, particularly weight loss and low body fat and we propose that the modulation of GnRH is mediated by a leptinmetabolic axis. Anorexia nervosa in young women is associated with severe weight loss, amenorrhea and a leptin deficient state, which reverses with weight gain. This problem appears to be due to a hypothalamic dysfunction affecting GnRH pulsatility. Those who do not experience a reversal generally demonstrate disordered eating. The calorically depressed state of anorexia nervosa is also associated with a decrease in resting metabolic rate (RMR). Recent work on obesity suggests that the RMR may remain depressed in individuals who maintain a body weight that is lower than their 'normal' weight. This continues to be a problem with recovered anorectics. We hypothesize that anorexia nervosa and associated disordered eating are closely tied to a depressed RMR and a metabolic cascade reflecting inadequate metabolic resources which influences the secretion of leptin and the expression of GnRH. An increase in the RMR will be associated with a return of normal leptin levels and GnRH function, resulting eventually in normal cyclicity. We propose that those who continue to experience amenorrhea will continue to have low RMR, low leptin levels and manifest disordered eating. A detailed study of young women with anorexia nervosa and their patterns of disordered eating serve as a perfect model to investigate the link between nutrition, leptin, RMR and the neuroendocrine and ovarian axes. This study will measure RMR using a unique state of the art chamber, changes in reproductive hormones and leptin levels, GnRH pulsatility (LH and FSH pulse studies), responses to GnRH and leptin and cortisol pulses in women receiving treatment for anorexia nervosa. Thirty-six patients and fourteen controls will be followed with adrenal hormone profiles, hormonal markers of nutritional intake, body composition and eating disorder profiles. Data will be obtained before and after a refeeding protocol which brings patients to 90% of ideal body weight, and at six month intervals for a follow-up period of 1 year. Understanding the dysfunction seen in anorexia nervosa could provide a key to the long sought metabolic signal involved in GnRH pulsatility, an important central mechanism in the reproductive cycle of women, as well as open up new avenues for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPROVING PDC/MWRI INSTITUTIONAL ANIMAL RESOURCES Principal Investigator & Institution: Schatten, Gerald P.; Professor; Magee-Women's Health Corporation 204 Craft Ave Pittsburgh, Pa 15213 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 14-SEP-2004 Summary: (provided by applicant): The MWRI is a multidisciplinary research institute dedicated to women and infants' health. The majority of its 70 members are from three Departments of the Medical School of the University of Pittsburgh: Obstetrics, Gynecology, and Reproductive Sciences; Pediatrics; and Pathology. The remaining

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members of the Institute are from other departments in the Medical, Nursing, and Pharmacy Schools and from the Graduate School of Public Health of the University of Pittsburgh. Membership includes investigators with M.D., Ph.D. or both, who have expertise in clinical or basic research as well as epidemiology or health services research. The Institute emphasizes research and training in interactive, innovative, and translational research. On-going projects include studies in amenorrhea, pre-eclampsia, pregnancy loss, and sexually transmitted diseases. Currently, the investigators of the MWRI utilize mice, rats, and non-human primates as animal models of human disease. The PDC of the MWRI is actively researching contemporary topics of national importance including: the pluripotency of embryonic stem cells using non-human primates; the feasibility of a variety of transgenic approaches for disease modeling using primates; the outcome of Assisted Reproductive Technologies (ART) in macaque models; and the feasibility of cloning in non-human primates, either for production of identical research models or to evaluate 'therapeutic' cloning. All the non-human primate research performed at the MWRI is performed under the auspices of the PDC. This application requests funds to: 1) provide the PDC and MWRI vivarium with stateof-the-art non-human primate enclosures that exceed all new United States Department of Agriculture (USDA) directives for psychological enrichment; and 2) modernize the PDC and MWRI vivarium with a steam sterilizer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN RESISTANCE AND POLYCYSTIC OVARY SYNDROME Principal Investigator & Institution: Brown, Ann J.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This career development proposal details a plan for the Principal Investigator to obtain the training and experience necessary to develop an independent career as a clinical investigator. By conducting the proposed study, the PI will develop skills that will enable her to study the effects of exercise on insulin resistance in polycystic ovary syndrome (PCOS), and that will be relevant to many career pathways. PCOS is a common disorder affecting up to 10% of young women. It is characterized clinically by hirsutism and oligo/amenorrhea. Recent studies have documented significant insulin resistance in this population suggesting an important predisposition to long-term complications such as diabetes and cardiovascular disease. The early onset and large affected population create a powerful opportunity to harness the positive effects of lifestyle changes for purposes of disease prevention. However, the hirsutism and obesity associated with PCOS may create psychological barriers to change. For this reason, effective management may require a tailored approach that takes into account psychosocial issues as well as metabolic profile. Physical activity is an ideal intervention for this group. Exercise reduces insulin resistance, improves cardiovascular health and enhances sense of wellbeing. However, the type, duration and intensity of exercise that will optimally reduce insulin resistance, and that is well tolerated, has not been established. This study is meant to address these issues by answering the following questions about women with PCOS: 1. In a randomized controlled clinical trial, does a 12 week program of monitored exercise of moderate intensity, without weight loss, significantly improve insulin sensitivity as measured by an intravenous glucose tolerance test? What is the relative magnitude of the acute effect compared to the chronic effect of exercise on insulin sensitivity? 2. Does exercise that reduces insulin resistance also decrease androgen levels? 3. Does exercise improve indicators of perceived body image, quality of life, stress and depression?

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

Project Title: INSULIN SIGNALING IN THECA CELLS FROM POLYCYSTIC OVARIES Principal Investigator & Institution: Magoffin, Denis A.; Professor; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 21-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disease in women of reproductive age. Approximately three-quarters of women with anovulatory infertility have PCOS, thus accounting for approximately one-third of women with secondary amenorrhea and approximately 90% of women with oligomenorrhea. Other consequences of PCOS are hirsutism, markedly increased incidence of recurrent early pregnancy loss, an estimated 11-fold increased risk of myocardial infarction between the ages of 50-61 years, and an increased risk of endometrial cancer at a young age. A consistent finding in women with PCOS is that the ovaries produce abnormally high amounts of androgens. There is good evidence to conclude that elevated androgens interfere with selection of dominant follicles and cause PCOS. Importantly, there is an association between insulin resistance and the androgen excess of PCOS. It is clear that insulin can stimulate ovarian androgen production, but a paradox exists: how can insulin hyperstimulate ovarian thecal androgen production in an insulin resistant woman? One of two hypotheses could explain the seeming paradox. Either the ovarian theca cells are not insulin resistant in insulin resistant women or there are distinct insulin signaling mechanisms regulating glucose metabolism and androgen production in theca cells. The purpose of the proposed studies is to determine if ovarian theca cells are insulin resistant in insulin resistant women, to explore the intracellular signaling mechanisms by which insulin regulates androgen biosynthesis, and to determine if there are differences in the concentrations and/or activities of key molecules mediating insulin action in theca cell from polycystic ovaries. To accomplish these goals, we will measure the sensitivity of skeletal muscle and ovarian theca cell glucose uptake in response to insulin to determine the relative sensitivity of these tissues to insulin in insulin sensitive and insulin resistant women with and without PCOS. We have established a human theca cell culture model in which we can examine the molecular details of insulin signaling. Importantly, increased androgen production and steroidogenic enzyme mRNA over-expression persist in the cultured cells in vitro. We propose to use this model to systematically determine the intracellular signaling pathway for insulin stimulation of CYP 17 activities and mRNA expression and then to compare the concentrations and activities of the signaling molecules between regularly cycling control women and women with PCOS. The results of these studies are expected to yield specific molecular targets for novel therapies to treat women with PCOS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LEPTIN IN NEUROENDOCRINE FUNCTION Principal Investigator & Institution: Chan, Jean L.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2009 Summary: (provided by applicant): This K23 proposal on the role of leptin in neuroendocrine function and the treatment of HA combines a rigorous research agenda, close personal mentoring, and coursework tailored to train Dr. Jean L. Chan as an

22

Amenorrhea

independent clinical investigator. Dr. Chan is currently a third-year fellow in Endocrinology and Metabolism who has an interest in human leptin physiology and treatment studies and has recently completed the first interventional study to evaluate the role of leptin in the neuroendocrine and immune response to fasting in healthy lean men - a subject of profound physiologic interest with substantial clinical relevance and significance for both high-leptin and low-leptin states. She is also currently enrolled at Harvard Medical School in the Clinical Scholar's program designed to train postdoctoral fellows in clinical investigation. For the K23 proposal, she intends to evaluate whether a threshold level of leptin is of importance in the neuroendocrine response to fasting by studying obese leptin-resistant men and whether gender has an effect on this response by studying women, who have different leptin physiology from men. The study design will involve double-blind, randomized, placebo-controlled fasting studies with leptin administration. This research may elucidate the compensatory neuroendocrine mechanisms responsible for the plateauing effect of caloric restriction in the treatment of obesity and contribute to our understanding of the neuroendocrine abnormalities associated with eating disorders. This proposal will also evaluate leptin as a potential treatment to restore menstrual cycles in women with HA, a low-leptin state associated with abnormalities in GnRH pulsatility as well as other neuroendocrine axes and bone metabolism. Dr. Chan is currently conducting a pilot study to evaluate the feasibility of this hypothesis and will use a larger, placebo-controlled study design with leptin administration for the K23 proposal. Dr. Christos Mantzoros, an established expert and leader in the leptin field, will be Dr. Chan's mentor. The Clinical Scholars program will encompass a thesis-level research effort, and Dr. Chan has assembled a thesis committee who is monitoring and guiding her progress. She will also have the opportunity to take advanced biostatistics classes at Harvard Public Health School. The proposed research will not only provide critically important and novel scientific information in the area of leptin physiology in humans but it will serve as the foundation for developing new avenues of future research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEPTIN IN THE NEUROENDOCRINE RESPONSE TO FASTING Principal Investigator & Institution: Shetty, Greeshma K.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2004; Project Start 01-JUL-2005 Summary: (provided by applicant): This study will improve our understanding of the normal physiology of leptin's secretion and its role in the neuroendocrine response to starvation in women. It has significant clinical implications for two states in particular: 1) low leptin states, such as anorexia or exercise induced amenorrhea, in which leptin administration may correct or decrease the hormonal and metabolic derangements and 2) high leptin states, such as obesity, which are treated with hypocaloric diets and may also benefit from leptin administration by permitting maintenance of weight loss and blocking intrinsic metabolic efforts to maintain a positive energy homeostasis. Hence, this study will elucidate the pathophysiology and may provide the basis for successful therapeutic options for these states. This study will have a placebo-controlled design. The subjects will be evaluated three times: once in the fed state, once in the fasted with leptin and once in the fasted with placebo. It is impossible to blind subjects and investigators regarding the studies in the fed state, but the two studies in the fasted state will be performed in a double-blinded randomized fashion. Each GCRC admission will be 4 days and will require blood and urine collection. Please see the research-training proposal in section FF for further details.

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

Project Title: LEPTIN, ENERGY BALANCE & REPRODUCTION Principal Investigator & Institution: Kasa-Vubu, Josephine Z.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BLEEDING

MIFEPRISTONE

FOR

PREVENTION

OF

BREAKTHROUGH

Principal Investigator & Institution: Jain, John K.; Assistant Professor; ObstetricsGynecology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Progestin-only contraceptives such as depomedroxyprogesterone acetate (DMPA) represent one of the most effective classes of contraceptives but are limited by high discontinuation rates due to breakthrough bleeding especially during the first year of use. Mifepristone is a competitive progesterone receptor antagonist. When Mifepristone was given to normally cycling primates, a near-amenorrheic state was achieved. Mifepristone has been shown to decrease breakthrough bleeding in women using levonorgestrel implants. Although estrogen receptor expression increases after Mifepristone administration, a paradoxical anti-proliferative effect is seen in the endometrium. That has lead some investigators to conclude that mifeprisone can suppress estrogen receptor transcriptional activity through non-competitive means such as sequestration of estrogen receptor transcriptional cofactors. The result being lack of endometrial proliferation and development of an atrophic endometrial state. With less endometrial tissue to shed, bleeding diminishes and amenorrhea ensues. We propose to conduct a 14-month prospective, randomized, double-blind, placebo-controlled study of 50 mg of Mifepristone administered every 2 weeks for 12 cycles to 50 new starters of DMPA in order to determine the incidence of bleeding and ovulation. Bleeding data will be gathered with the use of daily dairies and ovulation monitored by thrice-weekly urine collections. Seven endometrial biopsies obtained pre- and post - treatment will be analyzed using immunohistochemical and quantitative RT-PCR methods to evaluate levels of estrogen and progesterone receptor isoforms. Biopsies will also be evaluated histologically. In order to determine the function of estrogen receptors following DMPA and Mifepristone we will establish primary endometrial cell culture and test estrogen function by measuring markers of proliferation such as SRC, MIB-1 and MMT and correlating results to in vivo biopsy samples. We are currently conducting a pilot study similar to the one proposed to gather preliminary data and to test the feasability of a larger trial. If Mifepristone is shown to safely decrease the incidence of breakthrough bleeding, more women may continue DMPA and not place themselves at risk of an unintended pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR DYNAMICS OF GONADOTROPINS Principal Investigator & Institution: Lin, Yu-Wai P.; Barry University 11300 Ne 2Nd Ave Miami, Fl 331616695

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Amenorrhea

Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROENDOCRINE REGULATION OF GNRH RELEASE Principal Investigator & Institution: Levine, Jon E.; Professor; Neurobiology and Physiology; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 01-MAR-1996; Project End 31-MAR-2007 Summary: (provided by the applicant) The nervous system regulates the reproductive axis through the activity of the "GnRH pulse generator," neurons in the hypothalamus whose activity governs pulsatile release of gonadotropin-releasing hormone (GnRH). The amplitude and frequency of GnRH pulses are, in turn, regulated by physiological signals, some of which evoke sustained shifts in the activity of the GnRH pulse generator and hence, in overall reproductive state. Metabolic cues, for example, are clearly important for maintenance of GnRH pulsatility in adult animals, and in the deceleration of GnRH pulsatility that occurs under conditions of negative energy balance. Cellular and molecular mechanisms mediating physiological shifts in GnRH pulse generator activity remain unknown. These studies will test the hypothesis that metabolically-linked adjustments of GnRH pulse generator activity are mediated by regulation of ion channels, specifically those known to link cell metabolism to cell excitability - the ATP-sensitive potassium channels (K+ATP channels). The K+ATP channel closes upon binding AlP, leading to reduced cellular K+ permeability, membrane depolarization and thus, increased cell excitability; reduced intracellular ATP produces the opposite conditions, reducing cell excitability. Preliminary work implicates hypothalamic K+ATP channels activity in the modulatation of GnRH release. The proposed studies are therefore designed to determine whether K+ATP channel opening and closing in vivo lead to alterations in GnRH pulse generator activity (Aim 1), assess whether opening of K+ATP channels mediates inhibition of GnRH pulsatility during food-restriction (Aim 2), determine the molecular and functional properties of KATP channels in identified GnRH neurons [Aims 3,4], and determine whether suppression of hypothalamic K+ATP channel expression reverses effects of negative energy balance on GnRH pulsatility (Aim5) A transgenic mouse will also be developed (Aim 6) in which expressesion of overactive (open) K+ATP channel subunits will be targeted to GnRH neurons, permitting examination of the reproductive consequences of K+ATP channel hyperactivity in GnRH neurons. These studies may provide new and important information on cellular mechanisms mediating many major physiological alterations in GnRH pulse generator activity. They may also permit an understanding of how GnRH pulse generation is inhibited in feeding disorders such as anorexia nervosa, or in other hypogonadotropic states, such as functional hypothalamic amenorrhea associated with subclinical eating disorders or rigorous exercise training. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROENDOCRINOLOGY OF PUBERTY Principal Investigator & Institution: Foster, Douglas L.; Professor & Research Scientist; Obstetrics and Gynecology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-MAR-1984; Project End 31-JAN-2005 Summary: When nourishment is inadequate or energy expenditure is great, fertility is reduced in the adult, and puberty is delayed in the developing individual. This

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suppression of reproductive activity is not understood mechanistically. We believe this to be an integrative problem at this stage of inquiry that requires both physiologic and pharmacologic approaches to answer broad questions about how the brain discriminates how well nourished and how mature the body is. Our broad objective is to understand the physiological mechanisms by which changes in nutrition and metabolism control reproduction, specifically the signals, sensors, and pathways whereby blood-borne information regulates GnRH secretion. To progress further in understanding the relationship between growth, metabolism and production of high frequency GnRH pulses during development, we must first determine how energy metabolism regulates GnRH secretion. To progress further in understanding the relationship between growth , metabolism and production of high frequency GnRH pulses during development, we must first determine how energy metabolism regulates GnRH secretion in the adult. Thus, we will first evaluate how changes in glucose availability and leptin modify GnRH secretion during adulthood and then determine if such a mechanism might be timing puberty during growth. The sheep will be used because its large size and long lifespan permits individuals to be studied longitudinally through their development and permits detailed studies in adults. Importantly, it is well suited for the characterization of hypophysiotrophic hormone patterns. Specific Aim 1 will determine if the hindbrain and the liver contain sensors that transmit information about glucose availability to regulated GnRH secretion. We will both increase and decrease availability locally in each site to establish their function and their interrelationships. Specific Aim 2 will determine the role of leptin as a signal to regulate the pulsatile secretion of GnRH. This will be achieved through central administration of leptin during both acute fasting and chronic low nutrition. Although widely studied in feeding behavior, we have little understanding of its physiologic role in regulating GnRH secretion. Specific Aim 3 will assess "nutritional stress" as a cause hypogonadotropism through reduced GnRH secretion by monitoring of stress peptides in the pituitary portal circulation and by antagonizing their action during acute fasting and chronic low nutrition. Specific Aim 4 will determine if glucose availability times the pubertal GnRH increase by using the power of our large animal model in which we can chronically administer metabolically important signals such as insulin and leptin. Understanding the metabolic control of GnRH secretion has broad application both to growth and maturation and to other physiologic conditions in which reduced GnRH secretion may contribute to infertility because of altered energy metabolism. These include dietary malnutrition from eating disorders; during high-energy expenditure, as in exercise- induced amenorrhea and lactational anovulation; during type 1-diabetesinduced infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORGANOPHOSPHATE REPRODUCTIVE HEALTH

PESTICIDES

AND

HUMAN

Principal Investigator & Institution: Xu, Xiping; Associate Professor & Director; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from the Investigator's Abstract) This study is designed to recruit and prospectively follow a cohort of women and their husbands to assess the effects of exposure to organophosphate (OP) pesticides on adverse reproductive outcomes in both men and women in agricultural workers. Married never-smoking women age 20-34 who currently work in Haikou Township, Anqing, who have obtained permission to have a

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child, and who will be attempting to become pregnant over the course of the study will be eligible for the study. Reproductive endpoints will include (1) semen parameters (concentration, total count, motility, progression and morphology), (2) menstrual disorders (oligomenorrhea, amenorrhea, polymenorrhea, intermenstrual bleeding, prolonged menstrual bleeding, dysmenorrhea, and irregular menstruation); (3) alterations in hormone patterns including reduced estrogen excretion (REE), anovulation, abnormal luteal phase (ALP), and abnormal follicular phase (AFP) in women and abnormalities of LH, FSH, TSH, SHBG, inhibin-B and testosterone in men; (4) fecundability; and (5) pregnancy outcomes including spontaneous abortion, preterm delivery, low birth weight and intrauterine growth retardation. After enrollment, interviewers will administer a previously validated questionnaire to the women and their husbands to collect baseline information on sociodemographic, environmental, occupational, and personal covariates. Semen samples will be obtained by trained technicians at enrollment and again four months later. Each woman will keep a diary of her menstrual information, environmental exposures, and dietary intake. Daily urine samples will be collected from each female subject for up to one year or until a pregnancy occurs. Urinary PdG, EIC, LH, FSH and hCG will be measured to identify abnormal endocrine patterns and subclinical pregnancy. Once a woman becomes pregnant, she will be followed for pregnancy outcomes obtained from a follow-up survey and hospital records where the baby is delivered. Extensive exposure assessment will be conducted throughout the follow-up period and, therefore, dose-response relationships can be established. All participants will keep daily exposure diaries. Urine samples will be measured for metabolites on selected exposure days. A subset of participants will be studied for personal air monitoring and serial analysis of urine metabolites to validate the exposure diary and urine metabolite assay. The investigators state that the proposed study has several strengths: (1) it will be conducted in a population with a broad range of organophosphate pesticide exposure; (2) exposure will be well-characterized; (3) each woman and her husband will be studied simultaneously; (4) the prospective study design can eliminate certain flaws or potential biases in previous retrospective studies; (5) time to conception and spontaneous abortion will be evaluated with the improved specific hCG assay, which can detect pregnancy within a few days of implantation; (6) recently-developed biomarkers, including urinary hormone assays and FISH methods, will be applied to the study; (7) gene-environment interactions will be tested; (8) the field cost in China is much lower than that in the U.S.; and (9) the population possesses unique characteristics for examining the proposed hypothesis, i.e., a stable workforce, a non-smoking group and excellent compliance rates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORTHO TRI CYCLEN ON BIOCHEM MARKERS OF BONE METAB IN HYPOTHALAMIC AMENORRHEA Principal Investigator & Institution: Miller, Karen K.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AMENORRHEA

PATHOGENESIS

OF

FUNCTIONAL

27

HYPOTHALAMIC

Principal Investigator & Institution: Berga, Sarah L.; Professor and Chair; MageeWomen's Hospital of Upmc 300 Halket St Pittsburgh, Pa 15213 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-APR-2004 Summary: This proposal, "Pathogenesis of Functional Hypothalamic Amenorrhea," is in response to PA-9l-lOO, "Special Issues in Women's Mental Health Over the Life Cycle." Ovulatory dysfunction is the most common cause of infertility in women and functional hypothalamic amenorrhea (FHA) is the most common cause of ovulatory dysfunction. FHA is the cessation of menses in a previously eumenorrheic woman in whom organic causes have been excluded and therefore it is theoretically reversible. A constellation of neuroendocrine secretory disturbances attributable to altered hypothalamic function, including reduced LH pulsatility, have been documented. The proximate cause of FHA is insufficient GnRH secretion. The goal of this proposal is to investigate the genesis of the altered hypothalamic function, particularly the disruption of the GnRH pulse generator, so that targeted interventions can be devised. The overall hypothesis underlying this series of studies is that FHA follows a chronic and/or excessive stress response, so the two main components of the stress system, the CRH neuronal network and the locus ceruleus-norepinephrine/autonomic system, will be examined in humans and monkeys. The following specific hypotheses will be tested: (l) women with FHA have distinct cognitive and psychological characteristics that are likely to predispose to activation of the stress systems; (2) women with FHA are more reactive to behavioral challenge; (3) central neuronal systems that regulate hypothalamic function (as assessed by CSF levels) are altered in women with FHA; (4) social stress induces FHA and a constellation of neuroendocrine disturbances in monkeys similar to those seen in women with FHA; (5) pharmacological blockade of the central neuronal systems activated by social stress in monkeys prevents FHA; (6) monkeys become sensitized to repetitive social stress with regard to the development of FHA. With regard to refining our model of the pathogenesis of FHA, the monkey studies are critical to identifying causality and pharmacologic agents, while the human studies are integral to devising targeted psychosocial and/or pharmacologic interventions. We expect that the results of this proposal will lead directly to the PA-91-lOO objective of developing a "psychosocial intervention for infertility." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AMENORRHEA

PATHOGENESIS

OF

FUNCTIONAL

HYPOTHALAMIC

Principal Investigator & Institution: Cameron, Judy L.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: The overall goal of this grant is to increase our understanding of the etiology of Functional Hypothalamic Amenorrhea (FHA) and to test several novel treatment regimens for this reproductive disorder. Anovulation is the most common cause of infertility in women and FHA is the most common cause of anovulation. The proximate cause of FHA is insufficient hypothalamic gonadotropin-releasing hormone (GnRH) secretion. However, a constellation of neuroendocrine secretory disturbances attributable to altered hypothalamic function exist. Our current investigation in women and in monkeys implicates dysfunctional attitudes, psychosocial stress, and associated behaviors such as calorie restriction and exercise in the genesis of characteristic

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Amenorrhea

hypothalamic-pituitary-adrenal (HPA), HP-thyroidal (HPT), and HP-ovarian (HPO) secretory alterations. Thus, we conceptualize FHA as a state of altered hypothalamic homeostasis caused by synergism between psychogenic challenge and meta boli c compromise. Building on these findings, we hypothesize that cognitive behavior therapy (CBT) aimed at improving attitudes and correcting problematic behaviors will reverse hypothalamic derangements and restore ovulation. One aim of this grant is to test this hypothesis. However, because not all women with FHA will respond to CBT, we are continuing our quest to discern in women and in monkeys the neurobiological mechanisms underlying the synergism between psychogenic and metabolic stressors with the goal of identifying promising pharmacologic interventions. To refine our model of the pathogenesis of FHA, monkey studies are critical to identifying causality and pharmacologic options, while the human studies are integral to testing the efficacy of psychosocial and pharmacologic therapies. An interdisciplinary team of established investigators is working on these combined clinical and basic studies, with expertise in the areas of psychiatry, behavioral medicine, exercise physiology, neurobiology, and reproductive endocrinology. New findings this year indicate that monkeys with elevated basal heartrate are more prone to develop stress-induced reproductive dysfunction than monkeys with lower basal heartrate. We are currently examining whether this also holds true for women. FUNDING NIMH MH 50748-05 PUBLICATIONS Cameron JL, Bridges MW, Graham RE, Bench L, Berga SL, Matthews K. Basal heartrate predicts development of reproductive dysfunction in response to psychological stress. In The Endocrine Society Program and Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 138 (abstract #P1-76). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS AS PREDICTORS OF ECTOPIC PREGNANCY Principal Investigator & Institution: Barnhart, Kurt T.; Assistant Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: Ectopic pregnancy (EP) is the leading pregnancy - related cause of death in the first trimester of pregnancy and a major contributor to maternal morbidity. As the tubal pregnancy progresses, it erodes into blood vessels and can cause massive intraabdominal bleeding. There are limitations in the strategies currently employed to diagnose EP. Even with the use of diagnostic algorithms that systematically evaluate all women at risk for an EP, only 50 percent of women with an EP can be diagnosed upon presentation to an Emergency Department (ED). Diagnosis in the remaining 50 percent represents a clinical conundrum and can take up to 6 weeks. If the diagnosis of EP is delayed, the abnormal gestation will continue to grow in the fallopian tube with potential rupture resulting in greater risks of morbidity, and mortality. Moreover, an EP of large size is not amenable to medical therapy, may require major surgery (laparotomy) instead of laparoscopy and can cause greater damage to fallopian tube (and greater impairment of fertility), even if treated before rupture. The aims of this proposal focus on this clinically relevant subpopulation of women at risk for an EP butwhose diagnosis cannot be confirmed during their initial presentation to the ED, and is thus delayed. The University of Pennsylvania Medical Center has used a systematic, validated, protocol to diagnose pregnant women who are at risk for EP since 1989. An existing electronic database chronicles the clinical course and contains the results of the diagnostic tests used to definitively diagnose women at risk for EP but not diagnosed upon presentation to the ED. We plan to use the information in this database to: 1) identify factors predictive of EP in this subgroup of pregnant women and derive a

