Hormone Replacement Therapy - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HORMONE REPLACEMENT THERAPY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFE...

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HORMONE

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 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., 1960Hormone Replacement Therapy: 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: 0-597-83929-8 1. Hormone Replacement Therapy-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 hormone replacement therapy. 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 HORMONE REPLACEMENT THERAPY ....................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hormone Replacement Therapy.................................................... 8 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND HORMONE REPLACEMENT THERAPY ........................................... 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Hormone Replacement Therapy................................................. 115 Federal Resources on Nutrition ................................................................................................. 120 Additional Web Resources ......................................................................................................... 120 CHAPTER 3. ALTERNATIVE MEDICINE AND HORMONE REPLACEMENT THERAPY..................... 123 Overview.................................................................................................................................... 123 The Combined Health Information Database............................................................................. 123 National Center for Complementary and Alternative Medicine................................................ 124 Additional Web Resources ......................................................................................................... 133 General References ..................................................................................................................... 136 CHAPTER 4. DISSERTATIONS ON HORMONE REPLACEMENT THERAPY....................................... 139 Overview.................................................................................................................................... 139 Dissertations on Hormone Replacement Therapy...................................................................... 139 Keeping Current ........................................................................................................................ 141 CHAPTER 5. CLINICAL TRIALS AND HORMONE REPLACEMENT THERAPY ................................. 143 Overview.................................................................................................................................... 143 Recent Trials on Hormone Replacement Therapy...................................................................... 143 Keeping Current on Clinical Trials ........................................................................................... 145 CHAPTER 6. PATENTS ON HORMONE REPLACEMENT THERAPY ................................................. 147 Overview.................................................................................................................................... 147 Patents on Hormone Replacement Therapy............................................................................... 147 Patent Applications on Hormone Replacement Therapy ........................................................... 164 Keeping Current ........................................................................................................................ 182 CHAPTER 7. BOOKS ON HORMONE REPLACEMENT THERAPY ..................................................... 183 Overview.................................................................................................................................... 183 Book Summaries: Federal Agencies............................................................................................ 183 Book Summaries: Online Booksellers......................................................................................... 188 The National Library of Medicine Book Index ........................................................................... 192 Chapters on Hormone Replacement Therapy............................................................................. 193 CHAPTER 8. MULTIMEDIA ON HORMONE REPLACEMENT THERAPY .......................................... 195 Overview.................................................................................................................................... 195 Video Recordings ....................................................................................................................... 195 Bibliography: Multimedia on Hormone Replacement Therapy ................................................. 196 CHAPTER 9. PERIODICALS AND NEWS ON HORMONE REPLACEMENT THERAPY ....................... 197 Overview.................................................................................................................................... 197 News Services and Press Releases.............................................................................................. 197 Newsletter Articles .................................................................................................................... 199 Academic Periodicals covering Hormone Replacement Therapy ............................................... 200 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 201 Overview.................................................................................................................................... 201 U.S. Pharmacopeia..................................................................................................................... 201 Commercial Databases ............................................................................................................... 202 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 205

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Overview.................................................................................................................................... 205 NIH Guidelines.......................................................................................................................... 205 NIH Databases........................................................................................................................... 207 Other Commercial Databases..................................................................................................... 209 APPENDIX B. PATIENT RESOURCES ............................................................................................... 211 Overview.................................................................................................................................... 211 Patient Guideline Sources.......................................................................................................... 211 Finding Associations.................................................................................................................. 219 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 221 Overview.................................................................................................................................... 221 Preparation................................................................................................................................. 221 Finding a Local Medical Library................................................................................................ 221 Medical Libraries in the U.S. and Canada ................................................................................. 221 ONLINE GLOSSARIES................................................................................................................ 227 Online Dictionary Directories ................................................................................................... 227 HORMONE REPLACEMENT THERAPY DICTIONARY..................................................... 229 INDEX .............................................................................................................................................. 301

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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 hormone replacement therapy 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 hormone replacement therapy, 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 hormone replacement therapy, 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 hormone replacement therapy. Abundant guidance is given on how to obtain free-ofcharge 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 hormone replacement therapy, 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 hormone replacement therapy. 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 HORMONE REPLACEMENT THERAPY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hormone replacement therapy.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hormone replacement therapy, 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 “hormone replacement therapy” (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: •

Hormone Replacement Therapy and Its Relationship to Lipid and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women Source: Diabetes Care. 25(10): 1675-1680. October 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Among postmenopausal women, those with diabetes experience more cardiovascular diseases than those without diabetes. In this study, the authors examined the relationship of hormone replacement therapy (HRT) with indicators of lipid and glucose metabolism using a national sample of postmenopausal women with and

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Hormone Replacement Therapy

without diabetes. The authors used data from the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. A total of 2,786 postmenopausal women aged 40 to 74 years participated in an oral glucose tolerance test (OGTT), had blood drawn for lipid (fats) assessment, and responded to HRT questions. The results showed that postmenopausal women with diabetes had increased dyslipidemia compared with nondiabetic women. Among diabetic women, current users of HRT had significant different lipid and glucose control levels than never users of HRT for the following variables: total cholesterol, non-HDL, apoA, fibrinogen, glucose, insulin, and glycosylated hemoglobin. The authors conclude that women with diabetes and nondiabetic postmenopausal women currently taking HRT had better lipoprotein profile than never or previous users of HRT. Women with diabetes currently taking HRT had better glycemic control than never or previous users of HRT. 3 tables. 29 references. •

Menopause: The Latest on Hormone Replacement Therapy Source: Diabetes Self-Management. 19(4): 90, 92, 95-97. July-August 2002. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Website: www.diabetes-self-mgmt.com. Summary: Hormone replacement therapy (HRT) is a medical therapy option that can alleviate and treat both the short-term symptoms and some of the long-term consequences of menopause. HRT can also increase the risk for certain health problems, so a menopausal woman and her physician need to consider her individual risk factors before starting HRT. This article discusses the benefits, risks, and alternatives to HRT for women with diabetes. Other topics include common symptoms of perimenopause and menopause, the long-term consequences of menopause, the effects of menopause on diabetes, the different types of HRT, the effects of HRT on diabetes, and alternative treatments.

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Secondary Hyperparathyroidism and Vitamin D Hormone Replacement Therapy: New Treatment Perspectives Source: Dialysis and Transplantation. 30(2): 109-111, 125. February 2001. Contact: Available from Dialysis and Transplantation, Attn.: Subscriptions. P.O. Box 10535, Riverton, NJ 08076. (800) 624-4196 or (609) 786-0871. Summary: Secondary hyperparathyroidism (SHPT) affects nearly all patients with chronic renal (kidney) failure (CRF). Recent evidence indicates that complications of SHPT are systemic, and not merely limited to renal bone disease. The link between SHPT and these co morbid conditions has prompted clinicians to make SHPT management a higher patient care priority. This article reviews the development of SHPT, the historical lack of appropriate treatment, and how vitamin D hormone replacement therapies could be used to prevent or limit its effects. In recent years, two vitamin D analogs that have been shown to be less calcemic, paricalcitol (Zemplar IV) and doxercalciferol (Hectorol oral and IV), have been approved for the treatment of SHPT in renal patients. Paricalcitol is active upon administration, with similar pharmacokinetic (how the drug works in the body) characteristics. However, doxercalciferol is a prohormone that, like endogenous vitamin D, must undergo metabolic transformation in the liver in order to form the active vitamin D hormone. This results in a pharmacokinetic profile that, at normal doses, provides blood levels of active vitamin D hormones that peak in 8 hours and remain in the physiologic range for

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more than 40 hours. This mimics the body's natural metabolism of vitamin D hormone, the ideal treatment for vitamin D hormone deficiency. 19 references. •

Effects of Postmenopausal Hormone Replacement Therapy on Central Abdominal Fat, Glycemic Control, Lipid Metabolism, and Vascular Factors in Type 2 Diabetes: A Prospective Study Source: Diabetes Care. 22(9): 1401-1407. September 1999. Contact: Available from American Diabetes Association, Inc. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 806-7801. Website: www.diabetes.org. Summary: This article describes a 12-month prospective study that examined the early and longer term effects of hormone replacement therapy (HRT) on lipid metabolism, glycemic control, total body and central abdominal fat, blood pressure, and arterial pulse wave velocity (APWV) in overweight postmenopausal females who had type 2 diabetes. Participants were 14 women who were randomized to 6 months of observation or open label HRT before crossover. HRT consisted of 2 months of conjugated equine estrogen (CEE) 0.625 milligrams daily, followed by 4 months CEE and medroxyprogesterone 5 milligrams daily. The study found that 6 months of HRT induced significant reductions in waist circumference, waist to hip ratio, glycosylated hemoglobin (HbA1c), total and low density lipoprotein cholesterol, and central abdominal fat. HRT also improved physical functioning. There was a minor increase in resting energy expenditure. Total fat mass, fasting glucose, insulin, triglyceride, apolipoprotein B, nonesterified fatty acids, resting blood pressure, APWV, and physical activity were unchanged. The article concludes that postmenopausal HRT in these overweight women who had type 2 diabetes was associated with a reduction in central adiposity and improvement in lipid metabolism and glycemic control without deterioration in weight status or cardiovascular parameters measured. Further study is needed to determine whether HRT induced improvements in these cardiovascular risk factors result in lower long term cardiovascular morbidity and mortality, as observed in nondiabetic women. 3 tables. 50 references. (AA-M).

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Hormone Replacement Therapy Is Associated with Better Glycemic Control in Women with Type 2 Diabetes Source: Diabetes Care. 24(7): 1144-1150. July 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a study that examined whether glycosylated hemoglobin (HbA1c) levels varied by current hormone replacement therapy (HRT) among women with type 2 diabetes. The population for the study was drawn from the Northern California Kaiser Permanente Diabetes Registry. Among women with type 2 diabetes, the 15,435 women who had HbA1c measured at least once became the final cohort for all analyses in the study. HRT and HbA1c were assessed by reviewing records in the health plan's computerized laboratory and pharmacy systems. Sociodemographic and clinical information was collected by survey. Among the cohort, 3,852 were currently using HRT before the HbA1c test. Among women currently using HRT, 62 percent were using unopposed estrogens, 36 percent were using opposed estrogen, and 2 percent were using progestins alone. Women currently using HRT were younger, leaner, better educated, and more likely to be non-Hispanic whites than women not using HRT. Mean HbA1c levels were significantly lower in women currently using HRT than in women not using HRT, and these differences increased

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after adjusting for age. No differences in HbA1c level were observed between women using unopposed estrogens and women using opposed estrogens. In a Generalized Estimating Equation model, which took into account patient clustering within physician and was adjusted for age, ethnicity, education, obesity, hypoglycemic therapy, diabetes duration, self monitoring of blood glucose, and exercise, HRT remained significantly and independently associated with decreased HBA1c levels. The article concludes that HRT was independently associated with decreased HbA1c level. Clinical trials will be necessary to understand whether HRT may improve glycemic control in women with diabetes. 1 figure. 2 tables. 37 references. (AA-M). •

Hormone Replacement Therapy and Cognition: Systematic Review and Meta-analysis Source: JAMA. Journal of the American Medical Association. 285(11): 1489- 1499. March 21, 2001. Summary: This article presents a systematic review and meta-analysis of studies examining the relationship between hormone replacement therapy (HRT) and the risk of cognitive decline and dementia. Randomized controlled trials and cohort studies were reviewed for the effects of HRT on cognitive decline; cohort and case-control studies were reviewed for dementia risk. No randomized controlled trials regarding dementia risk were found. Twenty-nine studies met inclusion criteria and were rated for quality. Studies of cognition could not be combined quantitatively because of differences in study design. However, results suggested some benefits of HRT for verbal memory, vigilance, reasoning, and motor speed in women with menopausal symptoms but not in asymptomatic women. A meta-analysis of observational studies suggested that HRT is associated with a decreased risk of dementia, but most studies had important methodological limitations. 1 figure, 5 tables, 67 references.