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clinical prediction rule to help identify those at highest risk for EP in an attempt to shorten the time needed for diagnosis. And 2) to evaluate the serial betahcg determinations to assess the clinical utility defining deviations from the curves characteristic of a viable intrauterine pregnancy (IUP) or spontaneous miscarriage (SAB) to diagnose an EP. For these aims, we will use a retrospective cohort study design of greater than 2100 subjects. We also plan to perform a prospective cohort study, in the same study population to: 3) evaluate the utility of novel strong predictors of EP including the endometrial stripe thickness and chlamydia serology, independently, and in context with the derived prediction rule. And 4) to validate our derived prediction rule using a prospectively collected sample of women at high risk of EP. Finally, we plan for the first time, 5) to investigate if the different clinical situations in which a woman with EP are diagnosed represent differences in the natural history of EP. This proposal represents a unique opportunity to use large amounts of existing data, combined with the efficient prospective collection of data, to understand and improve upon important limitations in our ability to diagnose a reproductive disorder with important public health consequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAFETY AND EFFICACY OF TROGLITAZONE IN POLYCYSTIC OVARIAN SYNDROME Principal Investigator & Institution: Meyer, William R.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFEY AND EFFICACY OF ESTROGEN IN HYPERPROLACTINEMIC AMENORRHEA Principal Investigator & Institution: Schlechte, Janet A.; Professor of Endocrinology and Metabolis; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This study is determining the effects of chronic estrogen administration on tumor size, bone density, serum lipids, and pulsatile prolactin secretion in women with hyperprolactinemic amenorrhea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SECRETORY RESPONSE OF GROWTH HORMONE TO ACUTE EXERCISE IN AMENORRHEIC WOMEN Principal Investigator & Institution: Robergs, Robert A.; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEROTONIN'S ROLE IN PSYCHOBIOLOGY OF ANOREXIA NERVOSA Principal Investigator & Institution: Attia, Evelyn; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 10-FEB-2001; Project End 31-JAN-2006 Summary: Anorexia Nervosa (AN) is a serious psychiatric illness that is characterized by significant weight loss, hormonal disturbance reflected in amenorrhea, and cognitive distortions about body weight and shape. The purpose of this Mentored PatientOriented Research Career Development Award (MPORCDA), is to develop and execute a program of research that will investigate biological disturbances and associated clinical symptoms in women with AN, in order to elucidate some of the factors which may contribute to the development, as well as the high degree of tenacity, of this disorder. Specifically, it will test the hypotheses that 1) normal-weight women with history of AN have higher measures of serotonin, as evidenced by plasma tryptophan levels, and CSF 5-HIAA than age- and weight-matched healthy control women; 2) recently weight-restored women with AN will have lower measures of serotonin and its activity than will long-term weight restored women, as evidenced by plasma tryptophan, CSF 5-HIAA, and tryptophan-depletion challenge; and 3) long-term weight restored women will have evidence of lower serotonin transporter (SERT) binding potential (BP) as measured by PET study, compared with healthy controls, presumably because higher neurochemical levels led to down-regulation of receptor concentration. Under the strong mentorship of individuals with expertise in clinical research training and AN, neuroscience (specifically serotonergic activity and its assessment), and consultation from individuals with expertise in psychobiology of eating disorders, in brain imaging, in biology of eating and feeding behavior, and in the role of serotonin in gastrointestinal function, this MPORCDA will provide the candidate with the skills and further experience to integrate the advances of the fields of anorexia nervosa, neuroscience and biological psychiatry. The long-term goal of this award is for the candidate to become an expert and independent researcher in the psychobiology of eating disorders, with special application to anorexia nervosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOYBEAN DIETS AND BREAST CANCER PREVENTION Principal Investigator & Institution: Lu, Lee-Jane W.; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002 Summary: Soy consumption is associated with reduced risk for breast cancer. However, the phytoestrogens in soy has also been shown to cause adverse reproductive effects such as infertility in sheep but not in every species. Also, weak estrogen such as tamoxifen while effective in preventing breast cancer causes excess risk of endometrial cancer. Before a long term dietary recommendation of soy consumption can be suggested as public health policy, the potential adverse effects of soy consumption needs to be established which is the main goal of this protocol. This study determines if soy consumption can induce amenorrhea in premenopausal women and adverse effect on endometrium of postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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.3 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 amenorrhea, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “amenorrhea” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for amenorrhea (hyperlinks lead to article summaries): •

16-year-old female with amenorrhea. Author(s): Partington MD, Radkowski MA, Tomita T. Source: Pediatric Neurosurgery. 1998 January; 28(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9693330&dopt=Abstract

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A brief review of the effects of chronic hydrocephalus on the gonadotropin releasing hormone system: implications for amenorrhea and precocious puberty. Author(s): Abdolvahabi RM, Mitchell JA, Diaz FG, McAllister JP 2nd. Source: Neurological Research. 2000 January; 22(1): 123-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10672590&dopt=Abstract

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A case of primary amenorrhea, diabetes and anosmia. Author(s): Jenkin A, Renner D, Hahn F, Larsen J. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 February; 14(1): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10813110&dopt=Abstract

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A case study: secondary amenorrhea. Author(s): Cirolia B. Source: Journal of the American Academy of Nurse Practitioners. 1999 January; 11(1): 13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10504917&dopt=Abstract

3 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.

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A complex mosaicism 45,X/46,X,del(Xq)/46,X,idic(Xq) in a patient with secondary amenorrhea. Author(s): Calvano S, de Cillis GP, Croce AI, Perla G, Notarangelo A, Zelante L. Source: Annales De Genetique. 2002 July-September; 45(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381444&dopt=Abstract

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A critical examination of the amenorrhea and weight criteria for diagnosing anorexia nervosa. Author(s): Watson TL, Andersen AE. Source: Acta Psychiatrica Scandinavica. 2003 September; 108(3): 175-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890271&dopt=Abstract

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A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea. Author(s): Kondoh Y, Uemura T, Murase M, Yokoi N, Ishikawa M, Hirahara F. Source: Fertility and Sterility. 2001 October; 76(4): 748-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591409&dopt=Abstract

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A modified hMG-GnRH method for the induction of ovulation in infertile women with severe hypogonadotropic amenorrhea. Author(s): Yokoi N, Uemura T, Murase M, Kondoh Y, Ishikawa M, Hirahara F. Source: Endocrine Journal. 2002 April; 49(2): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081234&dopt=Abstract

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A new clinical option for hormone replacement therapy in women with secondary amenorrhea: effects of cyclic administration of progesterone from the sustainedrelease vaginal gel Crinone (4% and 8%) on endometrial morphologic features and withdrawal bleeding. Author(s): Warren MP, Biller BM, Shangold MM. Source: American Journal of Obstetrics and Gynecology. 1999 January; 180(1 Pt 1): 42-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9914576&dopt=Abstract

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A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Author(s): Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. Source: Fertility and Sterility. 2002 January; 77(1): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779596&dopt=Abstract

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A review of the female athlete triad (amenorrhea, osteoporosis and disordered eating). Author(s): Golden NH. Source: Int J Adolesc Med Health. 2002 January-March; 14(1): 9-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467202&dopt=Abstract

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Acute myelomonocytic leukemia preceded by secondary amenorrhea and presenting with central diabetes insipidus: a case report. Author(s): Yen CC, Tzeng CH, Liu JH, Chiou TJ, Hsieh RK, Wang WS, Chen PM. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1997 October; 60(4): 213-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9439051&dopt=Abstract

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Administration of L-thyroxine does not improve the response of the hypothalamopituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea. Author(s): De Leo V, la Marca A, Lanzetta D, Morgante G. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2000 May; 90(1): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10767520&dopt=Abstract

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Altered binding of serum thyroid hormone to thyroxine-binding globulin in women with functional hypothalamic amenorrhea. Author(s): Dominguez CE, Laughlin GA, Nelson JC, Yen SS. Source: Fertility and Sterility. 1997 December; 68(6): 992-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9418685&dopt=Abstract

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Amenorrhea and bone health in adolescents and young women. Author(s): Gordon CM, Nelson LM. Source: Current Opinion in Obstetrics & Gynecology. 2003 October; 15(5): 377-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501240&dopt=Abstract

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Amenorrhea associated with contraception-an international study on acceptability. Author(s): Glasier AF, Smith KB, van der Spuy ZM, Ho PC, Cheng L, Dada K, Wellings K, Baird DT. Source: Contraception. 2003 January; 67(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521650&dopt=Abstract

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Amenorrhea frequency with continuous combined hormone replacement therapy: a retrospective analysis. Menopause Study Group. Author(s): Pickar JH, Bottiglioni F, Archer DF. Source: Climacteric : the Journal of the International Menopause Society. 1998 June; 1(2): 130-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913408&dopt=Abstract

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Amenorrhea in adolescents. Sorting out the clinical picture. Author(s): Mauldon M. Source: Adv Nurse Pract. 2000 July; 8(7): 44-51; Quiz 52-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261038&dopt=Abstract

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Amenorrhea in beta-homozygous thalassemia major. Author(s): Tolis G, Papandreou A, Karydis I. Source: Annals of the New York Academy of Sciences. 1997 June 17; 816: 274-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238277&dopt=Abstract

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Amenorrhea in the athlete. Author(s): Gidwani GP. Source: Adolescent Medicine (Philadelphia, Pa.). 1999 June; 10(2): 275-90, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10370710&dopt=Abstract

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Amenorrhea induced by adjuvant chemotherapy in early breast cancer patients: prognostic role and clinical implications. Author(s): Del Mastro L, Venturini M, Sertoli MR, Rosso R. Source: Breast Cancer Research and Treatment. 1997 April; 43(2): 183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9131274&dopt=Abstract

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Amenorrhea-galactorrhea syndrome as an uncommon manifestation of isolated neurosarcoidosis. Author(s): Tamagno G, Murialdo G. Source: Ann Ital Med Int. 2001 October-December; 16(4): 260-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799635&dopt=Abstract

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Analyzing amenorrhea. Author(s): Morrison E. Source: Hosp Pract (Off Ed). 1998 July 15; 33(7): 89-100, 103; Discussion 103-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9679507&dopt=Abstract

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Anorexia, bulimia, and exercise-induced amenorrhea: medical approach. Author(s): Warren MP. Source: Curr Ther Endocrinol Metab. 1997; 6: 13-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9174690&dopt=Abstract

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Assessment of hypothalamic-pituitary function by hormonal pulsatility, gonadotropin-releasing hormone and thyrotropin-releasing hormone testing in women with euprolactinemic secondary amenorrhea. Author(s): Lin KC, Lee JN, Jong SB. Source: Kaohsiung J Med Sci. 1998 November; 14(11): 698-705. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9838765&dopt=Abstract

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Athletic amenorrhea. Author(s): Wolf AS, Marx K, Ulrich U. Source: Annals of the New York Academy of Sciences. 1997 June 17; 816: 295-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238280&dopt=Abstract

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Autonomic and neuroendocrine responses to stress in patients with functional hypothalamic secondary amenorrhea. Author(s): Gallinelli A, Matteo ML, Volpe A, Facchinetti F. Source: Fertility and Sterility. 2000 April; 73(4): 812-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10731545&dopt=Abstract

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Biliary atresia with hyperandrogenic amenorrhea. Author(s): Hebiguchi T, Kato T, Yoshino H, Mizuno M, Takahashi T, Fukuda J, Tanaka T. Source: Pediatric Surgery International. 2001 March; 17(2-3): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315291&dopt=Abstract

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Biliary atresia with hyperandrogenic amenorrhea: case report. Author(s): Hebiguchi T, Kato T, Yoshino H, Mizuno M, Takahashi T, Fukuda J, Tanaka T. Source: Pediatric Surgery International. 2000; 16(1-2): 113-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10663856&dopt=Abstract

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Body image in secondary amenorrhea. Author(s): Orlandi E, Guaraldi GP, Facchinetti F. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 1997 March; 18(1): 45-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9138206&dopt=Abstract

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Bone density and amenorrhea in ballet dancers are related to a decreased resting metabolic rate and lower leptin levels. Author(s): Kaufman BA, Warren MP, Dominguez JE, Wang J, Heymsfield SB, Pierson RN. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 June; 87(6): 2777-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050250&dopt=Abstract

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Bone mineral changes in young women with hypothalamic amenorrhea treated with oral contraceptives, medroxyprogesterone, or placebo over 12 months. Author(s): Hergenroeder AC, Smith EO, Shypailo R, Jones LA, Klish WJ, Ellis K. Source: American Journal of Obstetrics and Gynecology. 1997 May; 176(5): 1017-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9166162&dopt=Abstract

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Bone mineral density in primary and secondary amenorrhea. Author(s): Choktanasiri W, Rojanasakul A, Rajatanavin R. Source: J Med Assoc Thai. 2000 March; 83(3): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10808678&dopt=Abstract

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Bone mineral metabolism in diet-induced amenorrhea. Author(s): Bruni V, Bigozzi L, Dei M, Brandi ML. Source: Annals of the New York Academy of Sciences. 1997 June 17; 816: 250-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238275&dopt=Abstract

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Breastfeeding, amenorrhea and contraceptive practice among postpartum women in Zibo, China. Author(s): Zhang LY, Liu YR, Shah IH, Tian KW, Zhang LH. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 2002 September; 7(3): 121-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428929&dopt=Abstract

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Case report: Teenage girl with proteinuria and amenorrhea. Author(s): Hausladen J, Granahan E, Bockenhauer D. Source: Current Opinion in Pediatrics. 2001 April; 13(2): 150-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11317057&dopt=Abstract

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Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea. Author(s): Berga SL, Loucks-Daniels TL, Adler LJ, Chrousos GP, Cameron JL, Matthews KA, Marcus MD. Source: American Journal of Obstetrics and Gynecology. 2000 April; 182(4): 776-81; Discussion 781-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764453&dopt=Abstract

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Characterization of pulsatile secretion of gonadotropin and prolactin in women with normal menstrual cycle, secondary amenorrhea and polycystic ovary syndrome (PCOS). Author(s): Lin KC, Lee JN. Source: Kaohsiung J Med Sci. 1998 February; 14(2): 61-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9542361&dopt=Abstract

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Chemotherapy-induced amenorrhea and fertility in women undergoing adjuvant treatment for breast cancer. Author(s): Minton SE, Munster PN. Source: Cancer Control : Journal of the Moffitt Cancer Center. 2002 NovemberDecember; 9(6): 466-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514564&dopt=Abstract

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Classification of hypothalamic progestin-nonresponsive amenorrhea by secretion pattern of serum LH. Author(s): Kondoh Y, Uemura T, Minaguchi H. Source: Endocrine Journal. 1997 August; 44(4): 501-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9447282&dopt=Abstract

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Clinical manifestations of low bone mass in amenorrhea patients with elevated follicular stimulating hormone. Author(s): Yu Q, Lin S, He F, Li B, Lin Y, Zhang T, Zhang Y. Source: Chinese Medical Journal. 2002 September; 115(9): 1376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411116&dopt=Abstract

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Clinical pathologic correlation: Recurrent abdominal pain and primary amenorrhea. Author(s): Omar H. Source: Journal of Pediatric and Adolescent Gynecology. 2002 April; 15(2): 105-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057534&dopt=Abstract

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Clinical syndromes of primary amenorrhea. Author(s): Batrinos ML, Panitsa-Faflia C. Source: Annals of the New York Academy of Sciences. 1997 June 17; 816: 235-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238273&dopt=Abstract

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Clinical syndromes of secondary amenorrhea. Author(s): Mavroudis K. Source: Annals of the New York Academy of Sciences. 1997 June 17; 816: 241-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238274&dopt=Abstract

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Clinicopathologic exercise: hypoglycemia in a young woman with amenorrhea. Author(s): Greenberg LW, Badosa F, Niakosari A, Schneider A, Zaeri N, Schindler AM. Source: The Journal of Pediatrics. 2000 June; 136(6): 818-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839882&dopt=Abstract

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Comment on health issues for women athletes: exercise-induced amenorrhea. Author(s): De Cree C. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 December; 84(12): 4750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599754&dopt=Abstract

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Concomitant occurrence of macroprolactin, exercise-induced amenorrhea, and a pituitary lesion: a diagnostic pitfall. Case report. Author(s): Cattaneo FA, Fahie-Wilson MN. Source: Journal of Neurosurgery. 2001 August; 95(2): 334-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11780906&dopt=Abstract

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Contemporary issues in primary amenorrhea. Author(s): Timmreck LS, Reindollar RH. Source: Obstetrics and Gynecology Clinics of North America. 2003 June; 30(2): 287-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836721&dopt=Abstract

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Continuous hormone replacement therapy for menopause combining nomegestrol acetate and gel, patch, or oral estrogen: a comparison of amenorrhea rates. Author(s): Blanc B, Cravello L, Micheletti MC, d'Ercole C, Zartarian M. Source: Clinical Therapeutics. 1998 September-October; 20(5): 901-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829442&dopt=Abstract

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Contraceptive use and pregnancy before and after introducing lactational amenorrhea (LAM) in a postpartum program. Author(s): Hardy E, Santos LC, Osis MJ, Carvalho G, Cecatti JG, Faundes A. Source: Advances in Contraception : the Official Journal of the Society for the Advancement of Contraception. 1998 March; 14(1): 59-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9587009&dopt=Abstract

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Counseling female athletes: application of the stages of change model to avoid disordered eating, amenorrhea, and osteoporosis. Author(s): Bass M, Turner L, Hunt S. Source: Psychological Reports. 2001 June; 88(3 Pt 2): 1153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597070&dopt=Abstract

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C-peptide levels and the duration of lactational amenorrhea. Author(s): Ellison PT, Valeggia CR. Source: Fertility and Sterility. 2003 November; 80(5): 1279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607590&dopt=Abstract

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Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional intake. Author(s): Miller KK, Parulekar MS, Schoenfeld E, Anderson E, Hubbard J, Klibanski A, Grinspoon SK. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 July; 83(7): 2309-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9661600&dopt=Abstract

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Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies. Author(s): Meduri G, Touraine P, Beau I, Lahuna O, Desroches A, Vacher-Lavenu MC, Kuttenn F, Misrahi M. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3491-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915623&dopt=Abstract

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Delayed puberty in girls and primary amenorrhea. Author(s): Thomas MA, Rebar RW. Source: Curr Ther Endocrinol Metab. 1997; 6: 223-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9174742&dopt=Abstract

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Demonstration of reserved anterior pituitary function among patients with amenorrhea after postpartum hemorrhage. Author(s): Huang YY, Ting MK, Hsu BR, Tsai JS. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 April; 14(2): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10836196&dopt=Abstract

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Detection of a silent pituitary somatotroph adenoma in a patient with amenorrhea and/or galactorrhea: paradoxical response of GH in TRH or GnRH provocation test. Author(s): Matsuno A, Ogino Y, Itoh J, Osamura RY, Nagashima T. Source: Endocrine Journal. 2000 March; 47 Suppl: S105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890196&dopt=Abstract

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Diagnostic role of inhibin B in resistant ovary syndrome associated with secondary amenorrhea. Author(s): Arici A, Matalliotakis IM, Koumantakis GE, Goumenou AG, Neonaki MA, Koumantakis EE. Source: Fertility and Sterility. 2002 December; 78(6): 1324-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477534&dopt=Abstract

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Effectiveness of Cyclofem in the treatment of depot medroxyprogesterone acetate induced amenorrhea. Author(s): Piya-Anant M, Koetsawang S, Patrasupapong N, Dinchuen P, d'Arcangues C, Piaggio G, Pinol A. Source: Contraception. 1998 January; 57(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554247&dopt=Abstract

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Effectiveness of switching to quetiapine for neuroleptic-induced amenorrhea. Author(s): Takahashi H, Higuchi H, Kamata M, Naitoh S, Yoshida K, Shimizu T, Sugita T. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Summer; 15(3): 375-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928517&dopt=Abstract

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Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea. Author(s): Grinspoon SK, Friedman AJ, Miller KK, Lippman J, Olson WH, Warren MP. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3651-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915650&dopt=Abstract

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Effects of age at introduction of complementary foods to breast-fed infants on duration of lactational amenorrhea in Honduran women. Author(s): Dewey KG, Cohen RJ, Rivera LL, Canahuati J, Brown KH. Source: The American Journal of Clinical Nutrition. 1997 May; 65(5): 1403-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9129469&dopt=Abstract

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Effects of cyproheptadine clorhydrate, a serotonin receptor antagonist, on endocrine parameters in weight-loss related amenorrhea. Author(s): Genazzani AD, Strucchi C, Malavasi B, Tortolani F, Vecchi F, Luisi S, Petraglia F. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2001 August; 15(4): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560101&dopt=Abstract

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Effects of ovariectomy on intramuscular energy metabolism in young rats: how does sports-related-amenorrhea affect muscles of young female athletes? Author(s): Sasa T, Sairyo K, Yoshida N, Ishikawa M, Fukunaga M. Source: Journal of Physiological Anthropology and Applied Human Science. 2001 March; 20(2): 125-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385935&dopt=Abstract

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Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone deficiency in women with hypothalamic amenorrhea. Author(s): Kadva A, Djahanbakhch O, Monson J, Di WL, Silman R. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 October; 83(10): 3653-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9768680&dopt=Abstract

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Endocrine causes of amenorrhea. Author(s): Fogel CI. Source: Lippincott's Primary Care Practice. 1997 November-December; 1(5): 507-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384139&dopt=Abstract

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Endocrinology teaching rounds: primary amenorrhea in a 17-year-old woman. Author(s): Olson BR. Source: Journal of Women's Health & Gender-Based Medicine. 2000 June; 9(5): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10883940&dopt=Abstract

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Estrogen replacement therapy modulates spontaneous GH secretion but does not affect GH-RH-induced GH response and low T3 syndrome in women with hypothalamic amenorrhea associated to weight-loss. Author(s): Genazzani AD, Gamba O, Petraglia F. Source: J Endocrinol Invest. 1998 June; 21(6): 353-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9699126&dopt=Abstract

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Evaluation and management of amenorrhea. Author(s): McIver B, Romanski SA, Nippoldt TB. Source: Mayo Clinic Proceedings. 1997 December; 72(12): 1161-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9413300&dopt=Abstract

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Factors underlying changes in bone mineral during postpartum amenorrhea and lactation. Author(s): Holmberg-Marttila D, Sievanen H, Laippala P, Tuimala R. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2000; 11(7): 570-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069190&dopt=Abstract

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Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. Author(s): Warren MP, Voussoughian F, Geer EB, Hyle EP, Adberg CL, Ramos RH. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 March; 84(3): 873-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084564&dopt=Abstract

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Gonadotropin-releasing hormone for infertility in women with primary hypothalamic amenorrhea. Toward a more-interventional approach. Author(s): Kesrouani A, Abdallah MA, Attieh E, Abboud J, Atallah D, Makhoul C. Source: J Reprod Med. 2001 January; 46(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11209627&dopt=Abstract

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Gynecology case challenge--persistent amenorrhea postpartum. Author(s): Hill DA. Source: Medscape Women's Health [electronic Resource]. 1998 May; 3(3): 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9732094&dopt=Abstract

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Health issues for women athletes: exercise-induced amenorrhea. Author(s): Warren MP. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 June; 84(6): 1892-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372682&dopt=Abstract

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Herbal medicine (Shakuyaku-kanzo-to) in the treatment of risperidone-induced amenorrhea. Author(s): Yamada K, Kanba S, Yagi G, Asai M. Source: Journal of Clinical Psychopharmacology. 1999 August; 19(4): 380-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440470&dopt=Abstract

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Hormone replacement in the adolescent with anorexia and hypothalamic amenorrhea-yes or no? Author(s): Jamieson MA. Source: Journal of Pediatric and Adolescent Gynecology. 2001 February; 14(1): 39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358707&dopt=Abstract

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How reliably does 12-month amenorrhea define final menstrual period? Data from a longitudinal study. Author(s): Guthrie J, Dennerstein L, Burger H. Source: Climacteric : the Journal of the International Menopause Society. 2002 March; 5(1): 92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974565&dopt=Abstract

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Hyperandrogenicity is an alternative mechanism underlying oligomenorrhea or amenorrhea in female athletes and may improve physical performance. Author(s): Rickenlund A, Carlstrom K, Ekblom B, Brismar TB, von Schoultz B, Hirschberg AL. Source: Fertility and Sterility. 2003 April; 79(4): 947-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749436&dopt=Abstract

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Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. Author(s): Laughlin GA, Yen SS. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 January; 82(1): 31821. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8989281&dopt=Abstract

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Hypothalamic amenorrhea and cardiovascular hormones: changes of plasma calcitonin gene-related peptide and atrial natriuretic peptide levels. Author(s): Bernardi F, Valentini A, Margutti A, Santuz M, Degli Uberti EC, Petraglia F, Genazzani AR. Source: J Endocrinol Invest. 1998 April; 21(4): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624600&dopt=Abstract

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Hypothalamic amenorrhea and hidden nutritional insults. Author(s): Warren MP, Holderness CC, Lesobre V, Tzen R, Vossoughian F, BrooksGunn J. Source: Journal of the Society for Gynecologic Investigation. 1994 January-March; 1(1): 84-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9419753&dopt=Abstract

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Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test. Author(s): Meczekalski B, Tonetti A, Monteleone P, Bernardi F, Luisi S, Stomati M, Luisi M, Petraglia F, Genazzani AR. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2000 March; 142(3): 280-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10700723&dopt=Abstract

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Hypothalamic amenorrhea. The effects of environmental stresses on the reproductive system: a central effect of the central nervous system. Author(s): Warren MP, Fried JL. Source: Endocrinology and Metabolism Clinics of North America. 2001 September; 30(3): 611-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571933&dopt=Abstract

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Identification of allelic variants in the follicle-stimulating hormone receptor genes of females with or without hypergonadotropic amenorrhea. Author(s): Liu JY, Gromoll J, Cedars MI, La Barbera AR. Source: Fertility and Sterility. 1998 August; 70(2): 326-31. Erratum In: Fertil Steril 1998 June; 71(6): 1174. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9696229&dopt=Abstract

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Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea. Author(s): Genazzani AD, Bersi C, Luisi S, Fruzzetti F, Malavasi B, Luisi M, Petraglia F, Genazzani AR. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 September; 78(3): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595505&dopt=Abstract