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Hormone Replacement Therapy, Insulin Sensitivity, and Abdominal Obesity in Postmenopausal Women Source: Diabetes Care. 25(1): 127-133. January 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to determine whether insulin sensitivity differs between postmenopausal women taking estradiol, women on estrogen plus progesterone hormone replacement therapy (HRT), and women not on HRT and whether differences are explained by the differences in total or abdominal adiposity and fat deposition in the muscle. The authors studied 28 obese, sedentary postmenopausal Caucasian women. Women taking oral estrogen (n = 6) were matched for age, weight, and body mass index (BMI) with women not on HRT (n = 6). Eight women taking oral estrogen plus progesterone were matched with eight different women not on HRT for age, weight, and BMI. Maximal aerobic capacity, percentage of fat, total body fat mass, and fat-free mass (FFM) were similar between groups. Visceral fat, subcutaneous abdominal fat, sagittal diameter, and mid thigh low density lean tissue (intramuscular fat) did not differ by hormone status. Basal carbohydrate and fat utilization was not different among groups. Fasting plasma glucose and insulin did not differ by hormone use. Glucose utilization (M) was measured; postmenopausal women taking oral estrogen had a 31 percent lower M than women not on HRT. M was 26 percent lower in women taking estrogen plus progesterone than women not on HRT. M per I, the amount of glucose metabolized per unit of plasma insulin (I), an index of insulin sensitivity, was 36 percent lower in women taking estrogen compared with matched

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women not on HRT and 28 percent lower in women taking estrogen plus progesterone compared with matched women not on HRT. The authors conclude that postmenopausal women taking oral estrogen or those taking a combination of estrogen and HRT are more insulin-resistant than women not on HRT, even when women are of comparable total and abdominal adiposity. 1 figure. 3 tables. 49 references. •

Hormone Replacement Therapy and Its Potential Relationship to Dementia Source: Journal of the American Geriatrics Society. 44(7): 878-880. July 1996. Summary: This journal article examines the potential role of estrogen replacement therapy in the prevention of dementia and issues in designing suitable clinical trials. The author reviews current evidence of the association among estrogen and dementia and concludes that the potential effects of estrogen on vascular disease appear to have the greatest likelihood of reducing the risk of dementia, especially if there is an association between vascular disease, beta-amyloid, and the development of Alzheimer's disease (AD). However, he cautions that any role of estrogen therapy, or even high endogenous estrogen levels, in preventing dementia related to either vascular dementia or AD has not been established. The author suggests that the critical question is how best to test the hypothesis that estrogen therapy will reduce the risk or progression of dementia among older women. In designing trials of estrogen therapy, researchers must decide what population should be studied, what the necessary sample size is, how long participants should be followed, and what endpoints should be measured. In primary prevention trials, the main problem is the relatively low incidence of dementia and, especially, AD in the population. To fix this problem, larger sample sizes and a longer followup period are needed than those used in secondary prevention trials. However, the author concludes that such trials are needed and may be worth the difficulties and costs involved. 34 references.

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Hormone Replacement Therapy or Prophylaxis in Postmenopausal Women with Recurrent Urinary Tract Infection Source: Journal of Infectious Diseases. 183(Supplement 1): S74-S76. March 1, 2001. Contact: Available from Journal of Infectious Diseases. University of Chicago Press, Journals Division, P.O. Box 37005, Chicago, IL 60637. (773) 753-3347. Fax (773) 753-0811. E-mail: [email protected]. Website: www.journals.uchicago.edu. Summary: Urinary tract infection (UTI) is the most common bacterial infection in women, and it occurs with much greater frequency among elderly than among younger women and with increasing frequency among postmenopausal women. This article explores the role of hormone replacement therapy (HRT) as prophylaxis (preventive therapy) in postmenopausal women with recurrent UTI. The author reviews the related literature and concludes that estrogen replacement is effective not only in the treatment of urogynecological symptoms related to menopause but also in the prevention of recurrent UTIs. Younger postmenopausal women can benefit from oral hormonal therapy, which improves clinical symptoms related to menopause and helps avoid osteoporosis and ischemic heart disease; the use of vaginal estrogen should be limited to women older than 60 years for the treatment of atrophic vaginitis, recurrent UTIs, and urge incontinence. The use of HRT, including vaginal therapy, is contraindicated in women with active venous thromboembolism, severe active liver disease, and endometrial and breast carcinoma (cancer) but can be administered to women with diabetes, gallstones, and other relative contraindications. The author calls for additional

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studies evaluating the safety and comparative efficacy of oral and vaginal estriol. 1 figure. 10 references.

Federally Funded Research on Hormone Replacement Therapy The U.S. Government supports a variety of research studies relating to hormone replacement therapy. 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 hormone replacement therapy. 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 hormone replacement therapy. The following is typical of the type of information found when searching the CRISP database for hormone replacement therapy: •

Project Title: A MAYO COHORT STUDY OF MAMMOGRAPHIC BREAST DENSITY Principal Investigator & Institution: Vachon, Celine M.; Assistant Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The interindividual variability in breast tissue on mammographic images, as defined by several measures of mammographic breast density, has been shown to be a major risk factor for breast cancer. However, there are several limitations in the studies performed to date; they have involved older mammogram images from multiple institutions, using mostly subjective measures on one view of the breast. Also, none of these studies have incorporated biological samples into their analyses and very few have examined other features that may be more predictive of breast cancer risk. Our GOAL is to conduct a large-scale, prospective study at one institution with new mammography to examine the causal association of breast density with breast cancer and to identify new markers of breast cancer risk. The Mayo Mammography Clinic performs approximately 35,000 screening mammograms per year; 25,000 of these are from Minnesota, Wisconsin and Iowa. Over a three-year period, we will enroll 20,700 cancer-free women from this tri-state region into our mammography cohort study. We will collect complete risk factor information from a baseline questionnaire, modern mammogram films and biological samples and will follow participants/members for breast cancer incidence and mortality. We will use a semiautomated algorithm to estimate percent breast density, rate of change of percent density over time, dense area and regional density on members of our cohort. We propose to examine aspects of breast density with incidence of breast cancer;

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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specifically, we will examine percent breast density, novel features of the mammogram including regional density, total dense area and longitudinal rate of change of breast density. Additionally, we will ascertain machine variability and settings (kVp, mAs, compression, thickness) from mammogram films and incorporate into the above analyses. As secondary aims, we also propose to investigate the heterogeneity of change in breast density among women who initiate hormone replacement therapy (HRT). The literature shows that approximately 30 percent of women experience increases in breast density upon HRT initiation. We propose to examine whether there is an association between this change in breast density and risk of breast cancer and also whether there is an association between this change and four functional polymorphisms in the genes SULT1A1, SULT1E1 and CYP3A5. The findings from these proposed studies have obvious translational implications: high-risk groups can be identified for intervention, more aggressive surveillance and perhaps chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A ONE YEAR ESTROGEN/PROGESTIN IMPLANT Principal Investigator & Institution: Nichols, L D.; Biotek, Inc. 21-C Olympia Ave Woburn, Ma 01801 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 28-FEB-2004 Summary: (provided by applicant): This program targets a one-year biodegradable estrogen/progestin implant for postmenopausal hormone replacement therapy. Estradiol plus levonorgestrel will be incorporated into an innovative implant design already being developed by BIOTEK for delivery of pure levonorgestrel as a maintenance contraceptive. The implant consists of a drug-free, biodegradable polymer core surrounded by a drug-containing shell, which provides efficient drug delivery. Such implants will biodegrade if left in place for more than a year, yet they can be surgically removed before the end of a year if necessary. With no need to keep track of daily pills or weekly patches, and with little reason to fear an unpleasant removal episode, such implants should provide a welcome new form of sustained hormone replacement therapy. Phase I demonstrated the feasibility of delivering estradiol and levonorgestrel at acceptable rates from the same implants. Phase II will now modify the core polymer to accelerate degradation, improve production methods, characterize promising designs in vitro, and confirm performance in rabbits. PROPOSED COMMERCIAL APPLICATION: The proposed work should lead to the development of a new kind of long lasting, highly effective, biodegradable drug delivery implant. Once fully impemented, implants of similar design should be useful for many other kinds of drug maintenance therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGE AND CONTROL OF HUMAN SKIN BLOOD FLOW Principal Investigator & Institution: Kenney, W. L.; Professor of Physiology and Kinesiology; Noll Physiological Res Ctr; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): In men and women over the age of 65, the non-acral skin blood flow (SkBF) response to hyperthermia is significantly attenuated. The site of this age-related defect involves the active vasodilator system, a non-adrenergic efferent pathway unique to human skin. The proposed series of studies will systematically examine potential mechanisms through which the negative effects of

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aging and the positive effects of estrogen therapy are exerted. In older and younger men and women and in post-menopausal women taking various types of hormone replacement therapy or no therapy, the PI plans to (a) examine spatial distribution and heterogeneity of active cutaneous vasodilation to determine whether changes in functional capillary plexus unit density and/or flow contribute to alterations in SkBF using scanning laser-Doppler imaging; (b) examine the magnitude, spatial distribution, and heterogeneity of reflex-mediated noradrenergic cutaneous vasoconstriction during whole-body cooling and baroreceptor unloading using scanning laser-Doppler imaging; and (c) determine the role of nitric oxide (NO) in the control of active vasodilation by examining NO-dependent and independent changes in SkBF during hyperthermia using intradermal microdialysis. In addition, a fourth series of studies is proposed to quantify the upper limit of the prescriptive zone (ULPZ) and age-specific heat exchange coefficients in older versus younger healthy men and women during low-intensity activity. Data from this last proposed investigation operationalizes the SkBF decrement to allow policy-making by health organizations and for modeling biophysical and physiological responses of the elderly to extreme environments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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in age-related breathing disorders that affect both men and women such as obstructive sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING & HEMODYNAMICS OF HYPERTHERMIA IN HRT & HYDRATION IN POSTMENOPAUSE Principal Investigator & Institution: Kenney, William L.; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: The hemodynamic responses of postmenopausal women to passive heat stress have not been characterized to date. This proposal outlines two studies which seek to characterize postmenopausal women's hemodynamic responses to passive heating through an investigation of the separate roles of hormone replacement therapy and hydration. It is the purpose of the second investigation in this proposal to examine the role of hydration on postmenopausal women's responses to passive heating. It is hypothesized that: 1) hydration will increase cardiac output; and 2) hydration with a commercially available sports drink will be better than hydration with water. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGING AND HYPERTENSION--GENDER, GENES AND RISK Principal Investigator & Institution: Fisher, Naomi D.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract). This application is for a Mentored Clinical Scientist Development Award. The applicant states that that sexual dimorphisms in cardiovascular risk evolve with increasing age, and that women experience significantly less hypertension and heart disease than do men -- though this difference disappears with increasing age, especially among Blacks. The research plan in this proposal aims to pursue preliminary evidence which suggests that age, gender and race play a key role in modifying the ultimate expression of genetic risk. In particular, preliminary data reveal that females are protected against expression of a common intermediate phenotype of essential hypertension, marked by abnormal responsiveness to angiotensin II. And among the many genes proposed to cause human hypertension, one of the very few for which linkage has been documented is that coding for angiotensinogen (AGT), a key element of the renin-angiotensin system - yet linkage has been convincingly shown only in males. The present proposal aims to test the hypothesis that the ultimate expression of the AGT gene is strongly influenced by age, gender, and hormonal status. It will test whether female hormone replacement therapy (HRT) can confer the same protection as do endogenous sex steroid hormones; whether race influences the relationship between AGT genotype and the phenotype of AngII responsiveness; and whether nutritional factors, ultimately involving obesity, contribute. With anticipated award the applicant's plan is to continue clinical research in hypertension, applying techniques and understanding of renal and adrenal physiology to the process of aging. Controlled physiologic studies by her will be performed on the Clinical Research Center of the Brigham and Women's Hospital. As well, she will be mentored by Dr. Lewis Lipsitz who is experienced in cardiovascular function and disease in the aging populations. The applicant's stated goal is to establish for herself an independent research career path for studying cardiovascular, renal, and adrenal function in relation to the pathogenesis of hypertension in the elderly.

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

Project Title: ALTERNATIVE THERAPIES FOR MENOPAUSE: A RANDOMIZED TRIAL Principal Investigator & Institution: Newton, Katherine M.; Associate Investigator; Center for Health Studies Seattle, Wa 98101 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-NOV-2004 Summary: (Adapted from Investigator's Abstract) Hormone replacement therapy (HRT: estrogen and progestin) remains the treatment of choice for women with vasomotor symptoms, and long-term HRT has been recommended for prevention purposes. The demand for alternatives to HRT, and the availability and use of over-the-counter products including dietary phytoestrogen supplements and naturopathic medicines, has grown dramatically. Few of these products have faced the rigors of randomized trials and none have been tested to evaluate their effects on long-term outcomes. The purpose of this four-year randomized controlled trial is to evaluate the efficacy and safety of three alternative approaches utilizing phytoestrogens to treat vasomotor symptoms in peri- and postmenopausal women. The treatments were chosen because of the scientific evidence supporting a possible benefit, the availability of products with adequate quality control their frequency of use in naturopathic medicine, and our ability to blind participants to the intervention. The five proposed treatment arms are as follow: 1) esterified estrogen and micronized progesterone: 9) a single herbal product, black cohosh; 3) a multibotanical preparation; 4) a combination regimen that includes the same multibotanical preparation plus soy diet counseling; and 5) placebo. The primary aim is to compare the effects of three alternative treatments, HRT, and placebo on the frequency and intensity of vasomotor symptoms measured by The Wiklund Menopause Symptom Checklist and a daily Vasomotor Symptom Diary. The secondary aims are to compare the effects of three alternative treatments, HRT, and placebo on the following: 1) vaginal cytology (vaginal maturation index); 2) serum lipids (total cholesterol, HDL and LDL cholesterol, triglycerides); 3) bone mineral density (hip and spine dual energy x-ray absorptiometry scan); 4) glucose metabolism (insulin, fasting blood glucose); and 5) coagulation factors (fibrinogen, PAI-1). The hypotheses are that compared to placebo the three alternative treatments tested in this study will have the following effects: reduce frequency of hot flashes and night sweats, improve vaginal maturation and decrease vagina atrophy as measured by maturation index, lower total cholesterol and LDL with no effect on HDL, reduce the rate of decline in bone mineral density (BMD), and have no effect on glucose metabolism or clotting factors. To accomplish the specific aims the investigators propose to do the following: 1) recruit and randomize 400 periand post-menopausal women to one of five treatment arms for one year; 2) collect measurements of primary and secondary outcomes at baseline, three, six, and 12 months; and 3) compare changes in outcomes in the groups taking alternative treatments to those in the HRT and placebo groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALZHEIMER'S DISEASE AND ESTROGEN REPLACEMENT Principal Investigator & Institution: Petitti, Diana B.; Director; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 94612 Timing: Fiscal Year 2003; Project Start 01-MAY-1998; Project End 31-JUL-2008 Summary: In 1999, 3,924 women age 75+ years who were categorized as users (N=1944) or non-users (N=1980) of hormone replacement therapy (estrogen alone--ERT; estrogen

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plus progestin--HRT) based on computer-stored prescription data were recruited to a study of the prevalence and incidence of dementia in relation to ERT/HRT use. At recruitment, cognitive status and dementia (all dementia and probable Alzheimer's Disease--AD) were assessed using the modified Telephone Interview of Cognitive Status (TICSm), the Telephone Dementia Questionnaire (TDQ) and medical record review. ApoE genotype was determined for the 2,044 women who gave blood and consented to testing. The prevalence of cognitive impairment and dementia in relation to ERT/HRT use was assessed, and the results of this analysis were published. Non-demented women who completed the TICSm at baseline have been followed annually in order to ascertain incident cases of dementia and to track changes in cognitive status based on the TICSm. To date, we have completed 2 of 4 planned years of follow-up; 182 incident cases of dementia have been identified. The study still lacks power to assess dementia in subgroups of importance. The period of follow-up to assess changes in cognitive functioning is so far short. Thus, we propose to continue follow-up of women in the cohort for an additional four years. The primary aims of continuation of the cohort study are: 1) to increase the power of the study to assess dementia and probable AD in relation to ERT/HRT use; 2) to increase the power of the study to examine dementia and probable AD risk in relation to ERT/HRT in specific subgroups; and 3) to assess rates of cognitive decline in ERT/HRT users overall and in subgroups. The study will also maintain its bank of DNA and pursue promising genetic leads in dementia and lateonset AD, although there are no specific plans to conduct additional gene tests proposed now. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIESTROGENS--MECHANISM OF ANTAGONIST ACTION Principal Investigator & Institution: Katzenellenbogen, Benita S.; Swanlund Professor; Molecular & Integrative Phys; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-DEC-1978; Project End 29-FEB-2004 Summary: Antiestrogens (AEs) are the most widely used agents for the treatment of hormone-responsive breast cancer, and the AE tamoxifen has also proven to be effective in preventing breast cancer. AEs are also unique ligands useful for understanding the tissue selective actions of certain estrogens, an important issue in menopausal hormone replacement therapy, and for probing the intriguing pharmacology of the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, and their roles in breast cancer and other estrogen target cells. In this application, we are proposing to investigate two new aspects of the action of AEs. The first aspect deals with the ability of certain proteins (denoted PAAs for "Potentiators of Antiestrogen Activity") that we have identified recently, to enhance the potency of AEs as inhibitors of estrogens. The levels and activity of these small, estrogen receptor-selective proteins could account for the differential tissue selectivity of AEs and for the ability of ER-containing breast tumors to be either highly sensitive, or resistant to AE therapy. We propose to identify and characterize PAAs, by examining their roles as modulators of AE action in target cells and determinants of hormonal resistance in breast cancer, by elucidating their interaction domains with ER, their subcellular distribution, and their interaction with other ER coregulators, and by performing structural analyses on PAA-ER complexes. The second aspect also derives from our recent work in which we have found that certain antioxidant/cytoprotective genes are upregulated by AEs and inhibited by estrogens. We propose to identify and analyze the regulation of genes selectively upregulated by AEs, by searching for other genes that are AE stimulated and estrogen suppressed, by

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analyzing the gene regulatory regions mediating the selective activation by AEs, by determining the ERalpha and ERbeta selectivity of this regulation, and by examining whether other antioxidant genes involved in cytoprotection against reactive oxygen species are upregulated by AEs. The studies we propose should provide significant new insight into how AEs act, what cellular factors determine their effectiveness and tissue selectivity, and how their gene regulating activities contribute to their beneficial antiproliferative, tumor suppressive, and cytoprotective actions in breast cancer treatment and prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE RESPONSE TO SOY ISOFLAVONES IN WOMEN Principal Investigator & Institution: Alekel, Lee D.; Food Science & Human Nutrition; Iowa State University of Science & Tech Ames, Ia 500112207 Timing: Fiscal Year 2002; Project Start 24-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): Soy protein rich in isoflavones (estrogen-like compounds) has been shown to prevent bone loss in ovariectomized rats. Our shortterm preliminary study results in perimenopausal women are compelling, suggesting a bone-sparing effect. These findings have prompted great interest in isoflavones as an alternative to hormone replacement therapy, yet the long-term efficacy of isoflavones on bone in humans is unknown. Our objective is to determine the three-year efficacy of isoflavone-rich soy extract in attenuating bone loss in postmenopausal women. The central hypothesis is that soy isoflavones will attenuate bone loss in early postmenopausal women by maintaining bone formation, being modulated by growth factors and isoflavone metabolism. The rationale for this research is that current hormone therapy is fraught with side effects that adversely affect women, resulting in non-compliance. This randomized double-blind placebo controlled clinical trial will examine the effects of two doses (80 or 120 mg/d) of isoflavone-rich soy extract on bone in non-osteoporotic early postmenopausal women (N=234). Specific Aims are to: 1) Determine the bone-preserving effects of isoflavones on lumbar spine bone mass as the primary outcome; 2) Relate treatment-induced changes in bone mass to changes in biochemical markers of bone turnover; 3) Identify potential mechanisms by which isoflavones prevent or modulate bone loss by measuring endogenous estrogens, sex hormone-binding globulin, insulin-like growth factor-I (IGF-I), urinary minerals, serum 25(OH)vitamin D, plasma isoflavones and their metabolites, and customary intake of isoflavone-containing soy, thus accounting for variability in response to treatment; 4) Ascertain the safety of isoflavone-rich soy extract. Caucasian women of European descent will be recruited at two sites (117 at IA, 117 at CA). Random effects repeated measures analyses will be used to: a) characterize change in bone mass as the primary outcome, b) estimate treatment-induced effects, and c) depict change in markers of bone turnover in relation to bone mass change. We will use intent-to-treat for the primary test. We will also examine potential modulators (reproductive hormones, IGF-I, plasma isoflavones) and account for other factors that affect bone, as indicated in specific aim 3. This study will provide valuable data on whether isoflavones impact bone in early postmenopausal women and help elucidate potential mechanisms, thereby contributing to our understanding of isoflavones as an alternative to traditional hormone therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BREAST & OTHER CANCER IN THE CALIFORNIA TEACHERS COHORT Principal Investigator & Institution: Wright, William E.; Chief; Public Health Institute 555 12Th St, 10Th Fl Oakland, Ca 94607 Timing: Fiscal Year 2001; Project Start 25-SEP-1998; Project End 30-SEP-2003 Summary: (adapted from applicant's Description): A cohort of 133,000 California school teachers has been established by a collaborative group of epidemiological investigators with the goals of evaluating unresolved issues related to breast cancer risk factors and studying other important issues related to women's health. The teachers were recruited with a detailed multiple choice, optically-scanned mail survey. Scanning of the questionnaires has been completed and data editing is ongoing. Planned follow-up includes routine linkage with the California Cancer Registry and California mortality files, annual re-contact of cohort members for follow-up, and biennial contact for collecting additional risk factor exposure data and information on other health outcomes. The Specific Aims for this project are to: 1) test a series of unresolved and emerging hypotheses related to breast cancer aetiology (specifically associations with the lactation, hormone replacement therapy, abortion/miscarriage, dietary phytoestrogens, fibre, micronutrient consumption, alcohol intake, physical exercise and activities, family history of breast and other cancers, and active and passive cigarette smoke exposure); 2) conduct calibration/validation studies of the food-frequency questionnaire and self-reported information on family history of breast and other cancers reported in the baseline questionnaire; and 3) follow this cohort for five additional years, during which time, two or more questionnaires will be mailed to update initial exposure assessments, collect new exposure information, and assess additional disease outcomes for testing novel hypotheses of major importance to women's health, in a timely manner. During the next five years, 2,025 invasive incident and 390 in situ incident breast cancers are anticipated which will provide ample statistical power to address each of the proposed hypotheses in detail. The California Teachers Study presents a rare opportunity to study women's health, because of the size of the cohort, the uniformly high level of education among teachers, their experience with survey instruments, their diversity of exposures and geographic residences, and the relative ease with which they can be followed in California. This research is intended to substantially increase knowledge of preventable risk factors for cancer and other health outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BREAST CANCER ETIOLOGY Principal Investigator & Institution: Gupta, Ramesh C.; Professor of Toxicology; Prev Med & Environmental Hlth; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 06-DEC-2001; Project End 30-NOV-2005 Summary: PROVIDED BY APPLICANT) A number of risk factors, including dietary fat intake, family history, and exposure to exogenous and endogenous chemicals, have been implicated in the etiology of breast cancer incidence. Epidemiological studies have identified an association of elevated levels of estrogens with breast cancer development. In particular, the natural hormone, 17B-estradiol (E2) and its major metabolite, 4hydroxyestradiol (4-E2), which are known animal carcinogens, have been implicated in human breast cancer and it is believed that these substances cause free radical-mediated, direct and/or indirect DNA damage. Novel, polar DNA adducts have been detected in