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Increased serum level of inhibin causes amenorrhea in a granulosa cell tumor patient. Author(s): Sakamoto S, Sakamoto M, Nagai A, Obayashi S, Kubota T, Aso T. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1998 February; 77(2): 243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9512338&dopt=Abstract

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Inducing amenorrhea during bone marrow transplantation. A pilot study of leuprolide acetate. Author(s): Laufer MR, Townsend NL, Parsons KE, Brody KA, Diller LR, Emans SJ, Guinan EC. Source: J Reprod Med. 1997 September; 42(9): 537-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9336747&dopt=Abstract

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Induction of ovulation with clomiphene citrate in combination with metoclopramide in patients with amenorrhea of hypothalamic origin. Author(s): Mendes MC, Ferriani RA, Sala MM, Moura MD, de Sa MF. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1999 June; 13(3): 149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10451805&dopt=Abstract

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Infant feeding and lactational amenorrhea in Sagamu, Nigeria. Author(s): Dada OA, Akesode FA, Olanrewaju DM, Olowu OA, Sule-Odu O, Fakoya TA, Oluwole FA, Odunlami BV; World Health Organization Task Force on Methods for the Natural Regulation of Fertility. Source: Afr J Reprod Health. 2002 August; 6(2): 39-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484341&dopt=Abstract

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Intervillous and spiral artery flows in normal pregnancies between 5 and 10 weeks of amenorrhea using color Doppler ultrasonography. Author(s): Alouini S, Carbillon L, Perrot N, Uzan S, Uzan M. Source: Fetal Diagnosis and Therapy. 2002 May-June; 17(3): 163-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914569&dopt=Abstract

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Is amenorrhea a critical criterion for anorexia nervosa? Author(s): Cachelin FM, Maher BA. Source: Journal of Psychosomatic Research. 1998 March-April; 44(3-4): 435-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9587885&dopt=Abstract

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Is there an association between athletic amenorrhea and endothelial cell dysfunction? Author(s): Zeni Hoch A, Dempsey RL, Carrera GF, Wilson CR, Chen EH, Barnabei VM, Sandford PR, Ryan TA, Gutterman DD. Source: Medicine and Science in Sports and Exercise. 2003 March; 35(3): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618566&dopt=Abstract

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Lactational amenorrhea is associated with child age at the time of introduction of complementary food: a prospective cohort study in rural Senegal, West Africa. Author(s): Simondon KB, Delaunay V, Diallo A, Elguero E, Simondon F. Source: The American Journal of Clinical Nutrition. 2003 July; 78(1): 154-61. Erratum In: Am J Clin Nutr. 2003 November; 78(5): 1047. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816785&dopt=Abstract

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Lactational amenorrhea/anovulation and some of their determinants: a comparison of well-nourished and undernourished women. Author(s): Wasalathanthri S, Tennekoon KH. Source: Fertility and Sterility. 2001 August; 76(2): 317-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476779&dopt=Abstract

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Leptin in anorexia nervosa and amenorrhea. Author(s): Licinio J. Source: Molecular Psychiatry. 1997 July; 2(4): 267-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9246658&dopt=Abstract

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Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors. Author(s): Falsetti L, Gambera A, Barbetti L, Specchia C. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 February; 87(2): 500-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836275&dopt=Abstract

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Low dose flutamide in the treatment of acne vulgaris in women with or without oligomenorrhea or amenorrhea. Author(s): Wang HS, Wang TH, Soong YK. Source: Changgeng Yi Xue Za Zhi. 1999 September; 22(3): 423-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584414&dopt=Abstract

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Low leptin levels predict amenorrhea in underweight and eating disordered females. Author(s): Kopp W, Blum WF, von Prittwitz S, Ziegler A, Lubbert H, Emons G, Herzog W, Herpertz S, Deter HC, Remschmidt H, Hebebrand J. Source: Molecular Psychiatry. 1997 July; 2(4): 335-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9246675&dopt=Abstract

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Low levels of serum inhibin A and inhibin B in women with hypergonadotropic amenorrhea and evidence of high levels of activin A in women with hypothalamic amenorrhea. Author(s): Petraglia F, Hartmann B, Luisi S, Florio P, Kirchengast S, Santuz M, Genazzani AD, Genazzani AR. Source: Fertility and Sterility. 1998 November; 70(5): 907-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806574&dopt=Abstract

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Low-dose human chorionic gonadotropin therapy can improve sensitivity to exogenous follicle-stimulating hormone in patients with secondary amenorrhea. Author(s): Filicori M, Cognigni GE, Taraborrelli S, Spettoli D, Ciampaglia W, de Fatis CT. Source: Fertility and Sterility. 1999 December; 72(6): 1118-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10593393&dopt=Abstract

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Management quandary. Primary amenorrhea due to mixed gonadal dysgenesis. Author(s): Breech L, Merritt D. Source: Journal of Pediatric and Adolescent Gynecology. 1998 November; 11(4): 195-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806133&dopt=Abstract

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Maternal nutritional status is inversely associated with lactational amenorrhea in Sub-Saharan Africa: results from demographic and health surveys II and III. Author(s): Peng YK, Hight-Laukaran V, Peterson AE, Perez-Escamilla R. Source: The Journal of Nutrition. 1998 October; 128(10): 1672-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9772135&dopt=Abstract

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Maxillary ossification in a series of six human embryos and fetuses aged from 9 to 12 weeks of amenorrhea: clinical implications. Author(s): Vacher C, Copin H, Sakka M. Source: Surgical and Radiologic Anatomy : Sra. 1999; 21(4): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10549083&dopt=Abstract

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Meeting the needs of young women with secondary amenorrhea and spontaneous premature ovarian failure. Author(s): Alzubaidi NH, Chapin HL, Vanderhoof VH, Calis KA, Nelson LM. Source: Obstetrics and Gynecology. 2002 May; 99(5 Pt 1): 720-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978278&dopt=Abstract

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Menstrual disorders. Amenorrhea. Author(s): Pletcher JR, Slap GB. Source: Pediatric Clinics of North America. 1999 June; 46(3): 505-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10384804&dopt=Abstract

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Menstrual nirvana: amenorrhea through the use of continuous oral contraceptives. Author(s): Edelman A. Source: Curr Womens Health Rep. 2002 December; 2(6): 434-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429077&dopt=Abstract

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Molecular breakpoint analysis and relevance of variable mosaicism in a woman with short stature, primary amenorrhea, unilateral gonadoblastoma, and a 46,X,del(Y)(q11)/45,X karyotype. Author(s): Kotzot D, Dufke A, Tzschach A, Baeckert-Sifeddine IT, Geppert M, Holland H, Florus JM, Froster UG. Source: American Journal of Medical Genetics. 2002 September 15; 112(1): 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239720&dopt=Abstract

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Multicenter study of the lactational amenorrhea method (LAM) III: effectiveness, duration, and satisfaction with reduced client-provider contact. Author(s): Peterson AE, Perez-Escamilla R, Labboka MH, Hight V, von Hertzen H, Van Look P. Source: Contraception. 2000 November; 62(5): 221-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172792&dopt=Abstract

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Multicenter study of the Lactational Amenorrhea Method (LAM): I. Efficacy, duration, and implications for clinical application. Author(s): Labbok MH, Hight-Laukaran V, Peterson AE, Fletcher V, von Hertzen H, Van Look PF. Source: Contraception. 1997 June; 55(6): 327-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9262927&dopt=Abstract

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Multicenter study of the Lactational Amenorrhea Method (LAM): II. Acceptability, utility, and policy implications. Author(s): Hight-Laukaran V, Labbok MH, Peterson AE, Fletcher V, von Hertzen H, Van Look PF. Source: Contraception. 1997 June; 55(6): 337-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9262928&dopt=Abstract

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Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation. Author(s): Perkins RB, Hall JE, Martin KA. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 June; 84(6): 1905-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372685&dopt=Abstract

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Nonfunctioning pituitary macroadenoma presenting with mild hyperprolactinemia and amenorrhea. Author(s): Hansen KA, Tho SP, Gomez F, McDonough PG. Source: Fertility and Sterility. 1999 October; 72(4): 663-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10521106&dopt=Abstract

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Nurse-midwives' knowledge and promotion of lactational amenorrhea and other natural family-planning methods for child spacing. Author(s): Fehring RJ, Hanson L, Stanford JB. Source: Journal of Midwifery & Women's Health. 2001 March-April; 46(2): 68-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370692&dopt=Abstract

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Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. Author(s): Laughlin GA, Dominguez CE, Yen SS. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 January; 83(1): 2532. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9435412&dopt=Abstract

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Occurrence of osteopenia among adolescent girls with oligo/amenorrhea. Author(s): Csermely T, Halvax L, Schmidt E, Zambo K, Vadon G, Szabo I, Szilagyi A. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 April; 16(2): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12012630&dopt=Abstract

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Oral glucose challenge effects on growth and sex steroid hormones in normal women and women with hypothalamic amenorrhea. Author(s): Takeuchi T, Kawana T. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1998 May; 61(2): 171-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639222&dopt=Abstract

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Osteopenia in exercise-associated amenorrhea using ballet dancers as a model: a longitudinal study. Author(s): Warren MP, Brooks-Gunn J, Fox RP, Holderness CC, Hyle EP, Hamilton WG. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 July; 87(7): 3162-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107218&dopt=Abstract

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Ovarian resistance to luteinizing hormone: a novel cause of amenorrhea and infertility. Author(s): Arnhold IJ, Latronico AC, Batista MC, Carvalho FM, Chrousos GP, Mendonca BB. Source: Fertility and Sterility. 1997 February; 67(2): 394-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9022621&dopt=Abstract

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Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus. Author(s): Georgopoulos NA, Markou KB, Pappas AP, Protonatariou A, Vagenakis GA, Sykiotis GP, Dimopoulos PA, Tzingounis VA. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2001 December; 15(6): 421-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11826765&dopt=Abstract

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Pediatric management problems. Amenorrhea. Author(s): Smith D. Source: Pediatric Nursing. 2001 January-February; 27(1): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025139&dopt=Abstract

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Permanent amenorrhea associated with endometrial atrophy after uterine artery embolization for symptomatic uterine fibroids. Author(s): Tropeano G, Litwicka K, Di Stasi C, Romano D, Mancuso S. Source: Fertility and Sterility. 2003 January; 79(1): 132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524076&dopt=Abstract

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Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study. Author(s): Warren MP, Brooks-Gunn J, Fox RP, Holderness CC, Hyle EP, Hamilton WG, Hamilton L. Source: Fertility and Sterility. 2003 August; 80(2): 398-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909505&dopt=Abstract

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Pharmacologic management of athletic amenorrhea. Author(s): Fagan KM. Source: Clinics in Sports Medicine. 1998 April; 17(2): 327-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9580845&dopt=Abstract

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Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea. Author(s): Genazzani AD, Stomati M, Bersi C, Luisi S, Fedalti M, Santuz M, Esposito G, Petraglia F, Genazzani AR. Source: J Endocrinol Invest. 2000 September; 23(8): 526-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11021769&dopt=Abstract

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Policy considerations for the introduction and promotion of the lactational amenorrhea method: advantages and disadvantages of LAM. Author(s): Kennedy KI, Kotelchuck M. Source: Journal of Human Lactation : Official Journal of International Lactation Consultant Association. 1998 September; 14(3): 191-203. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10205427&dopt=Abstract

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Possible involvement of hypersecretion of progesterone from an adrenal adenoma without androgen excess in primary amenorrhea. Author(s): Nishikawa T. Source: Intern Med. 2002 November; 41(11): 912. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487155&dopt=Abstract

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Postpartum contraception: the lactational amenorrhea method. Author(s): Vekemans M. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 1997 June; 2(2): 105-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9678098&dopt=Abstract

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Predictors of sustained amenorrhea from pulsed intravenous cyclophosphamide in premenopausal women with systemic lupus erythematosus. Author(s): Ioannidis JP, Katsifis GE, Tzioufas AG, Moutsopoulos HM. Source: The Journal of Rheumatology. 2002 October; 29(10): 2129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375322&dopt=Abstract

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Prevalence of bone mineral changes during postpartum amenorrhea and after resumption of menstruation. Author(s): Holmberg-Marttila D, Sievanen H. Source: American Journal of Obstetrics and Gynecology. 1999 March; 180(3 Pt 1): 537-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10076124&dopt=Abstract

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Primary amenorrhea accompanied by adrenal adenoma: start of menarche soon after tumor resection. Author(s): Takahashi Y, Ninomiya J, Horiguchi J, Shimizu H, Sato M, Koibuchi Y, Yoshida T, Yoshida M, Takata D, Odawara H, Yokoe T, Iino Y, Morishita Y, Mori M. Source: Intern Med. 2002 November; 41(11): 972-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487170&dopt=Abstract

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Primary amenorrhea caused by crushing trauma of the pelvis. Author(s): Donner GG, Pel M, Lammes FB. Source: American Journal of Obstetrics and Gynecology. 2000 August; 183(2): 500-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942496&dopt=Abstract

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Primary amenorrhea with Xq duplication. Author(s): Rajangam S, Lincoln S, Tilak P, Thomas IM. Source: Indian Journal of Medical Sciences. 1999 February; 53(2): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798023&dopt=Abstract

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Primary amenorrhea: evaluation with MR imaging. Author(s): Reinhold C, Hricak H, Forstner R, Ascher SM, Bret PM, Meyer WR, Semelka RC. Source: Radiology. 1997 May; 203(2): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9114092&dopt=Abstract

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Progestogens in the treatment of secondary amenorrhea. Author(s): Simon JA. Source: J Reprod Med. 1999 February; 44(2 Suppl): 185-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392030&dopt=Abstract

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Prolactinoma causing secondary amenorrhea in a woman with Ullrich-Turner syndrome. Author(s): Dotsch J, Schoof E, Hensen J, Dorr HG. Source: Hormone Research. 1999; 51(5): 256-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559672&dopt=Abstract

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Psychological correlates of functional hypothalamic amenorrhea. Author(s): Marcus MD, Loucks TL, Berga SL. Source: Fertility and Sterility. 2001 August; 76(2): 310-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476778&dopt=Abstract

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Psychoneuroendocrine correlates of secondary amenorrhea. Author(s): Nappi RE, Facchinetti F. Source: Archives of Women's Mental Health. 2003 April; 6(2): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720058&dopt=Abstract

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Rachitic rosary in a well chelated thalassaemic patient with primary amenorrhea (patient report). Author(s): Lauriola AL, Tangerini A, Lodi A, Gamberini MR, Testa MR, Orzincolo C, De Sanctis V, Vullo C. Source: J Pediatr Endocrinol Metab. 1998; 11 Suppl 3: 979-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10091177&dopt=Abstract

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Recommendations for exogenous estrogen to prevent glucocorticoid-induced osteoporosis in premenopausal women with oligo- or amenorrhea: comment on the American College of Rheumatology recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Author(s): Buyon JP, Dooley MA, Meyer WR, Petri M, Licciardi F. Source: Arthritis and Rheumatism. 1997 August; 40(8): 1548-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9259444&dopt=Abstract

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Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy. Author(s): Berga SL, Marcus MD, Loucks TL, Hlastala S, Ringham R, Krohn MA. Source: Fertility and Sterility. 2003 October; 80(4): 976-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556820&dopt=Abstract

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Results of cytogenetic investigation in adolescent patients with primary or secondary amenorrhea. Author(s): Temocin K, Vardar MA, Suleymanova D, Ozer E, Tanriverdi N, Demirhan O, Kadayifci O. Source: Journal of Pediatric and Adolescent Gynecology. 1997 May; 10(2): 86-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9179808&dopt=Abstract

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Resumption of menstruation after amenorrhea in women treated by endometrial ablation and myometrial resection. Author(s): Seeras RC, Gilliland GB. Source: The Journal of the American Association of Gynecologic Laparoscopists. 1997 May; 4(3): 305-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9154778&dopt=Abstract

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Risperidone and associated amenorrhea: a report of 5 cases. Author(s): Kim YK, Kim L, Lee MS. Source: The Journal of Clinical Psychiatry. 1999 May; 60(5): 315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10362440&dopt=Abstract

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Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women. Author(s): Weisinger JR, Gonzalez L, Alvarez H, Hernandez E, Carlini RG, Capriles F, Cervino M, Martinis R, Paz-Martinez V, Bellorin-Font E. Source: Kidney International. 2000 July; 58(1): 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10886579&dopt=Abstract

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Secondary amenorrhea and infertility caused by an inhibin-B-producing ovarian fibrothecoma. Author(s): Meyer AC, Papadimitriou JC, Silverberg SG, Sharara FI. Source: Fertility and Sterility. 2000 February; 73(2): 258-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10685524&dopt=Abstract

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Secondary amenorrhea caused by hydrocephalus due to aqueductal stenosis : report of two cases. Author(s): Lee JK, Kim JH, Kim JS, Kim TS, Jung S, Kim SH, Kang SS, Lee JH. Source: Journal of Korean Medical Science. 2001 August; 16(4): 532-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511805&dopt=Abstract

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Secondary amenorrhea leading to osteoporosis: incidence and prevention. Author(s): McGee C. Source: The Nurse Practitioner. 1997 May; 22(5): 38, 41-5, 48 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172234&dopt=Abstract

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Secondary amenorrhea with severe intrauterine adhesions and chronic uterine torsion after Cesarean section in a teenage girl. Author(s): Badawy SZ, Orbuch L, Khurana KK. Source: Journal of Pediatric and Adolescent Gynecology. 1998 May; 11(2): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9593609&dopt=Abstract

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Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea. Author(s): Grinspoon S, Miller K, Coyle C, Krempin J, Armstrong C, Pitts S, Herzog D, Klibanski A. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 June; 84(6): 2049-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372709&dopt=Abstract

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Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients. Author(s): Scillitani A, Chiodini I, Carnevale V, Giannatempo GM, Frusciante V, Villella M, Pileri M, Guglielmi G, Di Giorgio A, Modoni S, Fusilli S, Di Cerbo A, Liuzzi A. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1997 October; 12(10): 1729-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9333135&dopt=Abstract

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Spontaneous pregnancy after 13 years of amenorrhea in a patient with a voluminous ovarian dysgerminoma and submitted to left adnexectomy and radiotherapy. Author(s): Garcea N, Campo S, Marone M, Garcea R. Source: Gynecologic and Obstetric Investigation. 1998; 46(3): 214-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9736808&dopt=Abstract

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Successful pregnancy in a case of pituitary dwarfism complicated by diabetes insipidus and primary amenorrhea. Author(s): Narahara H, Kawano Y, Yoshimatsu J, Miyakawa I. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 August; 79(8): 714-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10949242&dopt=Abstract

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Thalidomide induces amenorrhea in patients with lupus disease. Author(s): Ordi J, Cortes F, Martinez N, Mauri M, De Torres I, Vilardell M. Source: Arthritis and Rheumatism. 1998 December; 41(12): 2273-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9870886&dopt=Abstract

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The efficacy of hormone assays in the differential diagnosis of amenorrhea and menopause. Author(s): Chiecchio A, Malvano R, Vignati G. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2000 October; 38(10): 971-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11140631&dopt=Abstract

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The efficacy of the lactational amenorrhea method (LAM) among working women. Author(s): Valdes V, Labbok MH, Pugin E, Perez A. Source: Contraception. 2000 November; 62(5): 217-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172791&dopt=Abstract

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The female athlete triad: disordered eating, amenorrhea, and osteoporosis. Author(s): Anderson JM. Source: Conn Med. 1999 November; 63(11): 647-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589144&dopt=Abstract

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Therapeutic amenorrhea. Author(s): Hillard PJ. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 September-October; 21(5): 350-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10524445&dopt=Abstract

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Transient secondary amenorrhea in women treated by thalidomide. Author(s): Frances C, El Khoury S, Gompel A, Becherel PA, Chosidow O, Piette JC. Source: European Journal of Dermatology : Ejd. 2002 January-February; 12(1): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809598&dopt=Abstract

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Treatment of functional hypothalamic amenorrhea with hypnotherapy. Author(s): Tschugguel W, Berga SL. Source: Fertility and Sterility. 2003 October; 80(4): 982-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556821&dopt=Abstract

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Treatment of reduced bone mineral density in athletic amenorrhea: a pilot study. Author(s): Gibson JH, Mitchell A, Reeve J, Harries MG. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 10(4): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10692976&dopt=Abstract

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Understanding the female athlete triad: eating disorders, amenorrhea, and osteoporosis. Author(s): Beals KA, Brey RA, Gonyou JB. Source: The Journal of School Health. 1999 October; 69(8): 337-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10544368&dopt=Abstract

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Unexpected pregnancy during hormone-replacement therapy in a woman with elevated follicle-stimulating hormone levels and amenorrhea. Author(s): Laml T, Huber JC, Albrecht AE, Sintenis WA, Hartmann BW. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1999 April; 13(2): 89-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399052&dopt=Abstract

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Unraveling the mystery of chronic amenorrhea. Author(s): Seibert DC. Source: Lippincott's Primary Care Practice. 1998 May-June; 2(3): 319-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9644450&dopt=Abstract

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Use of the copper intrauterine device in the management of secondary amenorrhea. Author(s): Vesce F, Jorizzo G, Bianciotto A, Gotti G. Source: Fertility and Sterility. 2000 January; 73(1): 162-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10632433&dopt=Abstract

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Users' understanding of the lactational amenorrhea method and the occurrence of pregnancy. Author(s): Kennedy KI, Kotelchuck M, Visness CM, Kazi A, Ramos R. Source: Journal of Human Lactation : Official Journal of International Lactation Consultant Association. 1998 September; 14(3): 209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10205433&dopt=Abstract

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Variation in endometrial thickening in women with amenorrhea on tamoxifen. Author(s): Chang J, Powles TJ, Ashley SE, Iveson T, Gregory RK, Dowsett M. Source: Breast Cancer Research and Treatment. 1998 March; 48(1): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9541192&dopt=Abstract

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Virilizing adrenal adenoma and primary amenorrhea in a girl with adrenal hyperplasia. Author(s): Forsbach G, Guitron-Cantu A, Vazquez-Lara J, Mota-Morales M, DiazMendoza ML. Source: Archives of Gynecology and Obstetrics. 2000 February; 263(3): 134-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763843&dopt=Abstract

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Wilson disease manifested primarily as amenorrhea and accompanying thrombocytopenia. Author(s): Erkan T, Aktuglu C, Gulcan EM, Kutlu T, Cullu F, Apak H, Tumay GT. Source: The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. 2002 October; 31(4): 378-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359384&dopt=Abstract

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Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations. Author(s): Berga SL, Daniels TL, Giles DE. Source: Fertility and Sterility. 1997 June; 67(6): 1024-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9176439&dopt=Abstract

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

Finding Nutrition Studies on Amenorrhea 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.4 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 “amenorrhea” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

4 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.

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

A review of the female athlete triad (amenorrhea, osteoporosis and disordered eating). Author(s): Schneider Children's Hospital, Division of Adolescent Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, USA. [email protected] Source: Golden, N H Int-J-Adolesc-Med-Health. 2002 Jan-March; 14(1): 9-17 0334-0139

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Amenorrhea frequency with continuous combined hormone replacement therapy: a retrospective analysis. Menopause Study Group. Author(s): Wyeth-Ayerst Research, PO Box 8299, Philadelphia, PA 19101, USA. Source: Pickar, J H Bottiglioni, F Archer, D F Climacteric. 1998 June; 1(2): 130-6 1369-7137

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Amenorrhea. Source: Castiglia, P T J-Pediatr-Health-Care. 1996 Sep-October; 10(5): 226-7 0891-5245

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Analyzing amenorrhea. Author(s): University of California, Irvine, College of Medicine, USA. Source: Morrison, E Hosp-Pract-(Off-Ed). 1998 July 15; 33(7): 89-100, 103; discussion 1034 8750-2836

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Anorexia nervosa, athletics, and amenorrhea. Author(s): Division of Adolescent and Young Adult Medicine, Children's Hospital, Boston, Massachusetts. Source: Mansfield, M J Emans, S J Pediatr-Clin-North-Am. 1989 June; 36(3): 533-49 00313955

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Anorexia, bulimia, and exercise-induced amenorrhea: multidisciplinary approach. Author(s): Department of Psychonomics, Academisch Ziekenhuis Utrecht, The Netherlands. Source: Tuiten, A Jansen, A Koppeschaar, H P Curr-Ther-Endocrinol-Metab. 1994; 512-5 0831-652X

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Bigeminal pregnancy following oocytes donation to primitive amenorrheal woman (a woman with deletion of long arm of X chromosome). Author(s): 1. Department of Obstetrics and Gynecology, University of Catania. Source: Nardo, F Montoneri, C Bellanca, S Acta-Eur-Fertil. 1991 Sep-October; 22(5): 291-2 0587-2421

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Bilateral femoral neck stress fractures in an amenorrheic athlete. Author(s): Department of Orthopaedics, Brown University Medical School, Providence, Rhode Island, USA. Source: Voss, L DaSilva, M Trafton, P G Am-J-Orthopage 1997 November; 26(11): 789-92 1078-4519

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Bone health in adolescence: Anorexia and athletic amenorrhea. Source: Matkovic, V. Nutr-Today. Baltimore, Md. : Williams & Wilkins. April 1991. volume 26 (2) page 25-29. 0029-666X

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Breast feeding and post-partum amenorrhea in Serere women in Senegal. Author(s): Centre National de la Recherche Scientifique, Paris, France. Source: Rosetta, L Ann-Hum-Biol. 1989 Jul-August; 16(4): 311-20 0301-4460

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Delayed puberty and primary amenorrhea in girls. Author(s): University of Cincinnati College of Medicine, Ohio. Source: Thomas, M A Rebar, R W Curr-Ther-Endocrinol-Metab. 1994; 5195-7 0831-652X

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Delayed puberty in girls and primary amenorrhea. Author(s): University of Cincinnati College of Medicine, Ohio, USA. Source: Thomas, M A Rebar, R W Curr-Ther-Endocrinol-Metab. 1997; 6223-6 0831-652X

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Disparate effects of naloxone in hypothalamic amenorrhoea of athletes. Author(s): Department of Obstetrics and Gynecology, University Medical School, Szeged, Hungary. Source: Szabo, E Annus, J Zalanyi, S Falkay, G Funct-Neurol. 1987 Jul-September; 2(3): 315-21 0393-5264

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Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women. Author(s): Istituto Clinica Ostetrica e Ginecologica, University of Modena, Italy. Source: Botticelli, G Bacchi Modena, A Bresciani, D Villa, P Aguzzoli, L Florio, P Nappi, R E Petraglia, F Genazzani, A R J-Endocrinol-Invest. 1992 December; 15(11): 839-47 03914097

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Endothelin plasma levels in primary amenorrheic adolescents before and after estrogen treatment. Author(s): First Department of Obstetrics and Gynecology, Alexandra Hospital, University of Athens, Greece. Source: Creatsas, G C Malamitsi Puchner, A B Hassan, E A Economou, E B Aravantinos, D I J-Soc-Gynecol-Investig. 1996 Nov-December; 3(6): 350-3 1071-5576

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Estrogen replacement therapy modulates spontaneous GH secretion but does not affect GH-RH-induced GH response and low T3 syndrome in women with hypothalamic amenorrhea associated to weight-loss. Author(s): Clinica Ostetrica Ginecologica, University of Modena, Italy. Source: Genazzani, A D Gamba, O Petraglia, F J-Endocrinol-Invest. 1998 June; 21(6): 3537 0391-4097

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GNRH therapy in hypothalamic primary amenorrhea. Author(s): Department of Gynecology and Obstetrics, Universita Cattolica del Sacro Cuore, Roma, Italy. Source: Garcea, N Campo, S Dargenio, R Muscatello, R Dell'Elce, C Acta-Eur-Fertil. 1988 May-June; 19(3): 149-53 0587-2421

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Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea. Author(s): Department of Exercise & Sport Science, Oregon State University, Corvallis, USA. Source: Robinson, T L Snow Harter, C Taaffe, D R Gillis, D Shaw, J Marcus, R J-BoneMiner-Res. 1995 January; 10(1): 26-35 0884-0431

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Hypergonadotropic forms of amenorrhea in young women. Author(s): Department of Obstetrics and Gynecology, University of Cincinnati Medical Center, Ohio. Source: Rebar, R W Cedars, M I Endocrinol-Metab-Clin-North-Am. 1992 March; 21(1): 173-91 0889-8529

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Hypothalamic-pituitary-gonadal function in insulin treated diabetic women with and without amenorrhea. Source: Djursing, H Dan-Med-Bull. 1987 June; 34(3): 139-47 0907-8916

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Induction of ovulation in normo-androgenic women, affected by primary hypothalamic amenorrhea, with chronic pulsatile administration of GnRH, using an automatic portable pump (Zyklomat). Source: Amodeo, G Palermo, R Gabrielli, M Girasolo, A Acta-Eur-Fertil. 1987 Mar-April; 18(2): 113-5 0587-2421

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Lactation, nutrition, and postpartum amenorrhea in lowland Papua New Guinea. Author(s): Department of Anthropology, University of Washington, Seattle, WA 98195, USA. Source: Tracer, D P Hum-Biol. 1996 April; 68(2): 277-92 0018-7143

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Long-term follow-up of women with amenorrhea-galactorrhea treated with bromocriptine. Author(s): 2nd Department of Obstetrics and Gynecology, University of Bari, Italy. Source: Tartagni, M Nicastri, P L Diaferia, A Di Gesu, I Loizzi, P Clin-Exp-ObstetGynecol. 1995; 22(4): 301-6 0390-6663

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Low dose flutamide in the treatment of acne vulgaris in women with or without oligomenorrhea or amenorrhea. Author(s): Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital, Taipei, Taiwan, R.O.C. Source: Wang, H S Wang, T H Soong, Y K Changgeng-Yi-Xue-Za-Zhi. 1999 September; 22(3): 423-32

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Maternal education, breastfeeding behaviours and lactational amenorrhoea: studies among two ethnic communities in Ile Ife, Nigeria. Author(s): Obafemi Awolowo University, Ile Ife, Nigeria. [email protected] Source: Davies Adetugbo, A A Ojofeitimi, E O Nutr-Health. 1996; 11(2): 115-26 02601060

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Pharmacologic management of athletic amenorrhea. Author(s): Alabama Sports Medicine and Orthopedic Center, Birmingham, USA. Source: Fagan, K M Clin-Sports-Med. 1998 April; 17(2): 327-41 0278-5919

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Primary amenorrhoea and infertility due to a mutation in the beta-subunit of folliclestimulating hormone. Author(s): Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK. Source: Matthews, C H Borgato, S Beck Peccoz, P Adams, M Tone, Y Gambino, G Casagrande, S Tedeschini, G Benedetti, A Chatterjee, V K Nat-Genet. 1993 September; 5(1): 83-6 1061-4036

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Pulsatile intravenous GnRH treatment in hypothalamic amenorrhea. Author(s): Cattedra di Ginecologia ed Ostetricia, Universita degli Studi di Palermo. Source: Agrifoglio, V Alaimo, G Acta-Eur-Fertil. 1991 Nov-December; 22(6): 333-4 05872421

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Resumption of menstruation after amenorrhea in women treated by endometrial ablation and myometrial resection. Author(s): Department of Obstetrics and Gynecology, Columbia Michael Reese Hospital, 2929 South Ellis, Chicago, IL 60616, USA. Source: Seeras, R C Gilliland, G B J-Am-Assoc-Gynecol-Laparosc. 1997 May; 4(3): 305-9 1074-3804

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The efficacy of lisuride in the treatment of hyperprolactinemic amenorrhea. Author(s): Department of Obstetrics & Gynaecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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Source: Rojanasakul, A Sirimongkolkasem, R Chailurkit, L O J-Med-Assoc-Thai. 1990 February; 73 Suppl 142-6 0125-2208 •

The impact of dosage on ovulation induction by pulsatile gonadotropin-releasing hormone (Gn-RH) in hypothalamic amenorrhea. Author(s): Cattedra di Fisiopathologia della Riproduzione Umana, University of Cagliari, Italy. Source: Caruso, A Lanzone, A Fulghesu, A M Mancuso, S J-Endocrinol-Invest. 1987 October; 10(5): 513-6 0391-4097

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Treatment of reduced bone mineral density in athletic amenorrhea: a pilot study. Author(s): British Olympic Medical Centre, Harrow, Middlesex, UK. Source: Gibson, J H Mitchell, A Reeve, J Harries, M G Osteoporos-Int. 1999; 10(4): 284-9 0937-941X

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

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

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

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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/

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

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

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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

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

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

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

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

•

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

•

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

The following is a specific Web list relating to amenorrhea; 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 B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com

•

Minerals Acetyl-l-carnitine Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND AMENORRHEA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to amenorrhea. 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 amenorrhea 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 “amenorrhea” (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 amenorrhea: •

Active coping behavior, anxiety, and cortical steroid excretion in the prediction of transient amenorrhea. Author(s): Shanan J, Brzezinski A, Sulman F, Sharon M. Source: Behavioral Science. 1965 October; 10(4): 461-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5891280&dopt=Abstract

•

Amenorrhea associated with carotenemia. Author(s): Kemmann E, Pasquale SA, Skaf R. Source: Jama : the Journal of the American Medical Association. 1983 February 18; 249(7): 926-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6823046&dopt=Abstract

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Amenorrhea in patients with Hodgkin's disease treated with antineoplastic agents. Author(s): Sobrinho LG, Levine RA, DeConti RC.

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Source: American Journal of Obstetrics and Gynecology. 1971 January 1; 109(1): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5538962&dopt=Abstract •

Amenorrhea induced by adjuvant chemotherapy in early breast cancer patients: prognostic role and clinical implications. Author(s): Del Mastro L, Venturini M, Sertoli MR, Rosso R. Source: Breast Cancer Research and Treatment. 1997 April; 43(2): 183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9131274&dopt=Abstract

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Amenorrhoea in vegetarian athletes. Author(s): Slavin J, Lutter J, Cushman S. Source: Lancet. 1984 June 30; 1(8392): 1474-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6145917&dopt=Abstract

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Amenorrhoea, vegetarianism, and/or low fat. Author(s): Frisch RE. Source: Lancet. 1984 May 5; 1(8384): 1024. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6143952&dopt=Abstract

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Breastfeeding and postpartum amenorrhea in a traditional society: a hazards model analysis. Author(s): Nath DC, Singh KK, Land KC, Talukdar PK. Source: Soc Biol. 1993 Spring-Summer; 40(1-2): 74-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8146695&dopt=Abstract

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Breast-feeding patterns and lactational amenorrhoea among the Warli tribals: a socioanthropological inquiry. Author(s): Carneiro P. Source: Int J Fertil. 1988; 33 Suppl: 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2902024&dopt=Abstract

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Colpocytologic studies in amenorrhea treated by transcerebral electrostimulation. Author(s): Toth F, Gimes R, Fornadi F. Source: Acta Cytol. 1965 September-October; 9(5): 347-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5214052&dopt=Abstract

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Contraceptive efficacy of lactational amenorrhoea. Author(s): Kennedy KI, Visness CM. Source: Lancet. 1992 January 25; 339(8787): 227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1346183&dopt=Abstract

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Diet in athletic amenorrhoea. Author(s): Brooks SM, Sanborn CF, Albrecht BH, Wagner WW Jr. Source: Lancet. 1984 March 10; 1(8376): 559-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6142266&dopt=Abstract

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Diet, hormonal, and metabolic factors affecting bone mineral density in adolescent amenorrheic and eumenorrheic female runners. Author(s): Baer JT, Taper LJ, Gwazdauskas FG, Walberg JL, Novascone MA, Ritchey SJ, Thye FW. Source: The Journal of Sports Medicine and Physical Fitness. 1992 March; 32(1): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1405575&dopt=Abstract

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Discrepancies between genital responses and subjective sexual function during testosterone substitution in women with hypothalamic amenorrhea. Author(s): Tutten A, Laan E, Panhuysen G, Everaerd W, de Haan E, Koppeschaar H, Vroon P. Source: Psychosomatic Medicine. 1996 May-June; 58(3): 234-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8771623&dopt=Abstract

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Emotional settings of functional amenorrhea. Author(s): ENGELS WD, PATTEE CJ, WITTKOWER ED. Source: Psychosomatic Medicine. 1964 November-December; 26: 682-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14230411&dopt=Abstract

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Energy and nutrient status of amenorrheic athletes participating in a diet and exercise training intervention program. Author(s): Kopp-Woodroffe SA, Manore MM, Dueck CA, Skinner JS, Matt KS. Source: Int J Sport Nutr. 1999 March; 9(1): 70-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200061&dopt=Abstract

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Herbal medicine (Shakuyaku-kanzo-to) in the treatment of risperidone-induced amenorrhea. Author(s): Yamada K, Kanba S, Yagi G, Asai M. Source: Journal of Clinical Psychopharmacology. 1999 August; 19(4): 380-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440470&dopt=Abstract

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Historical note on the treatment of amenorrhea with water pepper. Author(s): Gifford RR. Source: J Reprod Med. 1972 September; 9(3): 143-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4561655&dopt=Abstract

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Integrating the Lactational Amenorrhea Method into a family planning program in Ecuador. Author(s): Wade KB, Sevilla F, Labbok MH. Source: Stud Fam Plann. 1994 May-June; 25(3): 162-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7940621&dopt=Abstract

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Lactation, nutrition, and postpartum amenorrhea in lowland Papua New Guinea. Author(s): Tracer DP. Source: Human Biology; an International Record of Research. 1996 April; 68(2): 277-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8838917&dopt=Abstract

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Maternal education, breastfeeding behaviours and lactational amenorrhoea: studies among two ethnic communities in Ile Ife, Nigeria. Author(s): Davies-Adetugbo AA, Ojofeitimi EO. Source: Nutr Health. 1996; 11(2): 115-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8994235&dopt=Abstract

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Metaphoric hypnotic imagery in the treatment of functional amenorrhea. Author(s): van der Hart O. Source: Am J Clin Hypn. 1985 January; 27(3): 159-65. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3976546&dopt=Abstract

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Nutritional aspects of amenorrhea in the female athlete triad. Author(s): Benson JE, Engelbert-Fenton KA, Eisenman PA. Source: Int J Sport Nutr. 1996 June; 6(2): 134-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8744786&dopt=Abstract

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Pharmacologic management of athletic amenorrhea. Author(s): Fagan KM. Source: Clinics in Sports Medicine. 1998 April; 17(2): 327-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9580845&dopt=Abstract

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Prospective study of the hypothalamic-pituitary axis in thalassaemic patients who developed secondary amenorrhoea. Author(s): Chatterjee R, Katz M, Cox TF, Porter JB. Source: Clinical Endocrinology. 1993 September; 39(3): 287-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8222291&dopt=Abstract

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Psychiatric aspects of acquired amenorrhea. report of 4 cases. Author(s): CHEZ R, PASNAU R, LEIKEN S, BATISTE C.

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Source: Obstetrics and Gynecology. 1964 October; 24: 549-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14218001&dopt=Abstract •

Psychogenic factors in anovulatory women. III. Behavioral and psychoanalytic aspects of anovulatory amenorrhea. Author(s): LOFTUS TA. Source: Fertility and Sterility. 1962 January-February; 13: 20-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14466283&dopt=Abstract

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Psychological correlates of the development of amenorrhea in a stress situation. Author(s): Osofsky HJ, Fisher S. Source: Psychosomatic Medicine. 1967 January-February; 29(1): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5340272&dopt=Abstract

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Psychosomatic amenorrhea. Author(s): SCHWARTZ HA. Source: Psychosomatics. 1963 July-August; 4: 222-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13987371&dopt=Abstract

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Secondary amenorrhea. Author(s): GREENBLATT RB, PUEBLE RA, FAUCHER GL. Source: Mod Treat. 1965 January; 90: 135-44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14257797&dopt=Abstract

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The cytology of amenorrhoea. Author(s): Wachtel E. Source: Acta Cytol. 1966 January-February; 10(1): 56-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5220491&dopt=Abstract

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Treating amenorrhea in vital energy-deficient patients with angelica sinensisastragalus membranaceus menstruation-regulating decoction. Author(s): He ZP, Wang DZ, Shi LY, Wang ZQ. Source: J Tradit Chin Med. 1986 September; 6(3): 187-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3807414&dopt=Abstract

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Treatment of functional hypothalamic amenorrhea with hypnotherapy. Author(s): Tschugguel W, Berga SL. Source: Fertility and Sterility. 2003 October; 80(4): 982-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556821&dopt=Abstract

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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/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to amenorrhea; 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: Healthnotes, Inc.; www.healthnotes.com Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com

•

Chinese Medicine Biejia Alternative names: Turtle Shell; Carapax Trionycis Source: Chinese Materia Medica

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Chongweizi Alternative names: Motherwort Fruit; Fructus Leonuri Source: Chinese Materia Medica Chuanmutong Alternative names: Armand Clematis Stem; Caulis Clematidis Armandii Source: Chinese Materia Medica Chuanniuxi Alternative names: Medicinal Cyathula Root; Radix Cyathulae Source: Chinese Materia Medica Chuanshanjia Alternative names: Pangolin Scale; Squama Manitis Source: Chinese Materia Medica Chuanxiong Alternative names: Szechwan Lovage Rhizome; Rhizoma Chuanxiong Source: Chinese Materia Medica Dahuang Alternative names: Rhubarb; Radix et Rhizoma Rhei Source: Chinese Materia Medica Dahuang Zhechong Wan Alternative names: Dahuang Zhechong Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Danggui Alternative names: Chinese Angelica; Radix Angelicae Sinensis Source: Chinese Materia Medica Danshen Alternative names: Danshen Root; Radix Salviae Miltiorrhizae Source: Chinese Materia Medica Daxueteng Alternative names: Sargentgloryvine Stem; Caulis Sargentodoxae Source: Chinese Materia Medica Ezhu Alternative names: Zedoray Rhizome; Rhizoma Curcumae Source: Chinese Materia Medica Fuke Tongjing Wan Alternative names: Fuke Tongjing Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China

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Ganqi Alternative names: Dried Lacquer; Resina Toxicodendri Source: Chinese Materia Medica Guanmutong Alternative names: Manchurian Dutchmanspipe Stem; Caulis Aristolochiae Manshuriensis Source: Chinese Materia Medica Guizhi Alternative names: Cassia Twig; Ramulus Cinnamomi Source: Chinese Materia Medica Heizhongcaozi Alternative names: Fennelflower Seed; Semen Nigellae Source: Chinese Materia Medica Honghua Alternative names: Safflower; Flos Carthami Source: Chinese Materia Medica Huzhang Alternative names: Giant Knotweed Rhizome; Rhizoma Polygoni Cuspidati Source: Chinese Materia Medica Jianghuang Alternative names: Turmeric; Rhizoma Curcumae Longae Source: Chinese Materia Medica Jixingzi Alternative names: Garden Balsam Seed; Semen Impatientis Source: Chinese Materia Medica Juanbai Alternative names: Spikemoss; Herba Selaginellae Source: Chinese Materia Medica Lingxiaohua Alternative names: Trumpetcreeper Flower; Flos Campsis Source: Chinese Materia Medica Lulutong Alternative names: Beautiful Sweetgum Fruit; Fructus Liquidambaris Source: Chinese Materia Medica Mabiancao Alternative names: European Verbena Herb; Herba Verbanae Source: Chinese Materia Medica Mudanpi Alternative names: Tree Peony Bark; Cortex Moutan Source: Chinese Materia Medica

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Niuxi Alternative names: Twotoothed Achyranthes Root; Radix Achyranthis Bidentatae Source: Chinese Materia Medica Pianjianghuang Alternative names: Wenyujin Concise Rhizome; Rhizoma Wenyujin Concisum Source: Chinese Materia Medica Puhuang Alternative names: Cattail Pollen; Pollen Typhae Source: Chinese Materia Medica Qiancao Alternative names: Longtube Ground Ivy Herb; Lianqiancao; Herba Glechomae Source: Chinese Materia Medica Qianjinzi Alternative names: Caper Euphorbia Seed; Semen Euphorbiae Source: Chinese Materia Medica Qumai Alternative names: Lilac Pink Herb; Herba Dianthi Source: Chinese Materia Medica Rougui Alternative names: Cassia Bark; Cortex Cinnamomi Source: Chinese Materia Medica Sanleng Alternative names: Common Burreed Tuber; Rhizoma Sparganii Source: Chinese Materia Medica Shaii Alternative names: Seabuckthorn Fruit; Fructus Hippophae Source: Chinese Materia Medica Shanzha Alternative names: Hawthorn Fruit; Fructus Crataegi Source: Chinese Materia Medica Shexiang Alternative names: Musk; Moschus Source: Chinese Materia Medica Shiyiwei Nengxiao Wan Alternative names: Shiyiwei Nengxiao Pills; Shiyiwei Nengxiao Wan (Shi Yi Wei Neng Xiao Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China

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Shuizhi Alternative names: Leech; Hirudo Source: Chinese Materia Medica Sumu Alternative names: Sappan Wood; Lignum Sappan Source: Chinese Materia Medica Taoren Alternative names: English Walnut Seed; Hetaoren; Semen Juglandis Source: Chinese Materia Medica Tubiechong Alternative names: Ground Beetle; Eupolyphaga seu Steleophaga Source: Chinese Materia Medica Xiangfu Alternative names: Nutgrass Galingale Rhizome; Rhizoma Cyperi Source: Chinese Materia Medica Xiaoyelian Alternative names: Common Sinopodophyllum Fruit; Fructus Podophylli Source: Chinese Materia Medica Yimucao Alternative names: Motherwort Herb; Herba Leonuri Source: Chinese Materia Medica Yimucao Gao Alternative names: Concentrated Decoction of Motherwort Herb; Yimucao Gao Extractum Leonuri Inspissatum Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Yujin Alternative names: Turmeric Root Tuber; Radix Curcumae Source: Chinese Materia Medica Yuzhizi Alternative names: Akebia Fruit; Fructus Akebiae Source: Chinese Materia Medica Zelan Alternative names: Hirsute Shiny Bugleweed Herb; Herba Lycopi Source: Chinese Materia Medica Zhizi Alternative names: Cape Jasmine Fruit; Fructus Gardeniae Source: Chinese Materia Medica

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•

Herbs and Supplements Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Blue Cohosh Alternative names: Caulophyllum thalictroides Source: Healthnotes, Inc.; www.healthnotes.com Chasteberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,767,00.html Dong Quai (Angelica) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,774,00.html Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Medroxyprogesterone Source: Healthnotes, Inc.; www.healthnotes.com Motherwort Alternative names: Leonurus cardiaca Source: Healthnotes, Inc.; www.healthnotes.com Perphenazine Source: Healthnotes, Inc.; www.healthnotes.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Risperidone Source: Healthnotes, Inc.; www.healthnotes.com Thioridazine Source: Healthnotes, Inc.; www.healthnotes.com Vitex Alternative names: Chaste; Vitex agnus-castus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitex Alternative names: Vitex agnus-castus Source: Healthnotes, Inc.; www.healthnotes.com

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Yarrow Alternative names: Achillea millefolium Source: Healthnotes, Inc.; www.healthnotes.com

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.

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CHAPTER 4. DISSERTATIONS ON AMENORRHEA Overview In this chapter, we will give you a bibliography on recent dissertations relating to amenorrhea. 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 “amenorrhea” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on amenorrhea, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Amenorrhea 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 amenorrhea. 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: •

Breastfeeding Patterns, Nutrition and Postpartum Amenorrhea in Guatemalan Women: A Multi-State Hazard Approach by Pinto-Aguirre, Guido, PhD from The University of Wisconsin - Madison, 1994, 315 pages http://wwwlib.umi.com/dissertations/fullcit/9508876

•

Postpartum Amenorrhea: Behavioral and Socio-Demographic Correlates (Breastfeeding) by Lee, Lily Waiyee, PhD from University of California, Berkeley, 1985, 249 pages http://wwwlib.umi.com/dissertations/fullcit/8525031

•

Relationship among Calcium Intake, Secondary Amenorrhea and Stress Fractures in Female College Cross Country/Track Athletes by Doyle, Robert, PhD from Southern Illinois University at Carbondale, 1987, 97 pages http://wwwlib.umi.com/dissertations/fullcit/8728268

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•

The Effects of Women's Education on Postpartum Nonsusceptible Period in Ilorin, an Urban Community in Nigeria (Breastfeeding, Abstinence, Amenorrhea) by Oni, Gbolahan A., PhD from The Johns Hopkins University, 1985, 374 pages http://wwwlib.umi.com/dissertations/fullcit/8518518

•

The Role of Body Fat in the Etiology of Athletic Amenorrhea by Sanborn, Charlotte Feicht, PhD from University of Colorado at Boulder, 1983, 114 pages http://wwwlib.umi.com/dissertations/fullcit/8400929

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.

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

Recent Trials on Amenorrhea The following is a list of recent trials dedicated to amenorrhea.5 Further information on a trial is available at the Web site indicated. •

Ovarian Follicle Function in Patients with Premature Ovarian Failure Condition(s): Amenorrhea; Hypoaldosteronism; Hypogonadism; Infertility; Premature Ovarian Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Premature ovarian failure may be the result of the destruction of eggs in the ovaries. Some patients experience complete destruction of all eggs within the ovaries. In these cases, no treatment will restore egg development. However, some patients experience a condition known as premature autoimmune ovarian failure. In these cases eggs still remain in the ovaries, but they are prevented from working normally by the body's own immune system. This study was designed to evaluate patients with premature ovarian failure. It will provide researchers with information that may be used later in other studies related to this condition. In addition, patients participating in this study may be selected for other studies that may benefit them directly. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001275

5

These are listed at www.ClinicalTrials.gov.