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the mammary tissues of both rats and humans by devising new systems to employ 32Ppostlabeling/TLC. Adduct spectra between rat and human mammary DNA exhibited strong similarities. Further, the polar adducts were significantly enhanced in estrogensensitive tissues, particularly mammary, after treatment of S/D rats with estradiol. In light of the known redox-cycling activity of 4-E2, a major metabolite of estradiol, these results suggest a link between polar DNA adduct formation and metabolic processing of E2. We hypothesize that the polar DNA adducts detected in the mammary tissues originate from free radical mediation. We also hypothesize that significant inter-subject differences occur in the accumulation of pre-mutational DNA lesions, and these differences could in part explain the wide range of susceptibility seen in the induction of some cancers. Specific studies will be as follows: (1) To analyze DNA damage in mammary epithelium of rats treated with the endogenous estrogen and its metabolites, as well as the equine estrogen, equilin and equilenin. Blood lymphocytes will be included as surrogates for comparison. Antioxidant intervention experiments will be performed to support the hypothesis. Also measured will be the tissue and plasma levels of E2 and its metabolites by sensitive HPLC-CoulArray for correlating with oxidative DNA adduct burden. (2) To analyze DNA damage in epithelial cells of breast tissues of cancer-free women and breast cancer patients and surrogate blood lymphocytes, and blood lymphocytes of women receiving hormone replacement therapy. Tissue levels of E2 and its metabolites will be correlated with oxidative DNA adduct burden and breast cancer incidence. (3) To develop and apply LC-MS/MS and CE-MS/MS technology in conjunction with 32P-postlabeling for identifying DNA adducts in human breast tissues. Data resulting from this highly sensitive approach will reveal the etiological nature of exposure and will determine inter-subject differences in mammary DNA damage that may be associated with susceptibility differences. Furthermore, if tissue levels of estradiol metabolite(s) and/or oxidative burden are found to correlate positively with breast cancer incidence, then future clinical studies to reduce breast cancer risks can be planned with antioxidant intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITION AND ESTROGEN IN MIDDLE-AGED FEMALE MONKEYS Principal Investigator & Institution: Voytko, Mary L.; Associate Professor; Pathology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2003; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (provided by applicant): This application is being submitted as a supplement to grant RO1AG19100 entitled "Cognition and Estrogen in Middle-Aged Female Monkeys". Ovarian hormone deficiency of menopause brings on changes that can have far reaching consequences on the future health and well being of women. In addition to the physical symptoms associated with menopause, postmenopausal women experience alterations in cognitive function, particularly memory and attention. However, determining the relationship between ovarian hormones and cognitive function in menopause can be difficult to study in women because of a variety of confounding factors. We have developed a monkey model of menopause that allows us to more rigorously control many of these factors and, additionally, that will permit us to identify the potential mechanisms of ovarian hormone action in the primate brain. The focus of the studies in the parent project is to determine the effects of ovariectomy and unopposed continuous estrogen replacement therapy (ERT) on cognitive abilities in a unique colony of middle-aged female rhesus monkeys at the Oregon Regional Primate Research Center (ORPRC). The purpose of this supplemental application is to expand

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the breadth of valuable information that could be obtained from the parent project by adding another group of ovariectomized monkeys that will be treated with a combined therapy of continuous estrogen and progesterone (HRT) and by performing MRI studies in all monkeys (supplemental and original groups). The addition of the new group of monkeys will permit the direct comparison between ERT and HRT treatments on cognitive function. Combined HRT is not only the most commonly prescribed ovarian hormone replacement therapy of postmenopausal women; it also represents a hormone replacement therapy that more closely mimics the natural physiological exposure to estrogen and progesterone in premenopausal women than continuous unopposed ERT alone. The MRI studies will determine the extent to which ovariectomy or ovarian hormone therapy influence measures of brain volume that decline with age, and whether there is a correlation between these volumetric changes and cognitive function. The experiments in this supplemental application will address key issues of women's health by taking advantage of the existence of the treatment and control groups already supported by the parent grant. The findings from these novel experiments in middleaged monkeys will significantly advance our understanding of the effects of different ovarian hormone therapies on cognitive and neurobiological profiles of primates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLON CANCER SURVIVORS--MEDICATIONS & RISK OF RECURRENCE Principal Investigator & Institution: Johnson, Christine C.; Ch Epidemiologist; Josephine Ford Cancer Center; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Applicant's Abstract): Colorectal cancer will be diagnosed in over 129,000 Americans in 1999. To combat this disease, new avenues to decrease the risk of colorectal cancer, such as chemoprevention, are being explored by researchers. Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone replacement therapy (HRT) have been shown to decrease incident colon cancer. Little is known of their effect on persons with a history of colon cancer which, fortunately, is a continually expanding population as survival has been significantly improving over the last twenty years. The objective of this epidemiologic study is to determine whether NSAIDs or HRT is associated with recurrence or survival among individuals diagnosed with colorectal cancer. The proposed research will establish a cohort of colorectal cancer patients treated with curative intent and create a comprehensive longitudinal database, including data on the ascertainment of subsequent adenomatous polyps, colorectal cancer and survival. The specific aims are: (1) to determine whether NSAID use deceases the risk of recurrence of colorectal cancer; (2) to determine whether HRT use deceases the risk of recurrence of colorectal cancer; (3) to determine whether NSAID use affects short-term survival; and (4) to determine whether HRT use affects short-term survival. The cohort will be established from colorectal cancer patients enrolled in two managed care organizations, Health Alliance Plan (Detroit, MI) and HealthPartners (Minneapolis, MN). Cohort subjects will be followed for at least five years for new evidence of disease, recurrence and survival outcome. Using automated pharmacy data, the timing of use and exposure to NSAIDs and HRT will be analyzed among cancer survivors, along with potentially confounding variables, in relation to these outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DECISION MAKING REGARDING HORMONE REPLACEMENT THERAPY Principal Investigator & Institution: Padonu, Georgia; None; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The career goal of this applicant is to develop the research skills to become an independent, externally funded biomedical researcher in the field of health decision making and achieve a record of research and publication productivity. The research focus is the development and testing of decision support interventions and their adaptability in the study of decision making regarding HRT among low income menopausal African American women. To accomplish the research career goals, the following objectives are developed for the proposed award period: 1. To expand knowledge of selected concepts, measurement and analytical strategies predominately used in decision support research development and testing. 2. To build on and expand skills in developing culturally sensitive research materials, instruments and interventions. 3. To increase knowledge of select conceptual frameworks used in decision making research to including both initial and continuance decision making, and with adaptability to low income African American women. 4. To increase theoretical knowledge of risk communication in the context of decision making research, issues of communication style, format preferences, with focus on application to low income, low literacy and diversity in study populations. 5. To maintain currency in clinical competency related to menopause and HRT with special interest in health risk assessment and quality of life as health status outcome. 6. To utilize knowledge and skills gained from career development activities to conduct pilot research of decision support for community-based low-income African American women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIET, HORMONE REPLACEMENT THERAPY AND BREAST CANCER Principal Investigator & Institution: Zhang, Shumin; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 12-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): This is a resubmission of I K07 CA096619-01 "Diet, Hormone Replacement Therapy and Breast Cancer". Candidate: Shumin Zhang received her MD at the Harbin Medical University in 1986 and her ScD in epidemiology and nutrition at the Harvard School of Public Health in 1998. She then completed her post-doctoral training in 2000, and now is an Assistant Professor of Medicine at the Harvard Medical School (HMS). She applies for this Career Development Award to acquire the methodological and theoretical research skills needed to become an independent scientist in cancer and nutritional epidemiology. Sponsor and Environment: JoAnn Manson, MD, DrPH, is the Chief of the Division of Preventive Medicine at the Brigham and Women's Hospital, Professor of Medicine at the HMS and Co Principal investigator (Co-Principal Investigator) of the Women's Health Study ONHS). Julie Buring, ScD, is the Deputy Director of the Division, Professor of Ambulatory Care and Prevention at the HMS and Principal Investigator of the WHS. They have trained numerous investigators in the fields of diet, lifestyle and chronic diseases, areas in which they have published extensively. Research: We plan to conduct a prospective analysis within the WHS, an ongoing clinical trial of vitamin E and lowdose aspirin in the primary prevention of cancer and cardiovascular disease among