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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 “amenorrhea” (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/

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

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

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

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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

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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

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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

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

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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/

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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

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

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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

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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

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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

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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

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CHAPTER 6. PATENTS ON AMENORRHEA 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.6 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 “amenorrhea” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on amenorrhea, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Amenorrhea By performing a patent search focusing on amenorrhea, 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 6Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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

2-(4-Hydroxyalkyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives Inventor(s): Bagli; Jehan F. (Kirkland, CA), Bogri; Tibor (Montreal, CA), Voith; Katherine (Dorval, CA) Assignee(s): Ayerst, Mckenna & Harrison, Inc. (montreal, Ca) Patent Number: 4,469,695 Date filed: February 25, 1980 Abstract: 2-(4-Hydroxyalkyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions of the derivatives are disclosed. The derivatives exhibit dopamine-receptor stimulating activity in a mammal and are useful for treating hyperprolactinemia, galactorrhea, amenorrhea, impotence, Parkinsonism, diabetes, acromegaly, hypertension and other central nervous system disorders. Excerpt(s): This invention relates to novel 2-(4-hydroxyalkyl-1-piperazinyl)-2,4,6cycloheptatrien-1-one derivatives, to therapeutically acceptable acid addition salts thereof, to a process for their preparation, to methods of using the derivatives and to pharmaceutical compositions of the derivatives. These derivatives exhibit dopaminereceptor stimulating activity in a mammal. Thus, they can be useful for treating hyperprolactinemia, galactorrhea, amenorrhea, impotence, Parkinsonism, diabetes, acromegaly, hypertension and other central nervous system disorders which respond to dopamine-receptor stimulation. The following references were obtained from a literature search for 2-substituted tropones: E. Sianesi et al., J. Med. Chem., 10, 1144 (1967); G. Biggi et al., J. Amer. Chem. Soc., 94, 4700 (1972); T. Toda et al., Chem. Abstr., 76, 72185f (1972) for Bull. Chem. Soc. Jap., 45, 226 (1972); G. Biggi et al., J. Amer. Chem. Soc., 95, 7101 (1973); C. A. Veracini et al., J. Chem. Soc. Commun., 623 (1974); B. J. Abadir et al., J. Chem. Soc., 2350 (1952) and T. Nozoe et al., Chem. Abstr., 70, 87244z (1969) for Bull. Chem. Soc. Jap., 41, 2978 (1968). These references disclose compounds which like the compounds of this invention are 2,4,6-cycloheptatrien-1-one derivatives. Of these 2,4,6-cycloheptatrien-1-one derivatives, the 2-piperidinyl-2,4,6-cycloheptatrien-1-one described by G. Biggi et al., J. Amer. Chem. Soc., 94, 4700 (1972), cited above, can be considered the most closely related to the compounds of this invention. However, the latter 2-piperidinyl derivative is treated as a chemical curiosity without any indicated useful pharmacological activity. Furthermore, the compounds of this invention differ from the compounds of Biggi et al by having a 1-piperazinyl group at position 2 of the 2,4,6-cycloheptatrien-1-one ring. A preferred group of compounds of this invention is represented by formula I in which Alk is a trivalent alkylene having one to six carbon atoms; R.sup.1 is hydrogen or methyl; R.sup.2 and R.sup.3 each is hydrogen or lower alkyl having one to three carbon atoms, R.sup.4 is hydrogen, phenyl, hydroxy, phenoxy, phenyl mono-, di- or trisubstituted with methylsulfonylamino, lower alkoxy or hydroxy, or phenoxy mono-, di- or trisubstituted with lower alkyl or halo; and R.sup.5 represents a substituent at position 7 of the 2,4,6-cycloheptatrien-1-one ring and is selected from hydrogen, halo, lower alkyl, lower alkoxy, trifluoromethyl, or 1-oxo(lower)alkylamino; with the proviso that when R.sup.4 is hydroxy, the hydroxy groups are joined to different carbon atoms; or a therapeutically acceptable acid addition salt thereof. Web site: http://www.delphion.com/details?pn=US04469695__

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2-oxo-pyrido[2,3-g]quinoline derivatives Inventor(s): Schaus; John M. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (indianapolis, In) Patent Number: 4,939,259 Date filed: July 24, 1989 Abstract: Trans-(.+-.)-2-(substituted)-6-(substituted)-5,5a,6,7,8,9,9a,10-octahydroph rido[2,3-g]quinolines are useful in treating a variety of disorders including Parkinsonism, anxiety, depression, hypertension, glaucoma, sexual dysfunction, and prolactin mediated disorders such as galactorrhea, amenorrhea, prolactinoma and the inhibition of postpartum lactation. Excerpt(s): Certain substituted ergolines are known to be D-2 dopamine agonists having the ability to inhibit the secretion of prolactin and to affect favorably the symptoms of Parkinson's Syndrome. For example, in the foregoing structure when R is n-propyl, R.sup.1 is methylthiomethyl, and R.sup.2 is H, the substituted ergoline has been given the generic name pergolide, which is disclosed in U.S. Pat. No. 4,166,182. Pergolide has been proven to be effective in the treatment of some symptoms of Parkinsonism, and is being developed as the mesylate salt. Another such ergoline drug is.alpha.bromoergocryptine, named generically as bromocryptine. It is disclosed in U.S. Pat. Nos. 3,752,814 and 3,752,888. For bromocryptine, R.sup.2 is Br, R is methyl and R' is the ergocryptine side chain. While both ergolines are D-2 dopamine agonists, bromocryptine, and to a lesser extent pergolide, also have some.alpha.-blocking activity. This invention provides new octahydropyrido[2,3-g]quinolines having various substituents at the 2- and 6-positions of the compounds. The compounds of the invention are useful for the treatment of a variety of disorders including Parkinsonism, depression, hypertension, anxiety, glaucoma, sexual dysfunction and prolactin mediated disorders such as galactorrhea, amenorrhea, prolactinoma and the inhibition of post-partum lactation. R is C.sub.1 -C.sub.4 alkyl, allyl, or cyclopropylmethyl; and pharmaceutically-acceptable salts thereof. Web site: http://www.delphion.com/details?pn=US04939259__

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Condensed-ring thiophene derivatives, their production and use Inventor(s): Choh; Nobuo (Ibaraki, JP), Furuya; Shuichi (Ibaraki, JP), Hinuma; Shuji (Ibaraki, JP), Kato; Koichi (Ibaraki, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 5,817,819 Date filed: June 16, 1995 Abstract: A gonadotropin-releasing hormone antagonistic composition, which comprises an optionally substituted condensed-bicyclic compound consisting of a homo or hetero 5 to 7 membered ring and a homo or hetero 5 to 7 membered ring is effective as a propylactic or therapeutic agent for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, cancer of uterine cervix, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; is effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a

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menstrual cycle controlling agent); can be used as a contraceptive of male or female, as an ovulation-inducing agent of female; can be used as an infertility treating agent by using a rebound effect owing to a stoppage of administration thereof; is useful as modulating estrous cycles in animals in the field of animal husbandry, as an agent fro improving the quality of edible meat or promoting the growth of animals; is useful as an agent of spawning promotion in fish. Excerpt(s): The present invention relates to a pharmaceutical composition for antagonizing a gonadotropin-releasing hormone (GnRH) containing a condensedbycyclic compound consisting of a homo or hetero 5 to 7-membered ring group and a homo or hetero 5 to 7-membered ring group. The present invention also relates to novel condensed-ring hiophene derivatives and salts thereof. The present invention further relates to methods for manufacturing the novel condensed-ring thiophene derivatives and the salts thereof. Secretion of anterior pituitary hormone undergoes the control by peripheral hormone secreted from target organs for the respective hormones and by secretion-accelerating or -inhibiting hormone from hypothalamus, which is the upper central organ of anterior lobe of pituitary (in this specification, these hormones are collectively called "hypothalamic hormone"). At the present stage, as hypothalamic hormones, nine kinds of hormones including, for example, thyrotropin releasing hormone (TRH) or gonadotropin releasing hormone {GnRH: sometimes called as LHRH (luteinizing hormone releasing hormone)} are confirmed their existence (cf. Seirigaku 2, compiled by M. Iriku and K Toyama, published by Bunkohdo, p610-618, 1986). These hypothalamic hormones are assumed to show their actions via the receptor which is considered to exist in the anterior lobe of pituitary (cf. ibid), and observatinal studies of receptor genes specific to these hormones, including cases of human, have been developed (Receptor Kiso To Rinsho, compiled by H. Imura, et al., published by Asakura Shoten, p297-304, 1993). Accordingly, antagonists or agonists specifically and selectively acting on these receptors control the action of hypothalamic hormone and controlling the secretion of anterior pituitary hormone. As the results, they are expected to be useful for prophylactic and therapeutic agents of anterior pituitary hormone dependent diseases. Leuprorelin acetate ›Fujino et al., Biological and Biophysical Research Communications, Vol.60, 00.406-413, 1974); Oliver, R. T. D. et al., British Journal of Cancers, Vol.59, p.823, 1989; and Toguchi et al., Journal of International Medical Research, Vol.18, pp.35-41!, which is a highly potent derivative of gonadotropic hormone-releasing hormone, one of the hypothalamic hormones, (hereinafter sometimes abbreviated as GnRH) ›Schally A. V. et at., Journal of Biological Chemistry, Vol. 246, pp.7230-7236, 1971; and Burgus, R. et al., Proceeding of Natural Academic Science, USA, Vol.69, pp278-282, 1972!, by administration of multiple doses, lowers release,production of gonadotropic hormone in pituitary, causing lowering of reactivity on gonadotropic hormone is spermary and ovary to suppress secretion of testosterone and estrogen. Leuprorelin acetate has, therefore, been known to show antitumor activity on such hormone-dependent cancers as exemplified by prostate cancer, and has been widely used in the clinical field. Leuprorelin acetate has been widely used clinically also as a therapeutic agent of e.g. endometriosis and precocious puberty. The high antitumor activity of leuprorelin acetate is assumed to be due to its high resistance, as compared with natural GnRH, against protease,and to high affinity to GnRH receptor causing desensitization of GnRH due to decrease in number of receptors. However, as leuprorelin acetate is an ultra-agonist on GnRH receptor, it has been known that, immediately after the first administration, a transient aggravation accompanied with the rise of serum testosterone concentration due to pituitary-gonadotropic action (acute action) is observed. Circumstances being such as above, GnRH antagonistic drugs which are expected to have substantially the same therapeutic effects as described above but

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not to cause the above-mentioned transient pituitary-gonadotropic action (acute action) have been desired. As compounds having such GnRH antagonistic activity, a number of compounds including, for example, derivatives of GnRH such as straight-chain peptides, (U.S. Pat. No. 5140009, 5171835), cyclic hexapeptide derivatives ›JPA S61(1986)-191698! or bicyclic peptide derivatives ›Journal of medicinal chemistry, Vol.36, pp.3265-3273, 1993!. These compounds are, however, all peptides, which leave many problems including, for example, dosage forms, stability of drugs, durability of actions and stability on metabolism. For solving these problems, orally administrable GnRH antagonistic drugs, especially non-peptide ones, are strongly desired. At the present stage, however, no report on non-peptide GnRH antagonistic drugs has been made. Web site: http://www.delphion.com/details?pn=US05817819__ •

Device for the intermittent pulsatory application of fluid medicaments Inventor(s): Eschweiler; Wilhelm (Rammsee, DE), Leyendecker; Gerhard (Bonn-BadGodesberg, DE) Assignee(s): Ferring Arzneimittel Gmbh (kiel, De) Patent Number: 4,397,639 Date filed: April 23, 1981 Abstract: A device for the intermittent pulsatory application of fluid medicaments, particular for the application of LH-RH for initiating ovulation in women having hypothalamic and hyperprolactinamic amenorrhea. Said device has a reservoir for the medicament and a hose connected to said reservoir for delivering said medicament to a patient, which reservoir and which hose are a prefabricated unit which can be inserted into the device and removed when the content of the reservoir is exhausted. Furthermore, said device has a roller-type pump acting onto said hose when it is stretched onto the needle-like rollers of said roller-type pump, and a D.C. motor for driving said pump and further control means for controlling said motor, said control means having a timer for pulse and pause times so that the motor is energized only for short periods not longer than several minutes while it is between each two of such running periods stopped for more than one hour. At least one battery is provided as energy source for the D.C. motor. Excerpt(s): The invention relates to a device for the intermittent pulsatory application of fluid medicaments, particularly for the application of LH-RH for initiating ovulation in women having hypothalamic and hyperprolactinamic amenorrhea. In patients having hypothalamic and hyperprolactinamic amenorrhea the best treatment results are obtained when the pulsation of the natural secretion of LH-RH is simulated at intervals of 90 minutes between the individual doses of the medicament to initiate ovulation. It is known to feed metered quantities of fluid and/or gaseous medicaments by means of devices which are driven by electric motors and which are provided with means for interchangeable programmes. A mechanically controlled device for continuous infusion of medicaments is disclosed in Austrian Pat. No. 210 558. Furthermore, German Auslegeschrift No. 1 491 747 discloses an injection device for single injection of a roentgen contrast agent, wherein the injected quantity, the rate and, if required, a time delay can be controlled by means of an electrical programme transmitter. Web site: http://www.delphion.com/details?pn=US04397639__

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Prevention of endometriosis signs or symptons Inventor(s): Heinrichs; William LeRoy (8 Campbell La., Menlo Park, CA 94025) Assignee(s): None Reported Patent Number: 6,265,393 Date filed: August 7, 1998 Abstract: Methods and articles of manufacture are provided for the long-term prevention of clinical symptoms and signs produced by endometriosis. Such methods and articles of manufacture involve the continuous coadministration of low doses of an estrogen agent and a progestin agent to maintain an induced state of oligomenorrhea or amenorrhea in an afflicted woman. Excerpt(s): The present invention relates to the coadministration of an estrogen agent and a progestin agent in low doses for the long-term prevention of endometriosis signs or symptoms. Many women, approximately 5-10 percent of those in their reproductive years, are afflicted with endometriosis and suffer progressive, disabling dysmenorrhea and pelvic pain around the time of their menses (Brosens, Endometriosis-A Disease Because it is Characterized by Bleeding, Am. J. Obstet. Gynecol. 176:263-7 (1997)). In addition, pelvic pain unassociated with menses may restrict afflicted women to measured participation in athletic and other physical activities, such as dancing and hiking. Through dyspareunia, they suffer not only the pain and often-missed orgasmic fulfillment, but also the doubts of sincerity and the cautious love of their sexual partners, perhaps even marital discord, separation, or infertility. Through relative infertility, they suffer further reductions in self-esteem from the pangs of guilt and failure engendered by struggles to conceive, suffering that adds personal, physical, and economic cost. Often, coital events or pelvic exams produce pelvic aching for hours or even days thereafter. The peri-menstrual pain experienced by afflicted women may be relieved in part by non-steroidal anti-inflanmmatory drugs (NSAID's). But those not benefitted adequately require ovulation-suppressing treatments, or finally laparoscopy, where the majority are discovered to have the findings typical of endometriosis, i.e., ectopic `implants` of endometrial tissue on the peritoneal surface of the pelvis or extragenital areas. Others with unexplained infertility have similar findings. Web site: http://www.delphion.com/details?pn=US06265393__

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Prolactin production inhibitory agent Inventor(s): Furuya; Shuichi (Ibaraki, JP), Matsumoto; Hirokazu (Ibaraki, JP), Suzuki; Nobuhiro (Ibaraki, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 5,977,132 Date filed: December 9, 1996 Abstract: The prolactin production inhibition agent of the present invention containing a condensed cyclic compound, which is characterized by containing a condensed bicyclic structure of an optionally substituted homo or hetero 5- to 7-membered ring with an optionally substituted homo or hetero 5- to 7-membered ring, or a salt thereof, can be used, as a medicine, for the prophylaxis or therapy of diseases accompanied with an excess prolactin production or diseases having enhanced reactivity with prolactin, or is useful for inhibiting puerperal lactation, and also useful as a prophylactic or therapeutic

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agent of galactorrhea, hyperprolactinemic ovulation disturbance, amenorrheagalactorrhea syndrome, prolactinoma, and besides, interbrain tumor, and acromegaly, pituitary gigantism. Excerpt(s): This application claims priority to Japanese Patent Application Japan 3450461995, filed Dec. 8,1995. The present invention relates to a prolactin production inhibitory composition containing a condensed cyclic compound, especially containing at least a condensed bicyclic structure, or a salt thereof; a method for treating a mammal suffering from hyperprolactinemia; and a use of a condensed cyclic compound for producing a prolactin production inhibitory composition for treating a mammal suffering from hyperprolactinemia. Prolactin, which is produced and secreted from anterior lobe of the pituitary gland, shows a variety of actions including the actions on mammary glands to play an important role for starting and maintenance of lactation, the actions on waterelectrolyte metabolism, the actions on reproductive glands, the actions on the immune system and the actions on brain function. The prolactin-producing cells of the pituitary gland are recognized to have clearly characteristic properties. For example, peptide hormones so far known as various pituitary hormone secretion/production stimulating hormones secreted from hypothalamus are clearly observed to act preferentially and specifically on specified pituitary hormone secretion/production cells of the anterior lobes of the pituitary gland. Typically, while gonadotropic hormone releasing hormone, sometimes referred to as GnRH (gonadotropin releasing hormone): lutenizing hormonereleasing hormone (LH-RH), acts preferentially and specifically on the cells which secrete/produce, for example, follicle stimulating hormone (FSH) and lutenizing hormone (LH) in the anterior lobe of pituitary, no observational studies have been reported that the GnRH acts on the cells which produce/secrete prolactin, also known as an anterior pituitary hormone, to cause secretion of prolactin. Therefore, cells which produce/secrete gonadotropins and prolactin are considered to have, among anterior pituitary hormone secreting/producing cells, entirely different characteristic features. From the viewpoints as above, for controlling the prolactin production/secretion, the drug to be used therefor should at least act on pituitary prolactin-producing cells which can be clearly distinguished from other peptide hormone secretion/production cells of pituitary. Web site: http://www.delphion.com/details?pn=US05977132__ •

Quinoline derivatives, their production and use Inventor(s): Choh; Nobuo (Tsukuba, JP), Furuya; Shuichi (Tsukuba, JP), Sasaki; Satoshi (Tsukuba, JP) Assignee(s): Takeda Chemical Industries Ltd. (osaka, Jp) Patent Number: 6,087,503 Date filed: September 14, 1998 Abstract: The present compounds are intermediates for the preparation of quinoline derivatives and compositions having gonadotropin-releasing hormone antagonistic activity useful as propylactics or therapeutic agent for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, uterine or cervical cancer, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; are effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a menstrual cycle controlling agent); can be used as a male or female contraceptive,

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as an ovulation-inducing agent; can be used as an infertility treating agent by using a rebound effect owing to a stoppage of administration thereof; and are useful for modulating estrous cycles in animals in the field of animal husbandry, as agents for improving the quality of edible meat or promoting the growth of animals, and as agents for promoting spawning in fish. Excerpt(s): The present invention relates to novel quinoline derivatives and salts thereof. The present invention further relates to methods for manufacturing these quinoline derivatives and the salts thereof, and pharmaceutical compositions containing the quinoline derivatives. Secretion of anterior pituitary hormone is controlled by peripheral hormones secreted from target organs for the respective hormones and by secretion-accelerating or -inhibiting hormones from the hypothalamus, which is the upper central organ of the anterior lobe of the pituitary (in this specification, these hormones are collectively called "hypothalamic hormones"). At the present stage, nine kinds of hormones have been confirmed as hypothalamic hormones, including, for example, thyrotropin releasing hormone (TRH) or gonadotropin releasing hormone {GnRH: sometimes called LH-RH (luteinizing hormone releasing hormone)} (cf. Seirigaku 2, compiled by M. Iriku and K Toyama, published by Bunkohdo, pp.610-618, 1986). These hypothalamic hormones are assumed to show their actions via the receptor which is considered to exist in the anterior lobe of the pituitary (cf. ibid), and studies of receptor genes specific to these hormones, including those of humans, have been developed (Receptor Kiso To Rinsho, compiled by H. Imura, et al., published by Asakura Shoten, pp.297-304, 1993). Accordingly, antagonists or agonists specifically and selectively acting on these receptors control the action of hypothalamic hormone and the secretion of anterior pituitary hormone. As a result, they are expected to be useful as prophylactic and therapeutic agents of anterior pituitary hormone dependent diseases. As compounds having GnRH antagonistic activity, a number of compounds including, for example, derivatives of GnRH such as straight-chain peptides, (U.S. Pat. No. 5,140,009 and No. 5,171,835), cyclic hexapeptide derivatives [Japanese Patent Application Laid-open No. 61(1986)-191698) or bicyclic peptide derivatives [Journal of medicinal chemistry, Vol.36, pp.3265-3273, 1993] have been disclosed. Web site: http://www.delphion.com/details?pn=US06087503__ •

Thienopyridine derivatives, their production and use Inventor(s): Furuya; Shuichi (Tsukuba, JP), Hayase; Yoji (Tsukuba, JP), Imada; Takashi (Tsukuba, JP), Matsumoto; Hirokazu (Tsukuba, JP), Suzuki; Nobuhiro (Tsukuba, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 6,001,850 Date filed: August 14, 1997 Abstract: The present thienopyridine derivatives and composition having gonadotropinreleasing hormone antagonistic activity are useful as prophylactic or therapeutic agents for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, cancer of uterine cervix, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; is effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a menstrual cycle controlling agent); is useful as a contraceptive of male or female, as an ovulation-inducing agent of female; is useful as an infertility treating agent by using a rebound effect owing to a stoppage of

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administration thereof; is useful as modulating estrous cycles in animals in the field of animal husbandry, as an agent for improving the quality of edible meat or promoting the growth of animals; is useful as an agent of spawning promotion in fish. Excerpt(s): The present invention relates to novel 4,7-dihydro-4-oxothieno[2,3b]pyridine derivatives and salts thereof. The present invention further relates to method for manufacturing these 4,7-dihydro-4-oxothieno[2,3-b]pyridine derivatives and salts thereof, and pharmaceutical composition containing these 4,7-dihydro-4-oxothieno[2,3b]pyridine derivatives and salts thereof. Secretion of anterior pituitary hormone undergoes the control by peripheral hormone secreted from target organs for the respective hormones and by secretion-accelerating or secretion-inhibiting hormone from hypothalamus, which is the upper central organ of anterior lobe of pituitary (in this specification, these hormones are collectively called "hypothalamic hormone"). At the present stage, as hypothalamic hormones, nine kinds of hormones including, for example, thyrotropin releasing hormone (TRH) or gonadotropin releasing hormone {GnRH: sometimes called as LH-RH (luteinizing hormone releasing hormone)} are confirmed their existence. These hypothalamic hormones are assumed to show their actions via the receptor which is considered to exist in the anterior lobe of pituitary, and observational studies of receptor genes specific to these hormones, including cases of human, have been developed. Accordingly, antagonists or agonists specifically and selectively control the action of hypothalamic hormone by acting on these receptors and control the secretion of anterior pituitary hormone. As the results, they are expected to be useful for prophylactic and therapeutic agents of anterior pituitary hormone dependent diseases. As compounds having such GnRH antagonistic activity, a number of compounds including, for example, derivatives of GnRH such as straight-chain peptides (U.S. Pat. No. 5,140,009, U.S. Pat. No. 5,171,835), cyclic hexapeptide derivatives (Japanese Patent Application Laid-open No.S61(1986)-191698) or bicyclic peptide derivatives (Journal of Medicinal Chemistry, Vol.36, pp.3265-3273, 1993). Furthermore, as non-peptide compounds having such GnRH antagonistic activity, compounds described in PCT International Publication No. WO 95/28405 are known. Web site: http://www.delphion.com/details?pn=US06001850__

Patent Applications on Amenorrhea As of December 2000, U.S. patent applications are open to public viewing.7 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 amenorrhea:

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

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Combination regimens using 3,3-substituted indoline derivatives Inventor(s): Edwards, James P.; (San Diego, CA), Fensome, Andrew; (Wayne, PA), Grubb, Gary S.; (Newtown Square, PA), Jones, Todd K.; (Solana Beach, CA), Tegley, Christopher M.; (Thousand Oaks, CA), Ullrich, John W.; (Exton, PA), Wrobel, Jay E.; (Lawrenceville, NJ), Zhi, Lin; (San Diego, CA) Correspondence: Howson And Howson; One Spring House Corporation Center; Box 457; 321 Norristown Road; Spring House; PA; 19477; US Patent Application Number: 20020035099 Date filed: October 15, 2001 Abstract: This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds that are antagonists of the progesterone receptor having the general structure: 1wherein: R.sub.1, and R.sub.2 are chosen independently from each other from H, OH; OAc; alkylaryl; alkylheteroaryl; 1propynyl; 3-propynyl; and optionally substituted alkyl, O(alkyl); aryl; or heteroaryl groups; or R.sub.1 and R.sub.2 are joined to form a ring comprising -CH.sub.2(CH.sub.2).sub.nCH.sub.2-where n=0-5; --CH.sub.2CH.sub.2CMe.sub.2CH.sub.2CH.sub.2--; --O(CH.sub.2).sub.mCH.sub.2-where m=1-4; O(CH.sub.2).sub.pO-- where p=1-4; --CH.sub.2CH.sub.2OCH.sub.2CH.sub.2--; -CH.sub.2CH.sub.2N(H or alkyl)CH.sub.2CH.sub.2--;or R.sub.1 and R.sub.2 together comprise a double bond to CMe.sub.2; C(cycloalkyl), O, or C(cycloether);R.sub.3 is H, OH, NH.sub.2, COR.sup.A; or optionally substituted alkenyl or alkynyl groups;R.sup.A=H or optionally substituted alkyl, alkoxy, or aminoalkyl groups;R.sub.4=H, halo, CN, NH.sub.2, or optionally substituted alkyl, alkoxy, or aminoalkyl;R.sub.5 is selected from optionally substituted benzene ring; a five or six membered heterocyclic ring; a 4 or 7-substituted indole or a substituted benzothiophene; or pharmaceutically acceptable salt thereof. These methods of treatment may be used for contraception or for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or mininization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake. Excerpt(s): This application is a divisional of U.S. patent application Ser. No. 09/552,631, filed Apr. 19, 2000, which claims the benefit of the priority of U.S. patent application Ser. No. 60/183,057, filed May 4, 1999, now abandoned. This invention relates to regimens of administering compounds, which are antagonists of the progesterone receptor in combination with a progestin, an estrogen, or both. Intracellular receptors (IR) form a class of structurally related gene regulators known as "ligand dependent transcription factors" (R. M. Evans, Science, 240, 889, 1988). The steroid receptor family is a subset of the IR family, including progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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CONTROL OF SELECTIVE ESTROGEN RECEPTOR MODULATORS Inventor(s): HODGEN, GARY D.; (VIRGINIA BEACH, VA) Correspondence: Dickstein Shapiro Morin & Oshinsky Llp; 1177 Avenue OF The Americas; 41st Floor; New York; NY; 10036-2714; US Patent Application Number: 20030181431 Date filed: May 18, 1999 Abstract: The treatment of an estrogen sensitive condition by the administration of a selective estrogen receptor modulator is improved by additionally administering a progestationally active compound to the recipient. The additional agent can express both progestational and androgenic activity or an androgenically active material can be employed, if desired. Additionally, clomiphene in an array of isomeric ratios (EN:ZU) can be used alone for prevention of osteoporosis, maintenance of a healthful blood lipid profile, and prevention of breast tumors, or to sustain amenorrhea. Excerpt(s): This is a continuation-in-part of application Ser. No. 08/888,183, filed Jul. 3, 1997. The use of estrogens in the course of treatment of a variety of conditions is well known. For example, the most prevalent form of oral contraception is the so-called combined oral contraceptive preparation, a pill that combines both estrogen and a progestin. Apparently, the progestin acts foremostly to block gonadotropin release while the estrogen component primarily provides endometrial control to diminish breakthrough bleeding. Another well-known use is long term estrogen replacement therapy which is common for post-menopausal and other estrogen deficient women. Other estrogen dependent conditions include endometriosis, uterine fibroid tumors (leiomyomata), pre-menstrual syndrome, dysfunctional uterine bleeding, breast tumors (benign and malignant) and the like. Despite their value, estrogen treatments are also associated with undesirable side effects. For example, estrogen therapy has been associated with an increased incidence of endometrial cancer, especially due to the continual "unopposed" estrogen-induced proliferation of the endometrium. Other side effects include uterine bleeding and cyclotherapeutic withdrawal menstrual bleeding during a time in their lives when many women welcome cessation of menstrual bleeding as a normal occurrence in menopause. Estrogen therapy has also been implicated in the development of a variety of disorders including gallbladder disease, hypertension, abnormal glucose tolerance, hypercoagulable states and breast cancer, although some of these observations are antidotal in nature and have not been confirmed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for creating intrauterine adhesions Inventor(s): Duchon, Douglas J.; (Chanhassen, MN), Presthus, James; (Edina, MN) Correspondence: Oppenheimer Wolff & Donnelly Llp; 840 Newport Center Drive; Suite 700; Newport Beach; CA; 92660; US Patent Application Number: 20020010457 Date filed: April 24, 2001 Abstract: An apparatus and method of use or treatment are disclosed for creating intrauterine adhesions resulting in amenorrhea. In particular, the apparatus relates to an easily deployed intrauterine implant that readily and consistently reduces or eliminates