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39,876 women. We will test 4 dietary hypotheses that moderate alcohol intake increases risk of breast cancer, whereas high intake of folate and fiber reduces risk; and caffeine intake is not associated with risk. We will link fiber intake to plasma endogenous sex steroid hormones in a subsample of the WHS. We will also test 4 hormone replacement therapy (HRT) hypotheses that tong-term use of estrogen plus progestin increases risk of breast cancer more than estrogen alone; estrogen plus cyclic progestin increases risk more than estrogen plus continuous progestin; low-dose estrogens confer lower risk than high-dose; and use of estrogen is more strongly associated with risk among women drinking alcohol. The ongoing WHS will provide updated and repeated measures of HRT, comprehensive dietary assessment at baseline, and important covariates for breast cancer in addition to follow-up of the cohort and documentation of breast cancer cases (expected N = 1550). The findings from this project could have direct clinical application for efforts to reduce risk of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF SOYBEANS ON BONE AND THE REPRODUCTIVE TRACT Principal Investigator & Institution: Bahr, Janice M.; Professor; Animal Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: (adapted from the applicant's abstract) Some postmenopausal women use hormone replacement therapy (HRT) to maintain bone. This treatment is, however, not acceptable to all women. An alternative approach is intake of foods rich in phytoestrogens - natural plant estrogens such as soybeans. The hypothesis is that soy protein protects against postmenopausal bone loss by slowing resorption and enhancing bone formation due to organ-selective estrogenic effects of the isoflavones genistein and daidzein. The applicant proposes four questions: 1. Efficacy: What is the effect of soy protein and soy isoflavones on bone formation and resorption? 2. Safety: Do soy isoflavones and estrogen have differential effects on bone and female reproductive tissues? 3. Safety: Do soy proteins or isoflavones antagonize the effects of endogenous estrogen on bone and the reproductive tract? 4. Mechanism: Do soy isoflavones differentially affect estrogen-dependent bone resorption and formation through estrogen receptor-mediated mechanisms? In vivo studies will use ovariectomized rats, an established model for osteoporosis, and intact rats. In vitro studies will use mouse calvarial explant culture and an estrogen receptor reporter system. To answer questions 1-3 ovariectomized and inteact rats will be fed diets of various concentrations of soy or isoflavones for 3 months. Measurements during and at termination of experiments are urinary deoxypyridine, an indicator of bone breakdown; bone mineral density; and bone formation by histomorphometry. The reproductive tract will be evaluated by histology and production of Complement C3 by the uterus and measurement of estradiol and luteinizing hormone in plasma. In vitro studies (question 4) will determine if isoflavones act through an ER and which subtypes, ERa or ERb. These studies are necessary to identify efficacious and safe alternative approaches to HRT readily accessible to all women. Knowledge of active agents and mechanism of action will allow standardization of soy supplements; identification of doses that maintain bone health without compromising other systems, e.g. reproductive; and assurance against interactions from like compounds in other drugs and food, including supplements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOGENOUS/EXOGENOUS SEX HORMONES & CHD RISK FACTORS Principal Investigator & Institution: Barrett-Connor, Elizabeth L.; Professor and Chair; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Coronary heart disease (CHD) is the most common cause of death in U.S. women. Observational studies consistently show that postmenopausal estrogen, with or without a progestin, reduces the risk of CHD, and there are several plausible mechanisms by which estrogen might protect the heart. Nevertheless, clinical trials to date have not demonstrated cardioprotection. If hormone levels play a role in determining CHD risk in postmenopausal women and HRT is to be used as a means of reducing that risk, the interactions of endogenous hormones, HRT, and CHD risk factors need further definition, in particular the effect of covariates. Individual characteristics such as basal hormone levels, body size, past hormone use, and lifestyle decisions may modify responses to HRT. This proposal focuses on four questions: 1) what factors determine circulating sex hormone levels in postmenopausal women, 2) what factors determine changes in sex hormone levels in response to hormone replacement therapy (HRT), 3) do endogenous sex hormone levels influence CHD risk factors in postmenopausal women, and 4) do changes in sex hormone levels with HRT predict the effect of HRT on CHD risk factors. These questions will be addressed by analyzing existing data from the Postmenopausal Estrogen / Progestin Interventions Trial (PEPI), a 3-year, multi-center, double-blind, placebo-controlled trial designed to compare the effect of estrogen alone and 3 estrogen/progestin HRT regimens vs placebo on selected CHD risk factors. There were 875 participants. Serum sex hormone levels, CHD risk factors, and potential covariates (including demographic characteristics, anthropometric measurements, reproductive history and lifestyle variables), determined at baseline and at 24 or 36 months of treatment, will be considered in the analyses. Results of this study will help define the differences between women with regard to endogenous sex hormone levels and responses to HRT, and the relation of sex hormones to CHD risk factors. These observations may aid in deciding whether individual women should use HRT and, if so, which regimen would provide the most benefit with the least risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF OVARIAN CANCER:NEW HYPOTHESES Principal Investigator & Institution: Rossing, Mary A.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Much of the previous epidemiologic research on ovarian cancer has been conducted within the conceptual with conceptual framework of the ovulation and gonadotropin. However, additional mechanisms must be operative to account for epidemiologic findings regarding this disease. In this study, we will address the hypothesis that progesterone reduces risk of epithelial ovarian cancer. We will examine the relation of exogenous progestins administered as a component of hormone replacement therapy (HRT) with disease risk. We will further assess whether sunlight and dietary sources of vitamin D influence risk. The study will contribute to a better understanding of pathogenic mechanisms of epithelial ovarian cancer, and may provide information leading to new means of reducing the occurrence of this disease. We

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propose to conduct a population-based, case-control study of epithelial ovarian cancer among women aged 35-74 years residing in thirteen counties of Washington State. Cases will be identified through a population-based cancer registry operating as part of the Surveillance, Epidemiology and End Results Program. Controls will be identified through random digit telephone dialing, and will be selected to be similar in age and area of residence to cases. In-person interviews will be conducted and blood samples will be collected. The findings of this study will have appreciable public health importance. Study of the impact of different HRT regimens, particularly estrogen/progestin combinations, on ovarian cancer risk has been deemed an urgent task for research. Recent calls for reappraisals of the risk/benefit ratio of unopposed estrogen and combined estrogen/progestin HRT highlight the need to understand the relation of these medications with ovarian cancer risk, and to incorporate this knowledge into risk/benefit considerations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF VENOUS THROMBOEMBOLISM Principal Investigator & Institution: Glynn, Robert J.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: Venous thromboembolism (VTE) is a common condition causing substantial morbidity, cost and mortality, yet several aspects of the epidemiology of this disease remain unexplored. The major aim of this proposal is to evaluate potentially modifiable lifestyle predictors of VTE and their joint associations with biochemical and genetic determinants. Studies will identify determinants of both initial occurrence of VTE as well as recurrence among persons with a prior event. The study design is a prospective cohort study of 77,118 persons based on pooling information from four large randomized trials of US health professionals that have collected detailed risk factor information and have used common strategies to prospectively identify and validate cases of VTE. These trials are: Physicians' Health Studies I and II including 29,071 US male physicians, of whom 22,071 have been followed since the initiation of the first trial in 1982; the Women's Health Study including 39,876 female health professionals who will have an average of 10 years of follow-up; and the Women's Antioxidant Cardiovascular Study including 8,171 female health professionals with prevalent cardiovascular disease or at high risk of cardiovascular disease who will have an average of 8 years of follow-up. Archived blood samples were collected from approximately 75 percent of participants at baseline and will be used to assess biochemical and genetic markers of risk including factor V Leiden, the G20210A mutation in the prothrombin gene, hyperhomocysteinemia, and anticardiolipin antibodies. The study will assess the joint association with risk of these markers and potentially modifiable factors including body mass index, hormone replacement therapy, physical activity, and aspirin use. The study population will include over 1,000 incident cases of VTE, including 750 with blood samples. The large size, prospective design, high follow-up rates, detailed and reliable long-term exposure and outcome information, and the availability of blood specimens on a large subgroup, combined with the relatively low cost, make these cohorts a valuable and unique resource for studying determinants of risk of VTE. The results of this work may lead to new strategies for VTE preventio. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF VENOUS THROMBOSIS AND PULMONARY EMBOLISM Principal Investigator & Institution: Folsom, Aaron R.; Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 31-DEC-2006 Summary: (provided by applicant): Venous thromboembolism (VTE), comprising deep venous thrombosis and pulmonary embolism, is a major contributor to morbidity and mortality in the US. We propose here a 4-year continuation of our unique and informative Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective study within the ARIC and CHS cohorts. We have several important findings from the previous project period, the three most important being (1) identification for the first time in a prospective study that plasma fibrin fragment Ddimer, a marker of fibrin turnover, is positively and strongly associated with risk of future VTE, (2) verification, again for the first time prospectively, that factor VIII and von Willebrand factor are strong risk factors for VTE, and (3) demonstration that obesity and diabetes are important VTE risk factors, but that most other arterial disease risk factors, including fibrinogen and C-reactive protein, are not. We plan to build upon these findings during LITE continuation, by adding new cases and testing new hypotheses. Our aims are 1. To extend VTE event follow-up in the LITE Study for 4 more years, which is expected to increase the current number of VTE events (n=335) by 47 percent (to n=493), and to sample 1 control per case. In the new cases and controls, we will measure analytes found to be important in LITE already (factor V Leiden, prothrombin G20210A variant, D-dimer, and TAFI), to serve as covariates in combined analyses. 2. To conduct nested case-control studies in the entire sample of 493 VTE cases and 828 controls, using prediagnosis blood and DNA specimens, to determine the prospective associations of VTE with several novel plasma hemostatic factors and genetic markers. 3. To conduct longitudinal analyses of VTE incidence and potential risk factors (or interaction) that we have not yet fully explored: diet, frailty, hormone replacement therapy, and obesity interactions. 4. To study serial blood levels of Ddimer and homocysteine, to better understand their associations with VTE occurrence. Continuation of this comprehensive prospective study will provide additional important epidemiologic insights into the etiology of VTE. This could lead to new strategies for prevention or treatment of VTE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN RECEPTOR VARIANCE AND CHD RISK IN HERS Principal Investigator & Institution: Herrington, David M.; Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-MAY-2005 Summary: (provided by applicant): Estrogen raises HDL cholesterol levels - an effect that may account for the favorable association between hormone replacement therapy (HRT) and coronary heart disease (CHD) risk in postmenopausal women. Several lines of evidence suggest that genetic factors also influence HDL levels, although the precise genes involved have not yet been determined. Recent evidence from the Estrogen Replacement and Atherosclerosis (ERA) trial (N = 309) indicates that certain allelic variants in the estrogen receptor-alpha (ER-alpha) gene are associated with more than a twofold increase in estrogen's effects on HDL cholesterol. Women with the favorable genotype (ca. 20% of women) experienced a 26% increase in HDL with HRT compared with a 13% increase observed in the remaining women. However, this trial was too