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abnormal intrauterine bleeding. In addition, the apparatus is also used as a uterine marker device for visualizing endometrial tissue thickness and potential changes. The method of the present invention serves as a supplement to or a replacement for conventional hysterectomy or ablation/resection procedures used to treat menorrhagia. Excerpt(s): The present application claims priority of U.S. Provisional Application Ser. No. 60/256,529, filed Dec. 18, 2000, and U.S. Provisional Application Ser. No. 60/199,736, filed Apr. 25, 2000, whose contents are fully incorporated herein by reference. Menstrual bleeding is a part of normal life for women. The onset of menstruation, termed menarche, usually occurs at the age of 12 or 13. The length of a woman's monthly cycle may be irregular during the first one to two years. Once the menstrual cycle stabilizes, a normal cycle may range from 20 to 40 days, with 28 days commonly being an average. Age, weight, athletic activity and alcohol consumption are several factors that affect menstrual cycles. For example, younger women (under the age of 21) and older women (over the age of 49) tend to have longer cycle times, generally averaging 31 days and over. Similarly, women who are very thin or athletic also have longer cycles. In contrast, women who consume alcohol on a regular basis tend to have shorter cycle times. Nearly all women, at some time during their reproductive life, experience some type of menstrual disorder. These disorders range from mild to severe, often resulting in numerous lost work hours and the disruption of personal/family life each month. In general, physical symptoms such as bloating, breast tenderness, severe cramping (dysmenorrhea) and slight, temporary weight gain frequently occur during most menstrual cycles. In addition to physical symptoms, emotional hypersensitivity is also very common. Women report a wide range of emotional symptoms, including depression, anxiety, anger, tension and irritability. These symptoms are worse a week or so before a woman's menstrual period, generally resolving afterward. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel topical oestroprogestational compositions with a systemic effect Inventor(s): Gray, Georges; (Monoco, MC), Paris, Jacques `; (Nice, FR), Thomas, JeanLouis; (Charenton-Le-Pont, FR), Villet, Bertrand; (Antibes, FR) Correspondence: Muserlian And Lucas And Mercanti, Llp; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030181430 Date filed: June 26, 2002 Abstract: The present invention relates to the field of therapeutic chemistry and more especially to the realization of new galenic forms intended to be applied on the skin.More particularly it relates to a topical hormonal composition with a systemic effect for the hormonal treatment of the perimenopause and of the menopause as well as for the treatment of the ovarian hormonal deficiencies in women with amenorrhea, characterized in that it comprises, as active ingredients, a progestogen derived from 19nor progesterone and estradiol or one of its derivatives, a vehicle which allows the systemic passage of said active ingredients, chosen from the group constituted by a solubilizing agent, an absorption promoting agent, a film-forming agent, a gelling agent and their mixtures, in combination or in a mixture with suitable excipients for the realization of a gelled and/or film-forming pharmaceutical form. Excerpt(s): The present invention relates to the field of therapeutic chemistry and more especially to the realization of new galenic forms intended to be applied on the skin. A

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more particular subject of the present invention is cutaneous topical preparations the active ingredients of which are a synthetic progestogen and a natural or synthetic estrogen and the penetrating power of which makes it possible to obtain a systemic hormonal effect. The invention relates more specifically to a topical estrogenprogestogen composition with a systemic effect for the hormonal treatment of the perimenopause and of the menopause as well as for the treatment of ovarian hormonal deficiencies in women with amenorrhea. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Progestin therapy for maintaining amenorrhea Inventor(s): Bologna, William J.; (Paris, FR), deZiegler, Dominique; (Paris, FR), Levine, Howard L.; (Oceanside, NY) Correspondence: Lyon & Lyon Llp; Suite 4700; 633 West Fifth Street; Los Angeles; CA; 90071-2066; US Patent Application Number: 20010031747 Date filed: April 3, 2001 Abstract: The present invention teaches that daily, cyclical vaginal delivery of progestin may be used to provide regular, predictable withdrawal bleeding during hormone replacement therapy. The present invention also teaches that constant administration of progestin in a water-insoluble, water-swellable cross-linked polycarboxylic acid polymer may be used to maintain amenorrhea. Either regimen is accompanied by a significant decrease in adverse side effects. Excerpt(s): This invention relates to a method of administering progestin therapy in a manner that promotes controlled bleeding, rather than the irregular and unpredictable bleeding that normally accompanies progestin administration. Progesterone is a naturally occurring steroid which is the main steroid secreted by women during their reproductive years. This steroid has been studied extensively and has been found to be a major precursor in the biosynthesis of most other steroids, particularly glucocorticoids, androgens and estrogens. Progesterone also stimulates the growth of the uterus and a number of specific changes in the endometrium and myometrium. It is essential for the development of decidual tissue and the differentiation of luminal and glandular epithelial tissue. Progesterone also plays several roles in gestation, including breast enlargement, inhibition of uterine contractility, maintenance of gestation, immunological protection of the embryo, and inhibition of prostaglandin synthesis. Progestins include the natural progestin, progesterone, as well as the synthetic progestins, such as medroxyprogesterone acetate (MPA). Progestins have been used pharmaceutically in the treatment of a number of clinical disorders such as luteal phase deficiency, dysfunctional uterine bleeding, endometriosis, endometrial carcinoma, benign breast disease, pre-eclampsia, and assisting in vitro fertilization, preventing early abortion and reducing the occurrence of endometrial hyperplasia in estrogen replacement therapy (ERT). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Thienopyridine compounds, their production and use Inventor(s): Choh, Nobuo; (Ibaraki, JP), Furuya, Shuichi; (Ibaraki, JP), Imada, Takashi; (Ibaraki, JP), Suzuki, Nobuhiro; (Ibaraki, JP) Correspondence: Takeda Pharmaceuticals America, Inc; Intellectual Property Department; 475 Half Day Road; Suite 500; Lincolnshire; IL; 60069; US Patent Application Number: 20010001104 Date filed: December 14, 2000 Abstract: The compound of the present invention possesses excellent gonadotropinreleasing hormone antagonizing activity, and is useful for preventing or treating sex hormone-dependent diseases, e.g., sex hormone-dependent cancers (e.g., prostatic cancer, uterine cancer, breast cancer, pituitary tumor), prostatic hypertrophy, hysteromyoma, endometriosis, precocious puberty, amenorrhea syndrome, multilocular ovary syndrome, pimples etc, or as a pregnancy regulator (e.g., contraceptive), infertility remedy or menstruation regulator. Excerpt(s): 1. The present invention relates to thieno[2,3-b]pyridine derivatives exhibiting gonadotropin releasing hormone (GnRH) antagonizing activity, their production and use. 2. The secretion of hypophysial anterior lobe hormone is regulated by the peripheral hormone secreted by each target organ and the secretion-promoting or secretion-suppressing hormone secreted by the hypothalamus, which is the center superior to the hypophysial anterior lobe, and this group of hormones hereinafter generically referred to as hypothalamic hormone in this specification. To date, nine hypothalamic hormones have been identified, for example, thyroid-stimulating hormone-releasing hormone (TRH), and gonadotropin releasing hormone [GnRH, also known as luteinizing hormone releasing hormone (LH-RH)], etc. It is conjectured that these hypothalamic hormones exhibit their hormone actions etc. via receptors assumed to be present in the hypophysial anterior lobe, and analyses of receptor genes specific to these hormones, including humans, are ongoing. Antagonists or agonists that act specifically and selectively on these receptors would therefore regulate the action of hypothalamic hormones and hence regulate the secretion of hypophysial anterior lobe hormone. As a result, such antagonists or agonists are expected to prevent or treat diseases depending on these hypophysial anterior lobe hormone. 3. Known compounds possessing GnRH-antagonizing activity include GnRH-derived linear peptides (U.S. Pat. No. 5,140,009 and U.S. Pat. No. 5,171,835), a cyclic hexapeptide derivative (JP-A-61191698), a bicyclic peptide derivative [Journal of Medicinal Chemistry, Vol. 36, pp. 32653273 (1993)], and so forth. Non-peptide compounds possessing GnRH-antagonizing activity include compounds described in WO 95/28405, WO 97/14697, WO 97/14682, WO 97/41126 and so forth. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Ultra low dose oral contraceptives with sustained efficacy and induced amenorrhea Inventor(s): Anderson, Freedolph D.; (Virginia Beach, VA), Hodgen, Gary D.; (Virginia Beach, VA), Williams, Robert F.; (Norfolk, VA) Correspondence: Ostrolenk Faber Gerb & Soffen; 1180 Avenue OF The Americas; New York; NY; 100368403 Patent Application Number: 20030018018 Date filed: July 10, 2001

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Abstract: A method of female contraception involves administering a combination of estrogen and progestin continuously for more than a year in which the daily amounts of estrogen and progestin are equivalent to about 5-35 mcg of ethinyl estradiol and about 0.025 to 10 mg of norethindrone acetate, respectively. The advantages include lack of menstrual bleeding, less patient anemia, less total exposure to medication when compared to a 35 microgram (low dose) containing oral contraceptive, reduced risk of endometrial cancer, higher compliance rates and more lifestyle convenience for patients who desire less uterine bleeding each year or longer. Excerpt(s): The ovarian/menstrual cycle is a complex event characterized by an estrogen rich follicular phase and, after ovulation, a progesterone rich luteal phase. Each has a duration of approximately 14 days resulting in an intermenstrual interval of about 28 days. The endometrial tissue responds to the changes in hormonal milieu. The onset of menstruation is the beginning of a new menstrual cycle and is counted as day 1. During a span of about 5 to 7 days, the superficial layers of the endometrium, which grew and developed during the antecedent ovarian/menstrual cycle, are sloughed because demise of the extant corpus luteum in the non-fertile menstrual cycle is associated with a loss of progesterone secretion. Ovarian follicular maturation occurs progressively resulting in a rise in the circulating levels of estrogen, which in turn leads to new endometrial proliferation. The dominant ovarian follicle undergoes ovulation near mid-cycle, generally between menstrual cycle days 12 to 16 and is converted from a predominantly estrogen source to a predominantly progesterone source (the corpus luteum). The increasing level of progesterone in the blood converts the proliferative endometrium to a secretory phase in which the tissue proliferation has promptly abated, leading to the formation of endometrial glands or organs. When the ovulated oocyte is viably fertilized and continues its progressive embryonic cleavage, the secretory endometrium and the conceptus can interact to bring about implantation (nidation), beginning about 6 to 8 days after fertilization. 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 amenorrhea, 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 “amenorrhea” (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 amenorrhea. You can also use this procedure to view pending patent applications concerning amenorrhea. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON AMENORRHEA Overview This chapter provides bibliographic book references relating to amenorrhea. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on amenorrhea 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 “amenorrhea” (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 amenorrhea: •

Taking the first steps: The lactational amenorrhea method: A decade of experience Source: Washington, DC: Institute for Reproductive Health, Georgetown University. 1997. 114 pp. Contact: Available from Georgetown University Medical Center, Institute for Reproductive Health, 3PHC, 3800 Reservoir Road , Washington, DC 20007. Telephone: (202) 687-1392 / fax: (202) 687- 6846 / e-mail: [email protected]. Summary: This report examines in depth the Lactational Amenorrhea Method (LAM) that is designed to support and sustain breastfeeding and child spacing. Topics include the background of the method, launching the LAM program, conference proceedings, and the resultant general consensus and common ground.

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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 “amenorrhea” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “amenorrhea” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “amenorrhea” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Break in Your Cycle : The Medical and Emotional Causes and Effects of Amenorrhea by Theresa Francis-Cheung (Author); ISBN: 0471346632; http://www.amazon.com/exec/obidos/ASIN/0471346632/icongroupinterna

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Clinical Problems: Amenorrhea II: Prg 3; ISBN: 0683162039; http://www.amazon.com/exec/obidos/ASIN/0683162039/icongroupinterna

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Secondary amenorrhoea, self-induced weight reduction and anorexia nervosa by Hans Fries; ISBN: 8716016874; http://www.amazon.com/exec/obidos/ASIN/8716016874/icongroupinterna

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The Athletic Woman's Survival Guide: How to Win the Battle Against Eating Disorders, Amenorrhea, and Osteoporosis by Carol L. Otis, Roger Goldingay; ISBN: 0736001212; http://www.amazon.com/exec/obidos/ASIN/0736001212/icongroupinterna

Chapters on Amenorrhea In order to find chapters that specifically relate to amenorrhea, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and amenorrhea 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 “amenorrhea” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on amenorrhea: •

Women and Exercise Source: in Devlin, J.T. and Schneider, S.H., eds. Handbook of Exercise in Diabetes. Alexandria, VA: American Diabetes Association. 2002. p.511-531. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $69.95 plus shipping and handling. ISBN: 1580400191. Summary: This chapter on women and exercise is from a book that provides a practical, comprehensive guide to diabetes and exercise for health care professionals involved in patient care. The authors focus on three areas: exercise and pregnancy, amenorrhea (lack of a menstrual period) and exercise, and osteoporosis and exercise. Exercise may not be effective for the pregestational woman with type 1 diabetes who is planning a

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pregnancy or is currently pregnant. Exercise in the form of arm ergometry has been documented to be safe for a sedentary, unfit pregnant woman and may be a helpful adjunctive therapy to medical nutritional therapy for a woman with gestational diabetes (a type of diabetes that occurs during pregnancy). After childbirth, if glucose control is maintained, the woman with diabetes should be able to return to an exercise program similar to that of a woman without diabetes. The adolescent girl with diabetes who is amenorrheic needs intensive therapy to ensure that she does not develop accelerated retinopathy (eye disease) when glucose control is achieved. If amenorrhea persists beyond the age of 16, treatment with estrogen therapy to protect the bones is advised. Women with diabetes should be offered a weight bearing exercise program along with hormonal replacement therapy when they reach menopause. In addition, smoking cessation programs are recommended to improve bone mass status. Insulin dosing for the exercising menopausal woman who is taking hormonal replacement therapy is complicated; thus, a team that is expert in insulin therapy is needed as part of the exercise program. 3 figures. 2 tables. 59 references.

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CHAPTER 8. PERIODICALS AND NEWS ON AMENORRHEA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover amenorrhea.

News Services and Press Releases One of the simplest ways of tracking press releases on amenorrhea 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 “amenorrhea” (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 amenorrhea. 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 “amenorrhea” (or synonyms). The following was recently listed in this archive for amenorrhea: •

Hormone therapy fails to reverse bone loss in dancers with amenorrhea Source: Reuters Industry Breifing Date: August 18, 2003

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Supplemental calorie intake may ameliorate exercised-induced amenorrhea Source: Reuters Medical News Date: December 12, 2001

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Female athletes at risk for amenorrhea Source: Reuters Health eLine Date: October 18, 2000

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Copper IUD restores menses in women with secondary amenorrhea Source: Reuters Medical News Date: January 27, 2000

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Transvaginal progesterone gel Crinone effective for secondary amenorrhea Source: Reuters Medical News Date: February 10, 1999

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Leptin low in women with hypothalamic amenorrhea Source: Reuters Medical News Date: July 13, 1998

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Education About Lactational Amenorrhea: Useful Addition To Postpartum Care Source: Reuters Medical News Date: April 21, 1998

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Lactational Amenorrhea 99% Effective As Birth Control In Subset Of Women Source: Reuters Medical News Date: October 08, 1997

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Leuprolide Induces Amenorrhea Prior To Bone Marrow Transplantation Source: Reuters Medical News Date: September 26, 1997

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Crinone Receives FDA Approval For Treatment Of Secondary Amenorrhea Source: Reuters Medical News Date: August 04, 1997

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Abnormal Regulation Of Leptin Linked To Anorexia Nervosa And Amenorrhea Source: Reuters Medical News Date: June 30, 1997 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. 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.

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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 “amenorrhea” (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 “amenorrhea” (or synonyms). If you know the name of a company that is relevant to amenorrhea, 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 “amenorrhea” (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 “amenorrhea” (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 amenorrhea: •

The Female Triad: Are You at Risk? Source: Weight Control Digest. 7(4):645-646; July/Aug 1997. Contact: Weight Control Digest, 1555 W. Mockingbird Lane, Suite 203, Dallas, TX 75235. (800) 736-7323. Summary: This article discusses what the author terms the 'Female Athlete Triad' or the cluster of eating disorders, amenorrhea, and bone loss. Steen says that female athletes, especially in certain 'appearance' sports such as gymnastics, ballet, and figure skating are at risk for developing this triad, due to the emphasis on physical appearance in these sports. Steen suggests such interventions as increased caloric intake, decreased physical

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activity, and, in extreme cases, hormone therapy. However, she says that lifestyle interventions are preferable. •

Menstrual Cycle Dysfunction in Adolescent Athletes: What Parents Should Know Source: Fit Society Page. p. 7. April-June 2001. Contact: American College of Sports Medicine. PO Box 1440, Indianapolis, IN 462061440. Summary: This article provides an overview of menstrual-cycle dysfunction in female adolescent athletes. Girls with heavy training schedules and/or those who are undernourished are most likely to have menstrual irregularities. Girls who experience delayed onset of menstruation, amenorrhea (an absence of menses for 3 months or longer), or irregular menstrual cycles must consider the possibility of an eating disorder and undernourishment. Bulimia and anorexia are the most common eating disorders among female athletes. Parents should be sensitive to the signs of eating disorders and talk with their daughters about healthy eating habits and body image. The article recommends consulting physicians if the possibility of an eating disorder or persistent physical symptoms exist.

•

Weight Management Update Source: Fit Society Page. p. 7-8. Spring 2002. Contact: American College of Sports Medicine. P.O. Box 1440, Indianapolis, IN 462061440. www.acsm.org. Summary: This article reviews recent research in the area of weight management. According to a report from the Women's Health Initiative, challenges in maintaining a low-fat diet arise when eating out, traveling, and attending celebrations and holiday gatherings. Strategies for maintaining healthy eating during these occasions are provided. The author reviews research conducted by investigators at Ball State University in Muncie, Indiana, who studied 59 overweight and obese women following three different 1200-calorie diets for 12 weeks. Women who completed the study lost an average of 9 pounds, regardless of diet type: high protein, high fat; high carbohydrate, low fat; or standard proportions of protein, fat, and carbohydrates. The article also details the latest research on the relationship between amenorrhea (lack of menstruation), thinness, bone health, and exercise. Online weight management information is also reviewed, and the high drop-out rates of participants in these Internet- based programs is noted.

•

Preventing Osteoporosis : Why Milk Matters Now for Female Teens Source: NIH News and Features. 65-66. Summary: This newsletter article for the general public discusses the importance of a nutritionally balanced diet during childhood and adolescence in preventing the onset of damaging adult illness such as osteoporosis. Nutritional imbalances during adolescence results in this bone-crippling disease because the occurrence of osteoporosis is influenced by bone mass attained during the first three decades of life and the bone lost after a menopause. The article presents the recommended daily allowance of calcium for adolescent females, and it reports on nutrition research on factors affecting acquisition of peak bone mass in female adolescents and on a study of calcium requirements during adolescent pregnancies. In addition, the article discusses the impact of osteopenia,

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amenorrhea, and disordered eating on the adolescent female athlete, and it considers the public health implications of the declining calcium intake in female adolescents.

Academic Periodicals covering Amenorrhea Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to amenorrhea. In addition to these sources, you can search for articles covering amenorrhea 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.” 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.”

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CHAPTER 9. 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 amenorrhea. 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 amenorrhea. 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

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to amenorrhea: Bromocriptine •

Systemic - U.S. Brands: Parlodel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202094.html

Danazol •

Systemic - U.S. Brands: Danocrine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202180.html

Estrogens and Progestins Oral Contraceptives •

Systemic - U.S. Brands: Alesse; Brevicon; Demulen 1/35; Demulen 1/50; Desogen; Estrostep; Estrostep Fe; Genora 0.5/35; Genora 1/35; Genora 1/50; Intercon 0.5/35; Intercon 1/35; Intercon 1/50; Jenest; Levlen; Levlite; Levora 0.15/30; Lo/Ovral; Loestrin 1.5/30; Loestrin 1/20 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202228.html

Gonadorelin •

Systemic - U.S. Brands: Factrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202265.html

Progestins for Noncontraceptive Use •

Systemic - U.S. Brands: Amen; Aygestin; Crinone; Curretab; Cycrin; DepoProvera; Gesterol 50; Gesterol LA 250; Hy/Gestrone; Hylutin; Megace; Prodrox; Prometrium; Pro-Span; Provera http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202758.html

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

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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 amenorrhea 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 “amenorrhea” (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 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 amenorrhea: •

Gonadorelin acetate (trade name: Lutrepulse) http://www.rarediseases.org/nord/search/nodd_full?code=723

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.

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APPENDICES

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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 Institute8: •

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/

8

These publications are typically written by one or more of the various NIH Institutes.

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•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.9 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:10 •

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

9

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). 10 See http://www.nlm.nih.gov/databases/databases.html.

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•

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 NLM Gateway11 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.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “amenorrhea” (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. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 11686 1461 36 20 108 13311

HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 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.15 Simply search by “amenorrhea” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

11

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

12

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). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14 15

The HSTAT URL is http://hstat.nlm.nih.gov/.

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.

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Coffee Break: Tutorials for Biologists16 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.17 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.18 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/.

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 Amenorrhea In the following section, we will discuss databases and references which relate to the Genome Project and amenorrhea. 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).19 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. 16 Adapted 17

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. 18 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. 19 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.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “amenorrhea” (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 amenorrhea: •

Amenorrhea-Galactorrhea Syndrome Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104600 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: •

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

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•

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

•

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

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “amenorrhea” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database20 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. The Genome Database21 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 “amenorrhea” (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).

20

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 21 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 amenorrhea 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 amenorrhea. 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 amenorrhea. 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 “amenorrhea”:

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Other guides Adrenal Gland Disorders http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html Endocrine Diseases http://www.nlm.nih.gov/medlineplus/endocrinediseases.html Infertility http://www.nlm.nih.gov/medlineplus/infertility.html Menstruation and Premenstrual Syndrome http://www.nlm.nih.gov/medlineplus/menstruationandpremenstrualsyndrome.ht l Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Ovarian Cysts http://www.nlm.nih.gov/medlineplus/ovariancysts.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.html

Within the health topic page dedicated to amenorrhea, the following was listed: •

General/Overviews Menstruation and the Menstrual Cycle Source: National Women's Health Information Center http://www.4woman.org/faq/menstru.htm Premenstrual Syndrome Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00134

•

Diagnosis/Symptoms Estrogen Tests Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/estrogen/test.html FSH (Follicle-Stimulating Hormone) Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/fsh/test.html

•

Treatment Dilation and Curettage http://www.nlm.nih.gov/medlineplus/tutorials/dilationandcurettageloader.html PMS: What You Can Do to Ease Your Symptoms Source: American Academy of Family Physicians http://familydoctor.org/141.xml

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Specific Conditions/Aspects Amenorrhea: When Menstruation Goes Away Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00224 Do I Have Premature Ovarian Failure? Source: National Institute of Child Health and Human Development http://www.nichd.nih.gov/publications/pubs/pof/index.htm Dysmenorrhea Source: University of Utah, Health Sciences Center http://www.med.utah.edu/healthinfo/adult/gynonc/dysmen.htm Hormonal Causes of Ovulatory Disorders Source: Resolve http://www.resolve.org/main/national/treatment/diagnosis/thyroid.jsp?name=t reatment&tag=diagnosis Is PMDD Real? Source: American Psychological Association http://www.apa.org/monitor/oct02/pmdd.html Menorrhagia Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00394 Menorrhagia Source: University of Utah, Health Sciences Center http://www.med.utah.edu/healthinfo/adult/women/menor.htm Menstrual Hygiene Products Source: American College of Obstetricians and Gynecologists http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZV9LN187C &sub_cat=328 Mittelschmerz Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00507 Premenstrual Dysphoric Disorder: A Guide for Patients and Families http://www.psychguides.com/DinW%2520PMDD.pdf Tampon Safety: TSS Now Rare, but Women Still Should Take Care Source: Food and Drug Administration http://www.fda.gov/fdac/features/2000/200_tss.html Vaginal Bleeding Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HO00159

•

Children All about Menstruation Source: Nemours Foundation http://kidshealth.org/kid/grow/body_stuff/menstruation.html

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Period Talk: Preparing Your Preteen for Menstruation Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=FL00040 When Will I Get My Period? Source: Nemours Foundation http://kidshealth.org/kid/grow/body_stuff/when_period.html •

Latest News Antidepressant Relieves PMS Source: 02/27/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16306 .html

•

Organizations American College of Obstetricians and Gynecologists http://www.acog.org/ National Institute of Child Health and Human Development http://www.nichd.nih.gov/ National Women's Health Information Center Source: Dept. of Health and Human Services http://www.4woman.gov/

•

Pictures/Diagrams Atlas of the Body: Female Reproductive Organs Source: American Medical Association http://www.medem.com/MedLb/article_detaillb.cfm?article_ID=ZZZ8QKJ56JC&s ub_cat=2

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Prevention/Screening Menstrual Cycle Problems: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/538.xml

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Research Irregular Periods in Young Women Could Be Warning Sign for Later Osteoporosis Source: National Institute of Child Health and Human Development http://www.nih.gov/news/pr/may2002/nichd-29.htm

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Teenagers All about Menstruation Source: Nemours Foundation http://kidshealth.org/teen/sexual_health/girls/menstruation.html

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Coping with Common Period Problems Source: Nemours Foundation http://kidshealth.org/teen/sexual_health/girls/menstrual_problems.html Deal with Feminine Hygiene Source: Nemours Foundation http://kidshealth.org/teen/sexual_health/girls/feminine_hygiene.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 amenorrhea. 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: •

Birth control: Your choices Source: [Austin, TX]: Texas Department of Health. 1996. 16 pp. Contact: Available from Texas Department of Health, 1100 West 49th Street, Austin, TX 78756. Telephone: (512) 458-7658 or (800) 434-4453 / fax: (512) 458-7713. Summary: This educational booklet describes various birth control techniques. The booklet describes how each technique works and how it is used; indicates possible problems, benefits, and disadvantages; and reviews how well the technique works. It covers condoms; female condoms; spermicidal foams, jellies, creams, and suppositories, and contraceptive films; diaphragms, intrauterine devices, Norplant, depo-provera, the pill, the lactational amenorrhea method, sterilization, natural family planning, and abstinence. 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 amenorrhea. 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 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.

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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: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

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

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

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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

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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 amenorrhea. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with amenorrhea. 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 amenorrhea. 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/. Simply type in “amenorrhea” (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

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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 “amenorrhea”. 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 “amenorrhea” (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 “amenorrhea” (or a synonym) into the search box, and click “Submit Query.”

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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.22

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

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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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)23: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

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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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

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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

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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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

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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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

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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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/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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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/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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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 amenorrhea: •

Basic Guidelines for Amenorrhea Amenorrhea - primary Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001218.htm Stein-Leventhal syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000369.htm

•

Signs & Symptoms for Amenorrhea Amenorrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003149.htm Extreme obesity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003102.htm Galactorrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003154.htm

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Diagnostics and Tests for Amenorrhea 17-ketosteroids Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003460.htm Chromosome analysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003935.htm FSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003710.htm Head CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm Head MRI scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003791.htm Laparoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003918.htm LH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003708.htm Prolactin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003718.htm T3 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003687.htm T4 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003517.htm TSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm Urine chemistry Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003342.htm

•

Background Topics for Amenorrhea Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Heart disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000147.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm

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Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Weight reduction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001940.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

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AMENORRHEA 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 Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablation: The removal of an organ by surgery. [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] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Adenocarcinomas: A malignant tumor of the epithelial cells of a gland which typically metastasizes by way of the lymphatics. [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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [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] 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 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

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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] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] 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] 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] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] 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] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] 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] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alopecia: Absence of hair from areas where it is normally present. [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] Amenorrhea: Absence of menstruation. [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 (-

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COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] 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] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] 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] Animal Husbandry: The science of breeding, feeding, and care of domestic animals; includes housing and nutrition. [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]

Anosmia: Absence of the sense of smell; called also anosphrasia and olfactory anaesthesia. [EU]

Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH]

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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]

Anterior Cruciate Ligament: A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] 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]

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 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] Antidiarrheals: Miscellaneous agents found useful in the symptomatic treatment of diarrhea. They have no effect on the agent(s) that cause diarrhea, but merely alleviate the condition. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] 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]

Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the

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movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aqueous: Having to do with water. [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] Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [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

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variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autonomic: Self-controlling; functionally independent. [EU] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [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] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Behavioral Medicine: The interdisciplinary field concerned with the development and integration of behavioral and biomedical science, knowledge, and techniques relevant to health and illness and the application of this knowledge and these techniques to prevention, diagnosis, treatment, and rehabilitation. [NIH] Benign: Not cancerous; 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] 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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Psychiatry: An interdisciplinary science concerned with studies of the biological bases of behavior - biochemical, genetic, physiological, and neurological - and applying these to the understanding and treatment of mental illness. [NIH]

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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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a 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] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [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] 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 Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [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 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,

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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 Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [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] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [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] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA

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from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [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] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] 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] 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] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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 series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU]

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Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] 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 Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [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 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

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] Chemotherapy: Treatment with anticancer drugs. [NIH]

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Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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 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 transplantation to replace the work of the kidneys. [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] 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] 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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [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] 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] 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

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knowledge. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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. 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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [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]

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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] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [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: 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] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [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] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] 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] 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]

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 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

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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 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] 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] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [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] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH]

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Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyproheptadine: A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytotoxic: Cell-killing. [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] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [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] 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] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and

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immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [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] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] 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] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] 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]

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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] 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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]

symptoms

resulting

from

an

absent

or

Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]

Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dysgenesis: Defective development. [EU] Dysgerminoma: A malignant ovarian neoplasm, thought to be derived from primordial germ cells of the sexually undifferentiated embryonic gonad. It is the counterpart of the classical seminoma of the testis, to which it is both grossly and histologically identical. Dysgerminomas comprise 16% of all germ cell tumors but are rare before the age of 10, although nearly 50% occur before the age of 20. They are generally considered of low-grade malignancy but may spread if the tumor extends through its capsule and involves lymph nodes or blood vessels. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1646 [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] 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

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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] Emboli: 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] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [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] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH]

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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] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [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] 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] Ergometer: An instrument for measuring the force of muscular contraction. [NIH] Ergometry: Any method of measuring the amount of work done by an organism, usually during exertion. Ergometry also includes measures of power. Some instruments used in these determinations include the hand crank and the bicycle ergometer. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] 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] 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] 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]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH]

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Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [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] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] 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] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [NIH] 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] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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,

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usually as a consequence of inflammation or other injury. [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] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] 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] FSH: A gonadotropic hormone found in the pituitary tissues of mammals. It regulates the metabolic activity of ovarian granulosa cells and testicular Sertoli cells, induces maturation of Graafian follicles in the ovary, and promotes the development of the germinal cells in the testis. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastrectomy: An operation to remove all or part of the stomach. [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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical

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preparations, and in the manufacturing of capsules and suppositories. [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]

Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [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] Gigantism: The condition of abnormal overgrowth or excessive size of the whole body or any of its parts. [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] 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] 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] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when

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cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulosa Cell Tumor: An ovarian tumor originating in the cells of the primordial membrana granulosa of the graafian follicle. It may be associated with excessive production of estrogen. [NIH] 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] 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] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH]

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Health Surveys: A systematic collection of factual data pertaining to health and disease in a human population within a given geographic area. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [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 of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [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] Hepatotoxic: Toxic to liver cells. [EU] 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] 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]

Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] 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] Hormonal: Pertaining to or of the nature of a hormone. [EU]

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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] Hospital Records: Compilations of data on hospital activities and programs; excludes patient medical records. [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] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] 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] 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] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to

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an increase in the number of cells. [NIH] Hypnotherapy: Sleeping-cure. [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] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamic Hormones: Hormones isolated from the hypothalamus which exercise control over other organs, primarily the pituitary gland. Well-known members include certain pituitary hormone-releasing hormones and pituitary hormone release inhibiting hormones. Vasopressin and oxytocin which are found in the posterior pituitary may also be secreted by the hypothalamus but are not grouped here (pituitary hormones, posterior). [NIH]

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] Hysterectomy: Excision of the uterus. [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 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] 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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] 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] Immunosuppressive: Describes the ability to lower immune system responses. [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] 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

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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] 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] Inertia: Inactivity, inability to move spontaneously. [EU] Infantile: Pertaining to an infant or to infancy. [EU] 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] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] 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] 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] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may

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be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] 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] 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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intrinsic Factor: A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12. Deficiency of intrinsic factor results in pernicious anemia. [NIH]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These

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may be transported in the same (symport) or opposite (antiport) direction. [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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] 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] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [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 intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [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] 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] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] 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] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing

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hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [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] 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]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lipid: Fat. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lisuride: An ergot derivative that acts as an agonist at dopamine D2 receptors, may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors. It has been used in parkinsonism but it may be hepatotoxic. It is commonly used as a research tool. [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] Localized: Cancer which has not metastasized yet. [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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [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] 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).

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[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] 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] Malignant tumor: A tumor capable of metastasizing. [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] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [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 Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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] 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.

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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] 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] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menorrhagia: Excessive menstrual flow. [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 deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [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] 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] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [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] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone,

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predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] 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] 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, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [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] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motility: The ability to move spontaneously. [EU] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [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 relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being

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stretched. [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] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [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] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] 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] 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] 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] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU]

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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] 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] 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] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] 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] 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] 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous 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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nidation: Implantation of the conceptus in the endometrium. [EU] 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] Norethindrone: A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational

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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] 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] 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] 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] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [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] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [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]

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] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] 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 Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent,

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albuminous fluid in which the ovum is suspended. [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] Ovulation Induction: Techniques for the artifical induction of ovulation. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [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]

Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [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] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] 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] 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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU]

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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] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Pergolide: A long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. [NIH]

Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [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] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenyl: Ingredient used in cold and flu remedies. [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] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH]

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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] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary Hormone Release Inhibiting Hormones: Polypeptide hormones produced in the hypothalamus which inhibit the release of pituitary hormones. Used for PHRIH in general or for which there is no specific heading. [NIH] Pituitary Hormone-Releasing Hormones: Hormones released by one structure (e.g., the hypothalamus or the thyroid gland) that effect the secretion of hormones from the pituitary gland. [NIH] Pituitary Hormones: Hormones secreted by the anterior and posterior lobes of the pituitary gland and the pars intermedia, an ill-defined region between the two. Their secretion is regulated by the hypothalamus. [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] 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] 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] 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] 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]

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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] Postpartum Hemorrhage: The presence of abnormal uterine bleeding immediately after labor or childbirth. [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] 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] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] 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 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] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [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] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and

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painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [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] 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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] 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] Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [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] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [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

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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 (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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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] 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] Proximate cause: The abnormal event in a causal chain lying closest to an accidental event. [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]

Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU]

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Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] 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]

Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] 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] 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] 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 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] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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,

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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] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] Rebound effect: The characteristic of a drug to produce reverse effects when either the effect of the drug has passed, or when the patient no longer responds to the drug. [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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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] Reproduction Techniques: Methods pertaining to the generation of new individuals. [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] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [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,

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4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Resting metabolic rate: RMR accounts for 65 to 75 percent of daily energy expenditure and represents the minimum energy needed to maintain all physiological cell functions in the resting state. The principal determinant of RMR is lean body mass (LBM). Obese subjects have a higher RMR in absolute terms than lean individuals, an equivalent RMR when corrected for LBM and per unit surface area, and a lower RMR when expressed per kilogram of body weight. Obese persons require more energy for any given activity because of a larger mass, but they tend to be more sedentary than lean subjects. [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] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [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] 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

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characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] 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] 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] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Seminoma: A type of cancer of the testicles. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] 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] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [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] 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

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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] Sexual Partners: Married or single individuals who share sexual relations. [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] 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] 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]

Smooth Muscle Tumor: A tumor composed of smooth muscle tissue, as opposed to leiomyoma, a tumor derived from smooth muscle. [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] 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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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]

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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] 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] 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] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] 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] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] 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] Stillbirth: The birth of a dead fetus or baby. [NIH] 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] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [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] Stromal: Large, veil-like cell in the bone marrow. [NIH] 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]

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Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] 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] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] 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] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH]

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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] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Theca Cells: The connective tissue cells of the ovarian follicle. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thinness: A state of insufficient flesh on the body usually defined as having a body weight less than skeletal and physical standards. [NIH] 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] 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] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired

Dictionary 189

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 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] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] 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] 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] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [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] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [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] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trivalent: Having a valence of three. [EU] 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] 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

190

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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 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] 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] 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] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] 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] 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [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] Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] 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

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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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Virilism: Development of masculine traits in the female. [NIH] 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] 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] 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] 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] 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] Zygote: The fertilized ovum. [NIH]

193

INDEX 1 17-Ketosteroids, 136, 139 A Abdomen, 139, 145, 146, 167, 168, 175, 176, 186, 188 Abdominal, 28, 37, 139, 168, 175, 176, 178 Abdominal Pain, 37, 139 Ablation, 52, 60, 92, 139 Acetylcholine, 139, 149 Acne, 45, 60, 83, 87, 88, 139, 153 Acne Vulgaris, 45, 60, 83, 87, 88, 139 Adenocarcinomas, 90, 139 Adenoma, 39, 50, 56, 83, 87, 88, 139, 179 Adenosine, 139, 146, 176 Adhesions, 53, 91, 139 Adipocytes, 139, 151, 167 Adjunctive Therapy, 99, 139 Adjuvant, 34, 36, 64, 139, 159 Adolescence, 58, 104, 139 Adrenal Cortex, 139, 140, 152, 157, 163, 179 Adrenal Medulla, 139, 147, 156, 157, 173 Adrenergic, 139, 143, 154, 157, 187 Adverse Effect, 5, 14, 16, 30, 140, 185 Afferent, 13, 140, 167 Affinity, 12, 84, 140, 185 Age of Onset, 140, 146, 190 Aggravation, 84, 140 Agonist, 84, 140, 146, 149, 154, 168, 172, 176, 182, 187 Aldosterone, 140, 170 Alertness, 140, 146 Algorithms, 28, 140, 145 Alkaline, 140, 147 Alkaloid, 140, 146, 149 Allergen, 140, 153, 184 Alopecia, 140, 153 Alternative medicine, 103, 140 Amino Acids, 140 Amphetamines, 141, 149 Anabolic, 8, 141 Anaesthesia, 141, 165 Anal, 14, 141, 159, 168 Analgesics, 7, 141 Analog, 141, 167 Analytes, 122, 141 Anatomical, 11, 13, 141, 143, 156, 164, 184 Androgenic, 8, 60, 91, 141, 173

Androgens, 10, 21, 93, 139, 141, 152, 163 Anemia, 6, 95, 119, 141, 176, 188 Anesthesia, 141, 153 Animal Husbandry, 84, 88, 89, 141 Animal model, 11, 12, 18, 20, 25, 141 Anions, 141, 167, 184 Anomalies, 141, 187 Anorexia, 6, 7, 11, 13, 19, 22, 24, 30, 32, 34, 42, 44, 45, 53, 58, 98, 102, 104, 141 Anorexia Nervosa, 6, 7, 11, 13, 19, 24, 30, 32, 44, 45, 53, 98, 102, 141 Anosmia, 16, 31, 141 Anovulation, 9, 10, 11, 25, 26, 27, 45, 56, 141, 177 Antagonism, 142, 146 Antecedent, 95, 142 Anterior Cruciate Ligament, 7, 142 Antiallergic, 142, 152, 153 Antibacterial, 142, 186 Antibiotic, 142, 186 Antibody, 140, 142, 150, 161, 162, 164, 165, 169, 181, 182, 184, 186 Antidiarrheals, 8, 142 Antiemetic, 142, 143, 170 Antigen, 140, 142, 150, 162, 163, 164, 165, 169, 181, 184 Antihypertensive, 142, 176 Anti-inflammatory, 8, 142, 152, 160 Antineoplastic, 63, 142, 152, 153 Antineoplastic Agents, 63, 142 Antioxidants, 8, 142 Antipruritic, 142, 153 Antipsychotic, 142, 173, 183 Anus, 141, 143, 146, 166 Anxiety, 6, 63, 83, 92, 143 Apathy, 143, 173 Aqueous, 143, 144, 167 Arachidonic Acid, 143, 179 Arcuate Nucleus, 13, 143 Arterial, 143, 148, 151, 163, 180, 187 Arteries, 143, 145, 152, 170, 172, 181 Arterioles, 143, 145 Aseptic, 143, 186 Aspartate, 13, 143 Aspiration, 6, 143 Assay, 26, 143, 181 Asymptomatic, 4, 143 Ataxia, 118, 119, 143, 163, 188

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Atherogenic, 4, 143 Atresia, 35, 143 Atrial, 43, 143, 151, 189 Atrioventricular, 143, 151 Atrium, 143, 151, 189, 191 Atrophy, 49, 118, 143, 168 Atypical, 15, 144, 183 Autonomic, 27, 35, 139, 143, 144, 173 Axillary, 46, 144 B Bacteria, 142, 144, 156, 161, 163, 170, 186, 190 Bactericidal, 144, 157 Barbiturate, 144, 188 Basal Ganglia, 143, 144, 146 Basal Ganglia Diseases, 143, 144 Base, 12, 144, 153, 158, 167, 187 Behavior Therapy, 144 Behavioral Medicine, 28, 144 Benign, 83, 87, 88, 91, 93, 139, 144, 146, 158, 160, 161, 167, 172, 181 Benzene, 90, 144 Bilateral, 58, 144, 177 Bile, 144, 159, 168, 186 Biochemical, 16, 40, 144, 184 Biological Psychiatry, 30, 144 Biological therapy, 145, 161 Biomarkers, 26, 145 Biopsy, 23, 145 Biosynthesis, 21, 93, 143, 145 Biotechnology, 31, 103, 115, 117, 118, 119, 145 Bipolar Disorder, 15, 145 Bladder, 145, 165, 180, 190 Blastocyst, 145, 151, 156, 177 Bloating, 92, 145 Blood Coagulation, 145, 147 Blood Platelets, 145, 184, 188 Blood pressure, 4, 142, 145, 147, 163, 171, 181, 185 Blood vessel, 28, 145, 146, 147, 148, 151, 155, 156, 160, 162, 167, 185, 186, 187, 188, 190 Body Composition, 14, 19, 38, 145 Body Fluids, 145, 185, 190 Body Image, 6, 20, 104, 145 Body Mass Index, 8, 145, 175 Bone Density, 6, 7, 8, 29, 145 Bone Marrow, 44, 102, 144, 145, 146, 157, 161, 164, 171, 186 Bone Marrow Transplantation, 44, 102, 146

Bone scan, 8, 146 Boron, 8, 146 Boron Neutron Capture Therapy, 146 Bowel, 141, 146, 154, 176 Bowel Movement, 146, 154 Brain Neoplasms, 146, 163, 188 Branch, 133, 146, 175, 181, 185, 188 Breeding, 141, 146 Bromocriptine, 60, 108, 146 Buccal, 146, 168 Bulimia, 6, 34, 58, 104, 146 C Caffeine, 8, 146 Calcitonin Gene-Related Peptide, 43, 146 Calcium, 6, 7, 14, 15, 62, 75, 104, 146, 147, 150 Caloric intake, 7, 103, 147 Capsules, 147, 155, 160 Carbohydrate, 104, 147, 152, 160 Carcinogenic, 144, 147, 165, 186 Carcinogens, 147, 149, 174 Carcinoma, 93, 147, 153 Cardiac, 146, 147, 151, 157, 158, 172, 186 Cardiovascular, 6, 8, 10, 20, 43, 147, 184 Cardiovascular disease, 10, 20, 147 Carnitine, 8, 62, 147 Carrier Proteins, 147, 177, 181 Case report, 33, 35, 36, 38, 147, 149 Case series, 147, 149 Catecholamine, 147, 154 Caudal, 147, 154, 164, 178 Causal, 147, 180, 183 Causality, 27, 28, 148 Cause of Death, 28, 148 Cell Aggregation, 148, 174 Cell Division, 118, 144, 148, 161, 177, 179 Cell membrane, 147, 148, 153, 166, 176, 178 Cell Survival, 148, 161 Central Nervous System, 17, 43, 82, 139, 141, 144, 146, 148, 149, 155, 159, 161, 163, 184 Central Nervous System Infections, 148, 161, 163 Cerebellar, 143, 148, 182 Cerebral, 143, 144, 146, 148, 157, 158, 163, 180, 188 Cerebral Infarction, 148, 163 Cerebrospinal, 36, 148, 163, 179 Cerebrospinal fluid, 36, 148, 163, 179 Cerebrovascular, 144, 147, 148, 188 Cerebrum, 148, 189

Dictionary 195

Cervical, 4, 87, 148 Cervix, 83, 88, 148, 182 Chemotherapy, 34, 36, 64, 148 Chlamydia, 29, 149 Cholesterol, 144, 149, 152, 182, 186, 187 Choline, 8, 149 Chromium, 8, 149 Chromosomal, 16, 149, 171 Chromosome, 58, 136, 149, 167 Chronic, 9, 18, 20, 25, 27, 29, 31, 53, 55, 60, 118, 136, 139, 149, 154, 156, 165, 167, 177, 187 Chronic renal, 149, 177 Clinical Medicine, 149, 178 Clinical study, 12, 149, 151 Clinical trial, 9, 77, 78, 115, 149, 151, 155, 171, 180, 182 Clomiphene, 32, 33, 44, 91, 149 Cloning, 20, 145, 149 Coal, 144, 149 Coca, 149 Cocaine, 8, 18, 149 Cofactor, 149, 180 Cognition, 149, 173 Cognitive behavior therapy, 28, 52, 150 Colloidal, 150, 184 Combination Therapy, 150, 157 Complement, 150, 160, 167, 177, 184 Complementary and alternative medicine, 63, 74, 150 Complementary medicine, 63, 150 Complete remission, 5, 150, 182 Complete response, 150 Computational Biology, 115, 117, 150 Conception, 26, 151, 158, 178, 186 Concomitant, 11, 38, 151 Condoms, 125, 151 Cone, 13, 151, 187 Confusion, 151, 173 Connective Tissue, 146, 151, 158, 159, 168, 187, 188 Connective Tissue Cells, 151, 188 Consciousness, 141, 151, 154 Constitutional, 16, 151 Consultation, 30, 151 Consumption, 8, 30, 92, 151, 174, 183 Continuous infusion, 85, 151 Contraception, 12, 13, 14, 33, 36, 38, 39, 47, 50, 54, 90, 91, 95, 151, 168, 173 Contraceptive, 7, 12, 14, 36, 38, 40, 64, 84, 87, 88, 91, 94, 95, 125, 151, 169, 174 Contractility, 93, 151

Contraindications, ii, 151 Controlled clinical trial, 20, 151 Controlled study, 22, 23, 151 Cor, 14, 36, 43, 151, 152, 179 Coronary, 147, 152, 170, 172 Coronary heart disease, 147, 152 Coronary Thrombosis, 152, 170, 172 Corpus, 95, 152, 168, 176, 179, 188 Corpus Luteum, 95, 152, 168, 179 Cortex, 70, 71, 143, 152, 156, 158, 182 Cortical, 63, 152, 158, 184, 188 Corticosteroid, 152, 178 Corticotropin-Releasing Hormone, 36, 43, 152 Cortisol, 10, 19, 43, 56, 152 Craniocerebral Trauma, 144, 152, 161, 163, 188 Creatine, 8, 152 Creatinine, 5, 152 Criterion, 44, 152 Cues, 24, 152 Cultured cells, 21, 152 Curare, 153, 171 Curative, 153, 173, 188 Cutaneous, 93, 153, 168 Cyclic, 9, 32, 85, 86, 87, 88, 89, 90, 94, 146, 153, 180 Cyclophosphamide, 5, 50, 153 Cyproheptadine, 40, 153 Cyproterone, 153, 159 Cytokine, 153, 188 Cytotoxic, 153, 181, 182 D Databases, Bibliographic, 115, 153 Degenerative, 153, 183 Dehydroepiandrosterone, 8, 153 Deletion, 58, 153 Dendrites, 153, 173 Density, 6, 8, 14, 15, 35, 36, 55, 61, 65, 145, 153, 174 Dentate Gyrus, 153, 162 Depolarization, 24, 153 Desensitization, 84, 153 Deuterium, 154, 163 Diabetes Insipidus, 33, 49, 54, 154 Diabetes Mellitus, 12, 154, 160, 162 Diagnostic procedure, 81, 103, 154 Diarrhea, 142, 154 Diastolic, 154, 163 Diencephalon, 154, 164, 188 Digestion, 144, 146, 154, 168, 186 Digestive system, 78, 154

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Dilation, 122, 154, 163 Direct, iii, 11, 18, 107, 149, 154, 182 Disinfectant, 154, 157 Dissociation, 140, 154 Diuresis, 146, 154 Diurnal, 42, 154 Dopamine, 13, 82, 83, 143, 146, 149, 154, 168, 170, 176, 183 Dopamine Agonists, 83, 154 Dorsal, 154, 178 Dosage Forms, 85, 155 Double-blinded, 22, 155 Drug Interactions, 108, 109, 155 Dumping Syndrome, 153, 155 Dwarfism, 54, 155 Dynorphins, 155, 174 Dysgenesis, 46, 155 Dysgerminoma, 53, 155 Dysmenorrhea, 26, 86, 92, 123, 155 Dyspareunia, 86, 155, 157 Dysplasia, 119, 155 Dystrophy, 118, 155 E Eating Disorders, 3, 5, 6, 8, 22, 24, 25, 30, 55, 98, 103, 104, 155 Ectopic, 28, 86, 155 Edema, 155, 166, 178 Efficacy, 5, 10, 12, 28, 47, 54, 60, 64, 94, 155 Ejaculation, 155, 184 Elective, 155 Electrolyte, 6, 87, 140, 152, 155, 171, 178, 185 Electrons, 144, 155, 167, 175, 181, 182 Emboli, 49, 156 Embolization, 49, 156 Embryo, 93, 145, 156, 165, 178, 186 Embryo Transfer, 156, 178 Enamel, 6, 156 Endocrine System, 156, 173 Endometrial, 12, 21, 23, 29, 30, 32, 49, 52, 56, 60, 86, 91, 92, 93, 95, 156 Endometriosis, 83, 84, 86, 87, 88, 90, 91, 93, 94, 156, 168, 173, 174 Endometrium, 23, 30, 90, 91, 93, 95, 156, 170, 173 Endorphins, 156, 174, 179 Endothelial cell, 44, 156 End-stage renal, 149, 156, 177 Energy balance, 11, 24, 156, 167 Enkephalins, 156, 174 Entorhinal Cortex, 156, 162 Environmental Exposure, 26, 157, 174

Environmental Health, 25, 114, 116, 157 Enzymatic, 147, 150, 157, 162 Enzyme, 21, 157, 170, 177, 180, 187, 191 Ependyma, 143, 157, 188 Epinephrine, 139, 154, 157, 173, 190 Epithelial, 93, 139, 157, 171 Epithelial Cells, 139, 157, 171 Ergometer, 157 Ergometry, 99, 157 Ergot, 146, 157, 168 Erythrocytes, 141, 146, 157, 184 Erythropoietin, 8, 157 Esophagus, 143, 154, 157, 186 Essential Tremor, 118, 157 Estradiol, 14, 92, 157 Estrogen receptor, 23, 90, 149, 157 Estrogen Replacement Therapy, 6, 91, 93, 157 Ethanol, 17, 157 Ethinyl Estradiol, 40, 95, 158 Eukaryotic Cells, 158, 165 Evoke, 24, 158, 186 Excipients, 92, 158 Excitability, 24, 158 Excitation, 13, 141, 158 Excitatory, 18, 158 Exogenous, 16, 46, 52, 158, 190 Extrapyramidal, 143, 154, 158 Extremity, 7, 158 F Fallopian Tubes, 158, 182 Family Planning, 66, 115, 125, 158 Fat, 19, 64, 76, 104, 139, 143, 145, 146, 151, 152, 156, 158, 167, 168, 175, 184, 185, 189 Fatty acids, 158, 179 Feeding Behavior, 25, 30, 158 Femoral, 7, 14, 58, 158 Femur, 142, 158 Fertilization in Vitro, 158, 178 Fetal Alcohol Syndrome, 17, 158 Fetus, 157, 158, 177, 179, 186, 190 Fibroid, 91, 158, 167 Fibrosis, 119, 158, 184 Fixation, 159, 184 Flutamide, 45, 60, 159 Fold, 21, 159 Follicles, 16, 21, 159, 165 Follicular Phase, 26, 95, 159 Forearm, 145, 159 FSH, 16, 19, 26, 87, 122, 136, 159, 161, 165 G Gallbladder, 91, 139, 154, 159

Dictionary 197

Gamma Rays, 159, 182 Ganglia, 139, 144, 159, 173 Gas, 159, 163, 173, 190 Gasoline, 144, 159 Gastrectomy, 153, 159 Gastric, 147, 155, 159, 162, 166 Gastrin, 159, 163 Gastrointestinal, 6, 30, 155, 157, 158, 159, 167, 184, 187, 190 Gastrointestinal tract, 157, 158, 159, 167, 184, 190 Gelatin, 159, 187 Gene, 16, 26, 90, 119, 120, 145, 146, 160, 163, 174 Generator, 19, 24, 27, 160 Genetic Engineering, 145, 149, 160 Genital, 65, 86, 160 Genotype, 16, 160, 176 Germ cell tumors, 155, 160 Germ Cells, 155, 160, 174, 175, 186, 187 Gestation, 28, 93, 160, 177, 178, 186 Gestational, 99, 160 Gigantism, 87, 160 Gland, 87, 122, 139, 160, 163, 168, 175, 177, 180, 182, 184, 186, 188 Glomerulus, 160, 172 Glucocorticoid, 52, 90, 160, 171, 178 Glucose, 20, 21, 25, 48, 91, 99, 118, 149, 154, 160, 162, 166, 183 Glucose Intolerance, 154, 160 Glucose tolerance, 20, 91, 160 Glucose Tolerance Test, 20, 160 Glycogen, 149, 160 Glycoprotein, 157, 161, 166, 190 Gonad, 155, 161 Gonadal, 9, 17, 18, 46, 59, 161, 186 Gonadorelin, 108, 109, 161, 168 Gonadotropic, 17, 84, 87, 159, 161 Governing Board, 161, 178 Grade, 155, 161 Graft, 161, 164, 172 Grafting, 161, 164 Graft-versus-host disease, 161, 172 Gram-negative, 149, 161 Granulosa Cell Tumor, 44, 161 Granulosa Cells, 159, 161, 165, 168 Growth factors, 15, 161 H Haptens, 140, 161, 181 Headache, 146, 161, 163, 178, 179 Health Services, 20, 161 Health Surveys, 46, 162