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small to determine if these effects translate into an angiographic or clinical benefit. The Heart and Estrogen Replacement Study (HERS) was a large (N = 2763) randomized clinical endpoint trial of HRT for secondary prevention of CHD. This clinical trial cohort provides an ideal opportunity to confirm or refute the associations and interactions observed in the ERA trial with respect to lipids, and extend these observations to other estrogen-sensitive intermediate endpoints and clinical disease outcomes. Therefore, we propose to genotype HERS women with respect to several ER-alpha polymorphisms, and to examine the relationship between these ER-alpha genotypes, HRT use, change in HDL, and risk for CHD events. We will also examine the effects of ER-alpha polymorphisms on other plasma lipids, C-reactive protein, bone mineral density, risk for venous thromboembolic events, stroke, fractures, and all-cause mortality. Use of data and specimens from HERS is an efficient means to study the clinical impact of ER-alpha polymorphisms and possible modulation of estrogen action. If there are common polymorphisms in the ER-alpha gene that modify estrogen's effects on HDL and possibly other domains of estrogen action, this information could improve patients' and clinicians' ability to assess risks and benefits of HRT use. In addition, this information could lead to fundamentally important new knowledge about mechanisms of estrogen action, regulation of HDL cholesterol, and pathogenesis of CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN REGULATED GENES AND NEURAL PROTECTION Principal Investigator & Institution: Sisk, Cheryl L.; Professor and Director; Microbiology and Public Health; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2002 Summary: Epidemiological studies indicate 6that estrogen hormone replacement therapy in postmenopausal women reduces the risk of Alzheimer's Disease. One mechanisms by which estrogen may reduce risk of Alzheimer's Disease is inhibition of beta-amyloid plaque formation and ensuing cell death in hippocampus and cortex, which are among the most severely affected brain regions in Alzheimer's Disease. Using cDNA array assays to screen for estrogen-regulated genes in a mouse model of menopause, three genes were identified that are both regulated by estrogen in the hippocampus and frontal cortex and are known to be involved in amyloid precursor protein (APP) processing, plaque formation, and apoptosis. These genes encode transthyretin precursor (TTR), presenilin 1 (PS1), and presenilin 2 (PS2). Presenilins promote neural degeneration by cleaving APP into plaque-forming beta-amyloid peptide fragments (Abeta42) and inducing apoptosis. In contrast, TTR impedes plaque formation by sequestering Abeta42. The cDNA array data suggest two novel mechanisms for neural protection by estrogen: 1) inhibition of PS1 and PS2 gene expression, and 2) stimulation of TTR gene expression. The goal of the proposed project is to confirm and extend the findings based on cDNA arrays. The Specific Aims are to 1) confirm and precisely quantify estrogen regulation of TTR, PS1, and PS2 mRNA and protein are regulated by estrogen using in situ hybridization histochemistry and immunocytochemistry. The proposed studies employed a newly developed in vivo mouse model of menopause in which tissue responses to estrogen are assessed and compared when hormone replacement therapy is begin in either early or late menopause. The long-term goal of this work is to contribute to the development of hormone replacement strategies for post-menopausal women that are optimally effective in delaying or preventing the progression of Alzheimer's Disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN, ANGINA, ACTIVITY AND QUALITY OF LIFE IN WOMEN Principal Investigator & Institution: Missik, Eugeria; None; Kent State University at Kent Research & Graduate Studies Kent, Oh 44242 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: Postmenopausal women comprise the largest number of female cardiac patients. Recently recognized vasoactive effects of estrogen have shown to improve coronary blood flow in postmenopausal cardiac women especially during exercise. Our recent pilot study conducted on 37 postmenopausal cardiac women identified some notable trends between women receiving hormone replacement therapy (HRT) and those women not receiving HRT. Women on HRT performed activities of higher intensity for longer periods of time, reported lower severity of angina, and higher quality of life. Studies on the relationship of hormonal status and daily physical activity of cardiac patients are not available. To what extent estrogen replacement therapy (ERT) impacts the daily physical activity of postmenopausal cardiac patients is not known. It is hypothesized that the antischemic effects of estrogen positively impact daily physical activity and quality of life of postmenopausal cardiac women. Therefore, the primary aim of this study is to test a model examining the relationship between ERT use and frequency and severity of angina, daily physical activity, and quality of life. A prospective, comparative and cohort study will be used. Data will be collected on 180 postmenopausal cardiac women at three hospital based cardiac rehabilitation centers in western Pennsylvania. Multiple measures will be used for each construct in the model. Physical activity will be measured by self-report and electronic monitoring using the Tri Trac R3D accelerometer. Angina will be measured by the supplemented Rose Questionnaire, frequency by self-report, and severity by a numerical scale. Quality of life will be measured by using the Medical Outcomes Study, Short Form 36-Items. Structural equation analysis will be used to model the impact of ERT on the dependent variables. A demonstrated positive impact on physical activity may provide an additional rationale for the prudent use of ERT in the optimum management of postmenopausal cardiac patients. Interventions to support the adoption and maintenance of physical activity recommendations by postmenopausal cardiac women are greatly needed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN, CYTOKINES AND HEART FAILURE IN WOMEN Principal Investigator & Institution: Reis, Steven E.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 10-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): Congestive heart failure (CHF) is a leading cause of morbidity, mortality, and hospitalization in women. The observation that women with nonischemic cardiomyopathy have an age-related increase in mortality suggests that postmenopausal estrogen loss may alter the phenotypic expression of CHF. Because estrogen is a potent in vitro inhibitor of pro-inflammatory cytokines (e.g., TNFa, IL-1B, IL-6), which are re-expressed by the failing myocardium in patients with CHF and are related to an adverse prognosis, we postulate that estrogen replacement will improve the outcome of postmenopausal women with CHF. This hypothesis is supported by our preliminary data that demonstrate 1) female sex confers a survival advantage in transgenic mice with CHF due to over-expression of TNFa, 2) female sex is associated with an attenuated pathologic response of cardiac myocytes to TNFa, 3) estrogen and

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progesterone inhibit TNFa production by rat cardiac myocytes, 4) estrogen replacement therapy in postmenopausal women with CHF abrogates an age-related increase in TNFa, and 5) estrogen therapy in women with severe CHF is associated with a significant decrease in mortality. Our proposed randomized placebo-controlled doubleblind study of hormone replacement therapy in women with CHF will evaluate the hypothesis that estrogen has a protective effect in postmenopausal women with CHF related to modulation of TNFa and associated "downstream" cytokines (i.e., IL-lB. IL-6) and/or myocardial expression of cytokine receptors. We plan to compare the effects of hormones on functional capacity, biventricular mass and function, and quality of life with their effects on circulating cytokines in postmenopausal women with CHF. To determine the degree of hormone-induced cytokine suppression that is associated with favorable outcome, we will compare post-treatment cytokine levels in women with CHF with cytokine levels in a "control" group of women from the NHLBI WISE study who have no evidence of CHF and normal ventricular function. The results of this study will define the mechanism of estrogen's beneficial effect in postmenopausal women with CHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN/PLATELET INTERACTION IN CEREBRAL ISCHEMIA Principal Investigator & Institution: Kearney, Marguerite L.; Associate Professor; Anesthesiology/Crit Care Med; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: Platelet activation in the cerebrovasculature has been implicated as a mediator of tissue injury following stroke or other ischemic events. Data suggest that pre-menopausal women are at lower risk than men for cardiovascular diseases including stroke and transient ischemic attacks, conceivably due to the effects of estrogenic hormones on platelet biology or vascular function. Many women make a choice to receive hormone replacement therapy, but controversy surrounds the risks versus the benefits of estrogen therapy. Recent studies indicate that increasing estrogen levels promotes expression of the antiaggregant vasodilator, nitric oxide (NO), while depressing platelet elaboration of the adhesion molecule, P-selectin. We propose to study the effects of elevated estrogen on platelet biology to determine if the hormone moderates alterations in pre and post-ischemic platelet function or microvascular vasodilator capacity via the expression of vasoconstrictive platelet products. In Aim 1 we will determine if chronic estrogen in two physiologic doses modulates platelet biologic via a P-selectin mediated mechanism at baseline or after global cerebral ischemia. In Aim 2 we will test if chronic estrogen in two physiologic doses modulates changes in post-ischemia pial vessel vasodilatory capacity via attenuation of the release of adhesive or vasoactive platelet products. In Aim 3 we study the interrelationship between NO and P-selectin expression. We will determine, if the effects of chronic estrogen treatment in two physiologic doses improves microvascular perfusion by depressing post-ischemic platelet and endothelial P-selectin as a result of increased nitric oxide production. We will use whole blood platelet aggregometry, intravital microscopy, immunological and biochemical techniques to ascertain how estrogen affects platelet biology and microvascular endothelial function. The studies proposed in this project will clarify the contribution of exogenous estrogen therapy in ischemic brain injury both mechanistically and according to dosage. These are important considerations which impact nursing therapeutics given the controversy surrounding the safety and efficacy of estrogen replacement regimens.

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Project Title: FACTORS AFFECTING SURVIVAL OF YOUNG CANCER PATIENTS Principal Investigator & Institution: Malone, Kathleen E.; Associate Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 05-JUN-1993; Project End 30-APR-2003 Summary: This application for a competitive renewal of "Factors that affec survival of young breast cancer patients", seeks to extend for five more years the follow-up for recurrence and mortality of a population-based cohort of 128 women who were diagnosed with invasive breast cancer before age 45 during the years 1983 through 1992. These women provide the investigators with a unique opportunity to investigate the interrelationships between epidemiologic risk factor data, tumor characteristics, and breast cancer occurrence and/or mortality in a population-based setting where all cases of breast cancer in a defined geographic area could be assessed, eliminating potential biases impose by studies at referral centers or clinical trials, where women may selfselect into the study and not be representative of women in general who get breast cancer. During the past five years, this cohort was followed through follow-up questionnaires and hospital chart reviews, and their tumor specimens were tested for characteristics related to aggressiveness and prognosis. It is important to extend followup of this cohort to a minimum of ten years since patient and tumor characteristics may have different relationships with short and long-term mortality. During the next five years, the investigators propose to (a) expand data collection and specimen analyses to the entire cohort (rather than the subgroup of 930 they originally proposed), (b) extend the minimum follow-up period for the entire cohort to ten years, (c) collect updated information on recurrences, treatment, the use of hormone replacement therapy and childbearing after diagnosis, (d) add apoptotic index to the laboratory analyses, and (e) conduct comprehensive analyses of all of these data in relation to mortality and diseasefree survival. Young women with many years of potential life to lose who do not fall into clear prognostic categories present a major challenge to clinicians. By gainin an understanding of the association between epidemiologic risk factors and tumor characteristics related to aggressiveness as well as actual risk of recurrence or death, it is possible to develop profiles of women at high risk for aggressive tumors who might benefit from aggressive treatment and of those with low risk tumors for whom such aggressive treatment may not be necessary. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FT-IR OSTEOPOROSIS

MICROSCOPY

OF

MINERAL

STRUCTURE

IN

Principal Investigator & Institution: Boskey, Adele L.; Starr Chair in Mineralized Tissues; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-JUL-2005 Summary: (provided by applicant): Osteoporosis is estimated to affect 15-20 million people (both women and men) each year, causing significant morbidity and mortality. The widely used predictors of fracture risk are bone mineral density (BMD) and incidence of a previous fracture. One of the dilemmas in the management of osteoporosis is that two individuals with the same bone density and similar life-styles can show extensive diversity in their tendency to fracture. There is little information on what, other than differences in life style and fall severity, can account for this discrepancy. The underlying hypothesis of this grant is that discrete differences in

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mineral and matrix properties contribute to the altered fracture risk in these individuals. Over the past two funding periods, we have shown that Fourier transform infrared microspectroscopy (FTIRM) and imaging (FTIRI) provide reproducible and valuable information on the mineral and matrix properties of bone. We now wish to extend this approach to two new research questions: Aim 1) Do the mineral and matrix properties differ in biopsies from patients with fracture compared with patients without fractures while controlling for age, gender, bone mineral density, and architecture? This question will be tested by assessing biopsied specimens from individuals with different fracture histories and with known age, gender, and bone mineral density. MicroCT will be used to assess architecture of the specimens, and FTIR will be used to characterize mineral and matrix properties. Under this specific aim, we will also examine associations between FTIR parameters and nanoindentation in a subset of biopsies to establish the nanoindentation technique and to test for significant correlations between mineral/matrix properties and indentation modulus and hardness. We will also develop the use of imaging ATR to establish an IR approach that does not required thin sections of embedded bone. Aim 2) Do therapeutic agents reverse the observed alterations in mineral and matrix properties? Specifically we shall examine the relative effects of a SERM (selective estrogen receptor modulator), raloxifene, Hormone Replacement Therapy, and a bisphosphonate (Risedronate) on the mineral and matrix properties in pre- and post- therapy biopsies, to identify the agent(s) that reverse(s) the observed alterations in mineral and matrix properties. Emphasis will be placed on those properties identified in Aim 1 that are most predictive of fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAPENTIN VS ESTROGEN FOR THE TREATMENT OF HOT FLUSHES Principal Investigator & Institution: Reddy, Sireesha; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Hot flashes and other climacteric symptoms affect 75% of postmenopausal women in the US and are associated with higher rates of depression and sleep disturbance. Although hormone replacement therapy (HRT) is highly effective in reducing hot flashes, there is concern that HRT is associated with an increased risk of thrombo-embolic events, breast cancer and ovarian cancer. In addition, it is poorly tolerated in clinical practice, with about 30% of women discontinuing therapy after a mean of 4.5 months. Many other women have a contraindication to HRT, such as a history of an estrogen-sensitive tumor, liver dysfunction, or a hypercoagulable state. Safe, effective, and well-tolerated alternative therapies for hot flashes are needed. Gabapentin is a gamma-aminobutyric acid (GABA)-analog approved in 1994 for the treatment of seizures. Since then, it has been shown that gabapentin is efficacious for numerous off-label indications such as neuropathic pain, anxiety, bipolar disorder, and migraine headaches. The investigators have reported that gabapentin is associated with a reduction in the frequency of hot flashes in an uncontrolled series of postmenopausal women who were taking gabapentin for other indications. The investigators also report here preliminary data from a randomized, placebo-controlled trial showing that lowdose gabapentin was associated with a greater reduction in hot flash frequency than placebo after 12 weeks of treatment. However, it is not known whether the efficacy of gabapentin in the treatment of hot flashes and other menopausal symptoms is comparable to that of estrogen, the gold standard. A randomized trial of gabapentin, estrogen and placebo is needed to inform clinicians as to whether gabapentin is an

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effective alternative to estrogen. The first major aim of this proposal is to assess the screening and recruitment of menopausal women into a randomized trial of gabapentin, estrogen and placebo in the treatment of climacteric symptoms. The second major aim is to obtain preliminary estimates of the frequency and severity of climacteric symptoms among women receiving gabapentin, estrogen and placebo. Pilot data from these two aims will permit estimates of sample-size requirements for a full-scale randomized trial, and of the overall feasibility and cost of such a trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER AND MENOPAUSE ON NUTRIENT AND ENERGY METABOLISM Principal Investigator & Institution: Horton, Tracy J.; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2004 Summary: The overall aim of the P.I.'s research is to better understand gender differences in energy and nutrient metabolism that related to the development and/or protection against disease. The health risks associated with a number of diseases including obesity and coronary heart disease are different between males and females. Knowledge of gender differences in energy and nutrient metabolism are required to fully understand the metabolic basis of these diseases. Studies in this proposal will begin to determine gender specific aspects of energy and nutrient metabolism and how these change at menopause. Specific aim number 1 will be to determine the sources of carbohydrate and lipid fuels utilized during exercise in males and females. This will be determined using indirect calorimetry and stable isotope techniques and muscle biopsies. Specific aim number 2 will be to determine the lipolytic response to catecholamines in males and females by using the pancreatic clamp technique in conjunction with catecholamine infusions and stable isotope measurements. Specific aim number 3 will be to determine whether males and females differ in their ability to remove exogenous lipid from the circulation and whether there are gender differences in the ability of insulin to suppress endogenous very-low density lipoprotein triglyceride (VLDL-TG) production. Triglyceride removal will be assessed in response to an intravenous fat tolerance test. Relative changes in VLDL-TG production will be measured following the radioactive labeling of VLDL-TG and measurement of VLDLTG kinetics under basal and hyperinsulinemic/euglycemic conditions. Specific aim number 4 will be to determine the effect of menopause and hormone replacement therapy on energy expenditure and resting substrate utilization. Free-living energy expenditure will be measured using the doubly labelled water technique and substrate utilization will be assessed using indirect calorimetry and stable isotope techniques. These studies will further our understanding of the metabolic basis for disease risk in males and females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENDER, SEX STEROIDS AND DRY EYE SYNDROMES Principal Investigator & Institution: Sullivan, David A.; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-1985; Project End 30-NOV-2006 Summary: (provided by applicant): The preocular tear film plays a critical role in maintaining ocular surface integrity, protecting against microbial challenge and preserving visual acuity. Tear film dysfunction, in turn, may severely impact the eye

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and lead to desiccation of the corneal epithelium, ulceration and perforation of the cornea, an increased incidence of infectious disease, and pronounced visual impairment and blindness. Countless people suffer from tear film disorders, which are termed dry eye syndromes and are classified into 2 major types: aqueous-deficient and evaporative. Aqueous-deficient dry eye is due to decreased tear secretion from the lacrimal gland. An example is Sjogren's syndrome, a common autoimmune disease that afflicts primarily women and destroys the lacrimal gland. Evaporative dry eye is typically caused by meibomian gland dysfunction and may be a major cause of dry eye during menopause, use of estrogen hormone replacement therapy (HRT) and aging. The long range objectives of this grant application are to test our hypotheses that: (1) sex steroids are extremely important in the physiological regulation of the lacrimal and meibomian glands, as well as the production of the tear film; and (2) gender, sex steroid hormones, and in particular androgen deficiency, are critical etiologic factors in the pathogenesis of both aqueous-deficient and evaporative dry eye syndromes. Experimental procedures include mouse models, DNA hybridization arrays (i.e. gene chips), RT-PCR, ribonuclease protection assays, Northern, slot and Southern blots, in situ hybridization, cell cultures, immunoassays, HPLC/mass spectrometry, enzyme assays, histology, image analysis, hormone reconstitution experiments, as well as clinical studies with humans. Our specific aims are to: (1) identify the genes and proteins that mediate the gender-related differences in, and the sex steroid control of, lacrimal glands in normal and autoimmune (i.e. Sjogren's syndrome) mice; (2) identify the genes and proteins involved in the gender-associated variations in, and the sex steroid regulation of, the mouse meibomian gland; and (3) determine the specific effects of HRT use (estrogen, or estrogen plus progesterone), with or without androgen supplementation, on the ocular surface of postmenopausal women. Results from the studies should significantly advance our understanding of the processes by which gender and sex steroids influence the anterior segment of the eye. In addition, findings may have health relatedness for the eye, because they: (1) explore the regulation of the tear film; and (2) may lead to the development of specific therapies for the clinical treatment of dry eye syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES AND THE ESTROGEN EFFECT ON ENDOMETRIAL CANCER Principal Investigator & Institution: Ross, Ronald K.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The etiology of endometrial cancer is relatively well understood. Estrogen stimulation of the endometrium without the modulatory effects of progestins is the major cause. Estrogen replacement therapy (ERT) in menopause and obesity are the principal risk factors. The effect of the latter is probably due to the association between postmenopausal obesity and circulating bioavailable estrogen levels. Oral contraceptives and pregnancy, both of which deliver estrogen stimulation to the endometrium but with the continuous modulatory influence of progestins, are associated with reduction in risk. Combination hormone replacement therapy in which a progestin is added to estrogen for all or part of the monthly cycle results in no increase in endometrial cancer risk over that of a non-user of hormone replacement. Despite the fact that ERT and obesity are the major risk factors, only a small proportion of women using ERT or even with extreme obesity will develop endometrial cancer. It would be important from a public health as well as from a mechanistic view to be able to predict which women those will be. We propose to evaluate a series of eight candidate genes

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(CYP17, CYP19, HSD17B1, ER, CYP1A1, CYP1B1, COMT andPR) in the estrogen biosynthesis, transactivation and metabolism pathways to determine if the effects of these risk factors might be mediated or modified by genetic variability. We will evaluate this question in the context of a prospective epidemiologic study of 133,000 female California teachers (the California Teachers Study) using a nested case-control design. We will also examine in detail the possible impact of phytoestrogens on endometrial cancer risk reduction in conjunction with HRT, obesity and the eight candidate genes under evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC EPIDEMIOLOGY OF BREAST CANCER--BRCA1 AND BRCA2 Principal Investigator & Institution: Neuhausen, Susan L.; Professor; Medical Informatics; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2003 Summary: (Adapted from the Investigator's Abstract) Many environmental, reproductive, and genetic factors have been associated with an increased risk of breast and ovarian cancers. A family history of breast cancer has been identified as a major risk factor for the development of the disease. A genetic predisposition likely accounts for 5 to 10 percent of breast cancer and ovarian cancer. Approximately 80 percent of inherited early onset breast cancer is attributed to the breast cancer genes, BRCA1 and BRCA2. Among families with the same BRCA1 (BRCA2) mutations, there are differences in agespecific penetrance, lifetime penetrance, proportions of breast and ovarian cancer, and risks of other cancers. This variability suggests there are environmental and genetic factors interacting with the BRCA1 and BRCA2 genes. The identification of predictors of phenotypic expression, not only in terms of type of cancer but also in modulating age at onset, has implications for screening and prevention strategies for women at significantly increased risk of breast and ovarian cancers due to the BRCA1 and BRCA2 genes. This is a proposal to examine the effects of reproductive and genetic factors which may modulate the incidence by age and overall incidence of breast and ovarian cancers in individuals with BRCA1 and BRCA2 mutations. The cohort is composed of Caucasian and African American BRCA1 and BRCA2 mutation carriers. We have already sampled 215 BRCA1 and 141 BRCA2 mutations carriers in our Utah kindreds and will continue to sample within these families to identify all mutation carriers. Little information is available regarding prevalence of BRCA1 and BRCA2 in African Americans, although for women less than 44 years of age, their incidence of breast cancer is higher than for Caucasians. With collaborators in Dallas and Chicago, we propose to contact African American families with a history of breast and/or ovarian cancer, to identify BRCA1 and BRCA2 mutations, and sample within those families to identify all mutations carriers. The cofactors to be examined in this cohort include ages at menarche and menopause, parity, age at first pregnancy, use of oral contraceptives, and hormone replacement therapy. The genetic factors to be investigated include the hRAS VNTR and carcinogen metabolizing genes GSTT1, GSTM1, CYP2D6, CYP1A1, and EPHX. Survival analysis models will be used to estimate cumulative incidence by age and overall incidence for breast and ovarian cancers stratified by the hormone, reproductive, and genetic factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEART HEMODYNAMICS

DISEASE

IN

WOMEN:

ESTROGEN

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EFFECTS

ON

Principal Investigator & Institution: Sherwood, Andrew; Associate Professor; None; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 30-APR-2004 Summary: Coronary heart disease (CHD) has now become the leading cause of death in women. The incidence of CHD increases sharply following menopause, while estrogen levels decline. Data from observational studies suggest that higher estrogen levels may protect women from developing CHD. There is also evidence that estrogen may protect women who already have CHD. However, the cardioprotective benefits of estrogen alone may be countered by the addition of progesterone, which is typically included in hormone replacement therapy (HRT). The Heart and Estrogen/Progestin Replacement Study (HERS) recently reported that progesterone-estrogen combination therapy did not protect women with CHD from myocardial infarction and/or death. The mechanisms responsible for estrogen's cardioprotective benefits have not been fully identified. Estrogen replacement improves lipid profiles, but this mechanism alone accounts for only approximately 25 percent of the reduction in risk for mortality. Recent studies have shown that estrogen also appears to improve vascular endothelial function, which is compromised in CHD. Endothelial dysfunction simultaneously reduces myocardial oxygen supply by limiting coronary vasodilation, while increasing demand by elevating systemic vascular resistance. Depending upon the severity of this imbalance, CHD patients may experience myocardial ischemia, myocardial infarction and/or cardiac death. Several studies have shown that stress may exacerbate this pathophysiological imbalance in CHD and trigger acute events. The purpose of the proposed research is to further our understanding of estrogen and estrogen/progesterone's effects on endothelial function and its consequent impact on SVR at rest and during stress. In a randomized double-blind crossover comparison of 60 women with documented CHD and 60 age-matched healthy women, we propose to examine the acute effects of estrogen and estrogen/progesterone interventions on SVR at rest and during stress. Vascular endothelial function will be assessed using ultrasound imaging of flowmediated dilation of the brachial artery. Using recently developed ambulatory monitoring technology, blood pressure, cardiac output and SVR will be monitored noninvasively at rest, during laboratory-based mental stress, and for 24 hours during patients' normal daily routines. By these methods, the proposed research should clarify how HRT may alter risk in CHD through hemodynamic effects that are hypothesized to be secondary to alterations in endothelial function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HISTORY OF HORMONE REPLACEMENT THERAPY, 1960-2000 Principal Investigator & Institution: Watkins, Elizabeth S.; Individual Award--Watkins, Elizabeth Sie 6516 Northumberland St Pittsburgh, Pa 15217 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The goal of this project is to produce the first sociocultural historical study of the changing rationales for prescribing hormone replacement therapy (HRT) for menopausal and post-menopausal women from the 1960s to the present. The resulting book will provide a historical perspective for contemporary debates about the health care and health policy implications of menopause, aging, and HRT. The study is driven by three main questions. 1) How and where do physicians and patients get their information about menopause, aging, and