Heart attack, 147, 162 Hemoglobin, 141, 157, 162, 188 Hemoglobinuria, 118, 162 Hemolytic, 162, 188 Hemorrhage, 152, 161, 162, 186 Hemostasis, 162, 184 Hepatic, 160, 162 Hepatotoxic, 162, 168 Hereditary, 162, 183, 188 Heredity, 139, 160, 162 Heterogeneity, 140, 162 Hippocampus, 13, 153, 162, 187 Hirsutism, 10, 20, 21, 153, 162, 163 Histamine, 143, 153, 162 Homeostasis, 13, 22, 28, 162 Homologous, 162, 184 Hormonal, 7, 14, 15, 19, 22, 30, 34, 65, 92, 93, 95, 99, 123, 144, 152, 157, 162 Hormone Replacement Therapy, 7, 32, 33, 38, 58, 93, 163 Hormone therapy, 49, 101, 104, 163 Hospital Records, 26, 163 Human growth hormone, 8, 163 Hydrocephalus, 31, 53, 163, 166 Hydrogen, 82, 144, 147, 154, 163, 171, 175, 176, 180 Hydrolysis, 163, 166, 168, 177 Hyperandrogenism, 10, 163 Hyperlipidemia, 4, 163 Hyperplasia, 56, 93, 163 Hypersecretion, 50, 163 Hypersensitivity, 92, 140, 153, 163, 184 Hypertension, 4, 82, 83, 91, 147, 163, 166, 178 Hypertrichosis, 162, 163 Hypertrophy, 83, 87, 88, 94, 152, 163, 189 Hypnotherapy, 55, 67, 164 Hypnotic, 66, 144, 164, 188 Hypoglycemia, 37, 164 Hypogonadism, 10, 16, 18, 77, 164 Hypothalamic, 7, 9, 11, 13, 14, 16, 17, 19, 24, 27, 32, 33, 34, 35, 36, 37, 38, 40, 41, 42, 43, 44, 45, 47, 48, 49, 51, 52, 53, 55, 56, 59, 60, 61, 65, 66, 67, 84, 85, 88, 89, 94, 102, 164 Hypothalamic Hormones, 84, 88, 89, 94, 164 Hypothalamus, 11, 13, 16, 24, 84, 87, 88, 89, 94, 143, 146, 152, 154, 161, 164, 177, 179, 188 Hysterectomy, 92, 164

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Amenorrhea

I Id, 61, 68, 118, 122, 123, 124, 126, 132, 134, 164 Idiopathic, 16, 18, 164 Immune response, 22, 139, 142, 152, 161, 164, 184, 187 Immune system, 77, 87, 145, 164, 190, 191 Immunization, 164, 184 Immunodeficiency, 118, 164 Immunogenic, 164, 181 Immunologic, 164, 182 Immunology, 139, 140, 164 Immunosuppressive, 153, 160, 164 Immunotherapy, 145, 154, 164 Impairment, 28, 143, 164, 170 Implantation, 26, 95, 151, 164, 173 Impotence, 82, 164, 179 In situ, 11, 164 In Situ Hybridization, 11, 165 In vitro, 11, 12, 16, 21, 93, 148, 156, 165, 184 In vivo, 11, 23, 24, 165 Incision, 165, 167 Incontinence, 163, 165 Indicative, 98, 165, 175, 190 Induction, 11, 32, 44, 49, 60, 141, 142, 165, 175, 179 Inertia, 7, 165 Infantile, 165, 168 Infarction, 148, 165 Infection, 143, 145, 164, 165, 168, 186, 191 Infertility, 9, 10, 12, 13, 21, 25, 27, 30, 32, 41, 48, 53, 60, 77, 84, 86, 88, 94, 122, 146, 165 Inflammation, 5, 8, 139, 142, 159, 165, 172, 183, 187 Infusion, 165 Ingestion, 160, 165 Inhibin, 26, 39, 44, 45, 53, 165 Initiation, 165, 189 Innervation, 17, 165 Inotropic, 154, 165 Insecticides, 165, 176 Insight, 15, 166 Insomnia, 166, 178 Insulin, 10, 15, 20, 21, 25, 59, 99, 160, 166, 190 Insulin-dependent diabetes mellitus, 166 Insulin-like, 15, 166 Intermittent, 85, 166 Internal Medicine, 156, 166 Interstitial, 166, 172

Intestinal, 160, 166, 169 Intestines, 139, 143, 159, 166 Intoxication, 166, 191 Intracellular, 21, 24, 90, 146, 165, 166, 178, 180, 182 Intracranial Hemorrhages, 163, 166, 188 Intracranial Hypertension, 161, 163, 166 Intramuscular, 40, 166 Intravenous, 20, 50, 60, 165, 166 Intrinsic, 7, 22, 140, 166 Intrinsic Factor, 7, 166 Involuntary, 144, 157, 166, 172 Ion Channels, 24, 166, 173 Ion Transport, 166, 171 Ionizing, 157, 167, 181 Ions, 144, 154, 155, 163, 166, 167, 178 Ischemia, 144, 167 J Joint, 167, 187 K Karyotype, 47, 167 Kb, 114, 167 Kidney Disease, 78, 114, 119, 167 Kinetic, 12, 167 L Lactation, 13, 41, 50, 55, 60, 66, 83, 86, 87, 167, 175, 179 Laparoscopy, 28, 86, 136, 167 Laparotomy, 28, 167 Large Intestine, 154, 166, 167, 182, 185 Latent, 167, 178 Leiomyoma, 158, 167, 185 Lens, 167, 182 Leptin, 9, 11, 13, 19, 21, 22, 25, 35, 38, 45, 102, 167 Lesion, 38, 167 Lethargy, 163, 167 Leukemia, 33, 118, 167 Leukocytes, 146, 167, 171, 190 Leukopenia, 5, 167 Leuprolide, 44, 102, 167 Levonorgestrel, 23, 168, 174 Libido, 141, 168 Library Services, 132, 168 Ligament, 142, 168, 180 Lipid, 91, 149, 166, 168 Lipodystrophy, 10, 168 Lipolysis, 10, 168 Lisuride, 60, 168 Liver, 25, 139, 143, 144, 147, 153, 154, 157, 159, 160, 162, 168 Lobe, 84, 87, 88, 89, 94, 148, 163, 168, 179

Dictionary 199

Localized, 159, 162, 163, 165, 168, 177 Longitudinal study, 14, 32, 42, 48, 49, 168 Lumbar, 14, 168 Lupus, 5, 54, 68, 168, 187 Lupus Nephritis, 5, 168 Luteal Phase, 9, 11, 26, 93, 95, 168 Lutein Cells, 168, 179 Lymph, 144, 148, 155, 156, 168 Lymph node, 144, 148, 155, 168 Lymphoid, 169 Lymphoma, 118, 169 M Malabsorption, 118, 169 Malignancy, 155, 169 Malignant, 91, 118, 139, 142, 146, 155, 160, 169, 172, 181 Malignant tumor, 139, 169 Malnutrition, 25, 144, 169, 172 Mammary, 87, 169, 182, 187 Mandible, 4, 169, 182 Manic, 142, 145, 169 Manifest, 19, 169 Meat, 84, 88, 89, 169 Medial, 11, 169, 174 Mediate, 11, 154, 169 Mediator, 169, 184 Medical Records, 4, 163, 169 Medical Staff, 155, 169 Medicament, 85, 169, 187 MEDLINE, 115, 117, 119, 169 Medroxyprogesterone, 35, 39, 73, 93, 169 Medroxyprogesterone Acetate, 39, 93, 169 Medullary, 169 Melanocytes, 169 Melanoma, 118, 146, 169 Membrane, 24, 148, 150, 153, 156, 157, 158, 161, 166, 170, 171, 174, 176, 183, 189 Membrane Glycoproteins, 170 Memory, 141, 170 Menarche, 7, 49, 50, 92, 170 Meninges, 148, 152, 170 Menopause, 33, 38, 42, 54, 58, 91, 92, 93, 99, 104, 170, 178 Menorrhagia, 92, 123, 170 Menstrual Cycle, 7, 9, 11, 15, 18, 22, 36, 84, 87, 88, 92, 95, 104, 122, 124, 159, 168, 170, 178, 179 Mental deficiency, 158, 170 Mental Disorders, 79, 170, 180 Mental Health, iv, 8, 27, 51, 79, 114, 116, 170, 181 Metabolic disorder, 154, 170

Metabolite, 26, 170 Metoclopramide, 44, 170 MI, 43, 137, 170 Microbe, 170, 189 Microbiology, 144, 170 Microgram, 95, 170 Microscopy, 13, 170 Migration, 17, 170 Milligram, 170 Milliliter, 145, 170 Mineralocorticoid, 90, 170 Miscarriage, 29, 171 Modeling, 20, 171 Modification, 6, 7, 8, 160, 171, 181 Modulator, 9, 12, 171 Molecular, 11, 17, 21, 24, 39, 43, 45, 47, 115, 117, 145, 150, 153, 171, 179, 182, 190 Molecule, 12, 142, 144, 150, 154, 158, 163, 171, 175, 182 Monitor, 15, 123, 152, 171 Monocytes, 167, 171, 188 Morphogenesis, 158, 171 Morphological, 156, 169, 171 Morphology, 26, 171 Mosaicism, 32, 47, 171 Motility, 26, 171, 184 Motor nerve, 171 Mucosa, 168, 171, 179 Multicenter study, 10, 47, 171 Muscle Fibers, 171, 172 Muscle relaxant, 8, 171 Muscle tension, 171 Muscular Atrophy, 118, 172 Muscular Dystrophies, 155, 172 Mycophenolate mofetil, 5, 172 Myocardial infarction, 21, 152, 170, 172 Myocardium, 170, 172 Myometrium, 93, 172 Myotonic Dystrophy, 118, 172 N Naloxone, 59, 172 Naltrexone, 59, 172 Narcotic, 172 Nausea, 142, 143, 155, 172, 178 NCI, 1, 78, 113, 172 Necrosis, 148, 165, 170, 172 Need, 3, 5, 6, 97, 98, 103, 109, 127, 149, 161, 172, 189 Neoplasia, 118, 172 Neoplasm, 155, 172 Neoplastic, 169, 172 Nephritis, 5, 172

200

Amenorrhea

Nephropathy, 167, 172 Nerve, 140, 141, 143, 153, 165, 169, 171, 173, 183, 184, 186, 189 Nervous System, 24, 118, 140, 148, 156, 169, 173, 187 Neural, 17, 140, 147, 173 Neuroendocrine, 9, 11, 13, 16, 17, 19, 21, 22, 27, 35, 47, 173 Neuroleptic, 40, 142, 173 Neurologic, 163, 173 Neuronal, 11, 12, 13, 17, 27, 173 Neurons, 11, 13, 16, 17, 24, 149, 153, 158, 159, 171, 173 Neuropeptide, 12, 13, 147, 152, 173 Neurophysiology, 153, 173 Neurotransmitters, 173 Niacin, 173, 189 Nidation, 95, 156, 173 Nitrogen, 140, 141, 153, 159, 173, 189 Norepinephrine, 27, 140, 154, 173 Norethindrone, 95, 173 Norgestrel, 168, 173 Nuclei, 11, 156, 160, 174, 180 Nucleic acid, 165, 173, 174 Nucleus, 13, 143, 144, 153, 154, 158, 159, 171, 174, 179, 180, 187 Nutritional Status, 9, 46, 174 O Ointments, 155, 174 Oligo, 10, 20, 48, 52, 174 Oligomenorrhea, 21, 26, 42, 45, 59, 60, 86, 174, 177 Oncogene, 118, 174 Oocytes, 58, 174 Opacity, 153, 174 Opioid Peptides, 9, 155, 156, 174 Optic Chiasm, 164, 174 Osmotic, 174, 184 Ossification, 46, 174 Osteoporosis, 3, 4, 5, 6, 7, 32, 38, 41, 52, 53, 54, 55, 58, 91, 98, 104, 122, 124, 157, 174, 182 Ovarian Follicle, 77, 95, 152, 161, 174, 188 Ovariectomy, 40, 175 Ovaries, 21, 77, 158, 163, 175, 177, 182, 185 Ovary, 21, 39, 84, 90, 94, 152, 157, 159, 161, 174, 175 Overweight, 4, 61, 104, 175 Ovulation Induction, 61, 175 Ovum, 152, 160, 174, 175, 179, 191 Oxidation, 142, 175 Oxytocin, 164, 175

P Palliative, 153, 175, 188 Pancreas, 139, 145, 154, 166, 175, 190 Pancreatic, 118, 147, 175 Pancreatic cancer, 118, 175 Parkinsonism, 82, 83, 143, 168, 175 Paroxysmal, 118, 175 Partial remission, 5, 175, 182 Partial response, 175 Parturition, 175, 179 Patch, 38, 175 Pathogenesis, 27, 28, 175 Pathologic, 37, 145, 152, 163, 175, 182 Pathophysiology, 22, 175 Patient Education, 125, 130, 132, 137, 175 Pelvic, 86, 156, 175, 180 Penis, 151, 155, 176, 182 Peptide, 38, 43, 85, 87, 88, 89, 94, 146, 167, 174, 176, 177, 179, 180, 188 Pergolide, 83, 176 Pericardium, 176, 187 Peritoneal, 86, 176 Peritoneum, 176 Perivascular, 147, 176 Pernicious, 166, 176 Pernicious anemia, 166, 176 Pesticides, 25, 165, 176 PH, 145, 176 Pharmaceutical Solutions, 155, 176 Pharmacologic, 8, 25, 27, 28, 49, 60, 66, 141, 176, 189 Phenotype, 16, 176 Phenyl, 82, 176 Phospholipids, 158, 176 Phosphorus, 147, 176 Physical Examination, 15, 176 Physiologic, 10, 16, 22, 25, 140, 145, 170, 177, 179, 182 Physiology, 8, 12, 16, 22, 24, 28, 156, 173, 177 Pigment, 169, 177 Pilot study, 22, 23, 44, 55, 61, 177 Pituitary Gland, 87, 152, 161, 164, 177, 179 Pituitary Hormone Release Inhibiting Hormones, 164, 177 Pituitary Hormone-Releasing Hormones, 164, 177 Pituitary Hormones, 164, 177 Placenta, 157, 177, 179 Plants, 140, 146, 149, 160, 171, 173, 177, 183 Plaque, 143, 177

Dictionary 201

Plasma, 11, 30, 43, 59, 148, 159, 160, 162, 171, 177, 184 Plasma protein, 177, 184 Plasma Volume, 171, 177 Polycystic, 10, 20, 21, 36, 83, 87, 88, 90, 119, 163, 177 Polycystic Ovary Syndrome, 10, 20, 36, 83, 87, 88, 90, 163, 177 Polypeptide, 177, 179, 188 Posterior, 4, 141, 143, 154, 164, 175, 177, 178 Postmenopausal, 4, 30, 157, 174, 178, 182 Postnatal, 158, 178, 186 Postpartum Hemorrhage, 39, 178 Potassium, 24, 140, 171, 178 Potassium Channels, 24, 178 Potentiates, 18, 178 Practice Guidelines, 116, 178 Precipitating Factors, 148, 178 Precursor, 93, 143, 149, 153, 154, 156, 157, 173, 178, 179, 189, 190 Predisposition, 20, 178 Prednisolone, 5, 178 Pre-Eclampsia, 20, 93, 178 Pregnancy Outcome, 26, 178 Premenopausal, 6, 10, 30, 50, 52, 178 Premenstrual, 15, 83, 87, 88, 122, 123, 178 Premenstrual Syndrome, 83, 87, 88, 122, 178 Prenatal, 17, 156, 158, 179 Prevalence, 4, 6, 50, 59, 179 Progesterone, 11, 12, 23, 32, 50, 73, 90, 92, 93, 95, 102, 168, 173, 174, 179, 186 Progestogen, 92, 93, 179 Prognostic factor, 45, 179 Progression, 26, 141, 179 Progressive, 86, 95, 149, 157, 161, 172, 179 Projection, 13, 173, 179, 182 Prolactin, 13, 29, 36, 83, 86, 87, 136, 146, 179 Prolactinoma, 51, 83, 87, 179 Prone, 28, 179 Pro-Opiomelanocortin, 156, 174, 179 Prophase, 174, 179 Prophylaxis, 86, 179 Prospective Studies, 11, 179 Prospective study, 26, 66, 168, 179 Prostaglandin, 93, 179 Prostaglandins A, 180 Prostate, 84, 90, 118, 145, 180, 182, 190 Protease, 84, 150, 180 Protein S, 119, 145, 163, 180

Proteins, 140, 141, 142, 147, 148, 150, 171, 173, 176, 177, 180, 182, 184, 189 Proteinuria, 5, 36, 178, 180 Protocol, 19, 28, 30, 180 Protons, 163, 167, 180, 181 Proximate cause, 27, 180 Psychiatric, 3, 15, 30, 66, 170, 180 Psychiatry, 15, 28, 30, 45, 52, 159, 180 Psychic, 168, 180, 184 Psychogenic, 9, 28, 67, 180 Psychomotor, 18, 173, 180 Psychotherapy, 150, 181 Puberty, 11, 15, 16, 17, 24, 31, 39, 58, 59, 83, 84, 87, 88, 94, 181 Public Health, 20, 22, 25, 29, 30, 105, 116, 181 Public Policy, 115, 181 Pulmonary, 145, 151, 152, 181, 191 Pulmonary Artery, 145, 181, 191 Pulmonary hypertension, 152, 181 Pulsation, 85, 181 Pulse, 19, 24, 27, 85, 171, 181 Pustular, 139, 181 Q Quality of Life, 20, 181 R Race, 167, 168, 170, 174, 181 Radiation, 137, 157, 159, 167, 181, 191 Radioactive, 146, 163, 164, 181 Radiography, 4, 181 Radioimmunoassay, 12, 181 Radioimmunotherapy, 181, 182 Radiopharmaceutical, 160, 181 Radiotherapy, 53, 181 Raloxifene, 182, 184 Randomized, 10, 20, 22, 23, 155, 182 Rebound effect, 84, 88, 182 Receptor, 11, 12, 13, 17, 23, 30, 39, 40, 43, 82, 84, 88, 89, 90, 94, 142, 151, 154, 181, 182, 184 Receptors, Serotonin, 182, 184 Rectum, 143, 146, 154, 159, 165, 167, 180, 182, 187 Recurrence, 145, 182 Red Nucleus, 143, 182 Refer, 1, 4, 146, 150, 156, 159, 173, 181, 182 Refraction, 182, 186 Regimen, 5, 6, 7, 93, 155, 182 Relapse, 5, 182 Relaxant, 182 Remission, 145, 182 Reproduction Techniques, 178, 182

202

Amenorrhea

Reproductive system, 11, 43, 182 Resection, 50, 52, 60, 92, 182 Resolving, 92, 182 Resorption, 163, 182 Respiration, 153, 171, 182 Resting metabolic rate, 19, 35, 183 Retina, 167, 174, 183 Retinoblastoma, 118, 183 Retinopathy, 99, 183 Retrospective, 26, 29, 33, 58, 183 Retrospective Studies, 26, 183 Rhinorrhea, 179, 183 Risk factor, 4, 7, 148, 179, 183 Risperidone, 42, 52, 65, 73, 183 Rodenticides, 176, 183 S Salivary, 154, 175, 183 Salivary glands, 154, 183 Saponins, 183, 186 Schizoid, 183, 191 Schizophrenia, 183, 184, 191 Schizotypal Personality Disorder, 183, 191 Sclerosis, 118, 184 Screening, 6, 15, 124, 149, 184 Sebum, 139, 184 Secretory, 9, 16, 27, 95, 184 Sedentary, 4, 99, 183, 184 Seizures, 175, 184 Selective estrogen receptor modulator, 91, 182, 184, 187 Sella, 177, 184 Semen, 26, 70, 71, 72, 155, 180, 184 Seminiferous tubule, 165, 184, 186 Seminoma, 155, 184 Semisynthetic, 146, 158, 184 Senescence, 17, 184 Senile, 174, 184 Sensitization, 18, 184 Serology, 29, 184 Serotonin, 30, 40, 143, 153, 168, 182, 183, 184, 189 Serum, 5, 13, 18, 29, 33, 37, 44, 45, 84, 150, 161, 171, 181, 184, 190 Serum Albumin, 5, 181, 184 Sex Characteristics, 139, 141, 181, 184, 187 Sex Determination, 119, 185 Sexual Partners, 86, 185 Sexually Transmitted Diseases, 20, 185 Shock, 185, 189 Side effect, 4, 5, 8, 12, 90, 91, 93, 107, 109, 140, 143, 145, 153, 185, 189 Signs and Symptoms, 182, 185

Skeletal, 21, 53, 141, 153, 155, 172, 185, 188 Skeleton, 158, 167, 180, 185 Small intestine, 163, 166, 185, 191 Smooth muscle, 141, 146, 151, 158, 162, 167, 172, 185, 187 Smooth Muscle Tumor, 158, 185 Social Environment, 181, 185 Sodium, 140, 171, 185 Soft tissue, 145, 185 Solvent, 144, 157, 174, 176, 185 Somatic, 139, 185 Specialist, 126, 154, 185 Species, 16, 30, 149, 153, 157, 159, 167, 170, 181, 185, 187, 189, 191 Specificity, 140, 186 Spectrum, 16, 47, 186 Sperm, 16, 141, 149, 160, 184, 186 Spermatozoa, 184, 186 Spinal cord, 148, 149, 157, 170, 173, 186 Spontaneous Abortion, 26, 178, 186 Sporadic, 183, 186 Stem Cells, 20, 157, 161, 186 Sterility, 17, 32, 33, 35, 38, 39, 42, 43, 45, 46, 47, 48, 49, 51, 52, 53, 55, 56, 67, 153, 165, 186 Sterilization, 125, 186 Steroid, 43, 48, 63, 90, 93, 152, 183, 186 Stillbirth, 178, 186 Stimulant, 146, 153, 162, 186 Stimulus, 13, 151, 158, 165, 166, 186, 188 Stomach, 139, 154, 157, 159, 160, 163, 166, 172, 185, 186 Stress, 6, 7, 9, 11, 20, 25, 27, 35, 49, 58, 67, 75, 147, 152, 172, 178, 186 Stroke, 4, 79, 114, 147, 186 Stromal, 156, 186 Subclinical, 24, 26, 165, 184, 186 Subcutaneous, 139, 155, 167, 168, 187 Subiculum, 162, 187 Subspecies, 185, 187 Substance P, 170, 179, 184, 187 Substrate, 11, 187 Suppositories, 125, 160, 187 Suppression, 10, 13, 24, 25, 152, 187 Sympathomimetic, 154, 157, 173, 187 Symphysis, 180, 187 Symptomatic, 49, 142, 187 Symptomatic treatment, 142, 187 Synergistic, 179, 187 Systemic, 5, 50, 68, 92, 93, 108, 145, 157, 165, 166, 168, 178, 187, 189

Dictionary 203

Systemic lupus erythematosus, 5, 50, 168, 187 Systolic, 163, 187 T Tamoxifen, 30, 56, 184, 187 Telangiectasia, 119, 187 Temporal, 162, 187 Teratogenic, 17, 187 Testicular, 159, 187 Testis, 155, 157, 159, 187 Testosterone, 7, 10, 26, 65, 84, 187 Thalamic, 143, 187, 188 Thalamic Diseases, 143, 188 Thalassemia, 34, 188 Thalidomide, 54, 188 Theca Cells, 21, 168, 188 Therapeutics, 38, 109, 188 Thigh, 158, 188 Thinness, 104, 188 Third Ventricle, 143, 164, 188 Thorax, 139, 168, 188 Threshold, 22, 158, 163, 188 Thrombocytopenia, 56, 188 Thrombosis, 180, 186, 188 Thyroid, 33, 94, 123, 177, 188, 190 Thyroid Gland, 177, 188 Thyroid Hormones, 188, 190 Thyrotropin, 34, 84, 88, 89, 188 Thyroxine, 33, 188 Tolerance, 160, 188 Tomography, 145, 189 Tonic, 9, 189 Topical, 92, 93, 157, 189 Torsion, 53, 165, 189 Toxic, iv, 144, 153, 157, 162, 189 Toxicity, 5, 155, 189 Toxicology, 12, 116, 189 Trace element, 146, 149, 189 Trachea, 188, 189 Transcription Factors, 90, 189 Transfection, 145, 189 Translational, 20, 189 Transmitter, 85, 139, 154, 166, 169, 173, 189 Trauma, 50, 172, 189 Triad, 3, 4, 5, 6, 7, 32, 54, 55, 58, 66, 103, 189 Tricuspid Atresia, 151, 189 Trigger zone, 143, 189 Trivalent, 82, 189 Troglitazone, 10, 189

Tryptophan, 30, 184, 189 Tuberculosis, 151, 168, 189 Tuberous Sclerosis, 119, 189 Tumor marker, 145, 190 Tumor Necrosis Factor, 188, 190 Type 2 diabetes, 4, 190 Tyrosine, 154, 190 U Ultrasonography, 44, 190 Unconscious, 164, 190 Urethra, 176, 180, 190 Urinary, 26, 163, 165, 190 Urine, 5, 22, 23, 26, 136, 145, 152, 154, 162, 165, 180, 190 Uterus, 83, 87, 88, 93, 148, 152, 156, 158, 164, 167, 170, 172, 175, 179, 182, 190 V Vaccine, 139, 180, 190 Vagina, 148, 170, 182, 190 Vaginal, 12, 14, 32, 93, 123, 190 Vascular, 165, 174, 177, 188, 190 Vasodilator, 147, 154, 162, 190 Vasomotor, 157, 190 VE, 4, 190 Vegetarianism, 64, 190 Vein, 166, 190 Venous, 148, 180, 189, 190 Ventral, 143, 164, 190 Ventricle, 143, 151, 162, 181, 187, 188, 189, 190, 191 Ventricular, 151, 163, 189, 191 Venules, 145, 191 Veterinary Medicine, 115, 191 Villi, 163, 191 Virilism, 163, 191 Virulence, 189, 191 Vitro, 191 Vivo, 191 W Weight Gain, 8, 14, 19, 92, 191 White blood cell, 142, 167, 169, 191 Windpipe, 188, 191 Withdrawal, 6, 32, 91, 93, 191 Womb, 182, 190, 191 X Xenograft, 141, 191 X-ray, 6, 14, 145, 159, 181, 191 Y Yeasts, 176, 191 Z Zygote, 151, 171, 191

204

Amenorrhea