32


medical treatments? This project investigates the interactions among scientists, physicians, drug companies, government agencies, feminist health activists, the media, and the public in the construction, dissemination, and translation of medical information for midlife and older women. 2) In what ways have the phenomena of menopause and aging been both medicalized and de-medicalized? While menopause and its sequence, like other aspects of women's health (e.g., childbirth, birth control), have increasingly come under medical control in the 20th century, there has also been a parallel trend in recent decades to re-define menopause as a "natural" event. This project will analyze the differences and similarities between these two views and set them in the larger context of health policy making and the American pursuit of health. 3) What is the relationship between the medical treatment of menopause and cultural conceptions of aging? This project locates the use of HRT in the context of changing expectations and changing roles for older women in American society. Using historical methodologies to investigate the variety of actors engaged in disseminating information about menopause, aging, and medical treatment, this study will enrich our understanding of the practices, contexts, and meanings of aging and related health-care issues among American women. The primary product will be a book written for a broad audience, including historians, health policy makers, physicians, nurses, other health care providers, and the general public. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIV: GENDER AND SEX HORMONE EFFECTS ON T CELL KINETICS Principal Investigator & Institution: Hellerstein, Marc K.; Professor of Medicine; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2001; Project Start 23-APR-2001; Project End 31-MAR-2006 Summary: (Abstract Provided by Applicant) Gender differences have been documented for many aspects of immune function and are likely mediated by the major reproductive hormones (androgens, estrogens and progesterone). Gender differences in the natural history of human immunodeficiency virus-type 1 (HIV-l) infection have also been described. In particular, a different relationship between HIV-1 viral load (VL) and progression of disease has been reported for women as compared to men. The in vivo effects of gender or reproductive hormones on proliferation and survival of T cells, including thymic production of T cells, in the setting of HIV- 1 infection have not been directly tested, however. The objectives of our proposed studies are to compare the natural history of T cell turnover in men and women with early HIV-1 disease and to establish the consequences of sex steroids on T cell turnover, including thymopoiesis, in HIV-l infection. These studies are now possible in humans because of the recent development of stable isotope-mass spectrometric techniques for directly measuring the kinetics of purified T cell subpopulations in vivo. Three clinical studies will be performed. Study #1 will compare the natural history of CD4+ and CD8+ T cell kinetics in untreated, CD4-matched men and women with early HIV-l infection (CD4 counts 500-750 cells/uL; n~l5 per group). T cell kinetics will be measured by two complementary techniques ([6,6-2H2] glucose incorporation and die-away curves, to characterize memory/effector-phenotype T cell dynamics; long term 2H2O incorporation, to characterize kinetics of naive-phenotype T cells) at baseline then every 12-18 months over a 3-4 year follow-up. Correlation between VL, CD4 count, thymic mass (by CT scan), excision circles, and blood measurements (cytokines, hormones) will be compared in men and women. Our hypothesis is that chances in T cell kinetics will track with CD4 count in both genders, but at a lower VL in women. Study #2 will

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compare the effects of puberty in HIV-1 infected pre-adolescent boys and girls (n=8 per group). The outpatient 2H2O approach will be used to measure T cell dynamics. Other parameters will be correlated as in study #1. The central hypothesis is that the rise in sex steroids will suppress thymopoiesis in both genders. perhaps greater affecting boys. Study #3 will compare the effects of reproductive hormone replacement therapy in hypogonadal adult men and women with HIV-1 infection (n=8 per group). The 2H2O method for measuring T cell dynamics will be used. with other measurements as in Studies I and 2. The hypothesis is that sex steroids will reduce production of naivephenotype T cells in both men and women, with perhaps a greater effect in men. In summary, we propose to determine directly, in vivo, whether sex steroids alter T cell kinetics (particularly thymopoiesis) in HIV-1 infected humans. and whether T cell turnover tracks better with CD4 count than VL in women, compared to men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL INFLUENCES ON COGNITION Principal Investigator & Institution: Luine, Victoria N.; Professor; Hunter College 695 Park Ave New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: A variety of studies show that estrogen may promote memory in females, both animal and human with low estrogen levels. Moreover, estrogen may also delay or prevent the onset of Alzheimer's Disease and improve cognition in women with the disease. Using young and aged rats as models, experiments will examine effects of gonadal hormones on memory using a spatial memory task, object recognition. First, the dose- response relationship between estrogen and enhanced memory will be determined. Whether concurrent administration of progesterone with estrogen alters the enhancing effects of estrogen on memory will be tested. Then possible enduring effects of gonadal hormones on memory will be tested, i.e., whether chronic estrogen alone or with progesterone enhances memory months after discontinuation. Effects of these hormone treatments on GABAergic and monoaminergic neurotransmission in brain areas involved in memory function will be measured by neurochemical techniques. Whether alterations in memory occur over the estrus cycle and after chronic ovariectomy will be determined and will show whether hormones exert short term effects or long term, trophic effects. Thus, proposed experiments will characterized fundamental relationships between gonadal hormones and memory function. While important for providing basic information concerning hormone actions and the neural bases for hormonal effects on memory, the studies also have significant health implications for aging and Alzheimer's disease. Concurrent estrogen and progesterone therapy is the treatment of choice for post menopausal women, but little is known about the effects of progesterone on memory. In addition, if post-menopausal hormone replacement therapy can delay dementia onset by 5 years, the incidence of dementia has been projected to decreased by 50%. Finally, if only a few years of replacement can be given with the same benefits on memory loss or in developing AD, then the risk of side effects of estrogen can be greatly minimized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT AND AGING EFFECTS ON MEMORY Principal Investigator & Institution: Wegesin, Domonick J.; Assistant Professor of Neuropsychology; Sergiersky Center; Columbia University Health Sciences New York, Ny 10032

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Timing: Fiscal Year 2001; Project Start 17-DEC-1998; Project End 30-NOV-2003 Summary: Memory loss is one of the main complaints of normal aging. Recent evidence suggests that hormonal changes accompanying menopause may partly account for memory-loss in aging women and that these memory effects can be tempered by the use of hormone replacement therapy (HRT) (Sherwin, 1994). The mechanism of these cognitive benefits remains unclear. The overall objective of this research is to delineate better the effects of HRT on memory in post-menopausal women. Previous studies of HRT have limited their assessment of memory to clinical measures focusing almost exclusively on recall ability. The proposed studies will extend our current understanding of HRT-mediated memory effects by examining multiple types of human memory within controlled experimental paradigms. In addition to examining the effects of HRT on memory, the proposed studies will also investigate normal age-associated memory impairment. Specifically, healthy postmenopausal women drawn from a representative community sample who have undergone long-term HRT and agematched controls who have never used HRT will be compared to younger premenopausal women on tests of implicit memory (priming) and explicit memory (recalling and recognition) for verbal and non-verbal material. Beyond proving a better description of the behavioral effects of HRT, we are interested in examining potential neural mechanisms by which estrogens modulate memory function. Specifically, we are interested in dissociating memory mediated by the frontal and medial temporal lobes. To that end, event-related brain potentials (ERPs) will be recorded from 64 scalp sites during the experimental tasks in an attempt to elucidate the electrophysiological indices of HRT-related memory enhancement. Overall, this work will serve as a mens to better elucidate the type of memory changes associated with HRT and to provide an initial examination of brain-behavior associations related to the memory effects reported in HRT-using postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE CARDIOVASCULAR RISK

REPLACEMENT

AND

METABOLIC

Principal Investigator & Institution: Sites, Cynthia K.; Obstetrics and Gynecology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 02-DEC-1998; Project End 30-NOV-2003 Summary: The menopause transition is associated with a pronounced increase in risk of cardiovascular disease. Hormone replacement therapy in postmenopausal women reduces the risk of cardiovascular disease by approximately 50 percent, although the mechanisms involved are poorly understood. We will examine the impact of hormone replacement therapy on metabolic risk factors affecting cardiovascular disease and future health in aging women. Our overall hypothesis is that hormone replacement therapy in the early postmenopausal period reduces the central accumulation of body fat and improves insulin sensitivity, thereby reducing a metabolic risk factor for cardiovascular disease. A total of 88 women will be recruited for this 2-year randomized double-blinded placebo-controlled longitudinal study. We will measure outcomes of changes in body fat distribution and insulin sensitivity on 4 occasions (baseline, 6 months, 1 year and 2 years) in women taking continuous conjugated estrogens plus medroxyprogesterone acetate or placebo. Our study will provide new information on the temporal sequence of changes in outcome variables. We will use: 1) computerized tomography (CT) and dual photon x- ray absorptiometry (DEXA) scanning to measure intra-abdominal body fat and total body fat, and 2) euglycemic clamps to measure insulin sensitivity. Analysis of these data will provide an understanding of the impact of

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hormone replacement on the syndrome of central obesity and insulin resistance, which predisposes women to increased risk for cardiovascular disease. In addition, our study may allow physicians to target hormone replacement to women with specific body compositions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT FOR PREVENTION OF VISCERAL OBESITY Principal Investigator & Institution: Cefalu, William T.; Associate Professor of Medicine; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 31-AUG-2003 Summary: The goal of this study is to determine the therapeutic role of hormone replacement therapy (HRT) to prevent visceral obesity in postmenopausal women. The hypothesis is that HRT will augment the loss of visceral fat in postmenopausal women who undergo a 6-month weight reduction program, and that HRT will be useful in preventing visceral fat regain in women who continue HRT after a one-year follow-up. In addition, the study will examine whether changes in visceral fat are predictive of alterations in insulin sensitivity. postmenopausal women with abdominal obesity will be randomly assigned to either HRT or placebo intervention. All women will participate in a 6-month program of exercise and dietary restriction designed to induce a moderate fat loss. Women will be re-examined after a one-year follow-up period. Total abdominal and visceral fat will be measured with CT, body composition with DXA, insulin sensitivity with an euglycemic/hyperinsulinemic clamp, and energy balance with indirect calorimetry and doubly-labeled water before and after the weight reduction program, and after the one-year follow-up. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT IN MENOPAUSAL WOMEN WITH EPILEPSY Principal Investigator & Institution: Harden, Cynthia L.; Neurology and Neuroscience; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 30-APR-2003 Summary: (Applicant's Abstract): The long-term objective is this study is to determine whether standard hormone replacement therapy is safe for menopausal women with epilepsy. The benefits of hormone replacement therapy for menopausal women are becoming widely appreciated. It is expected that hormone replacement therapy will be increasingly prescribed in a portion of the American population that is also increasing in number. Therefore, the safety of hormone replacement therapy in the settings of specific illnesses must be clear. Estrogen has neuroactive properties that are largely beneficial, that is, it can improve cerebral blood flow, promote axonal sprouting and helps to prevent protein precipitation in the brain pathognomonic of Alzheimer's Disease. However, estrogen and progesterone also have effects on increasing brain excitability which have been demonstrated in animal models of epilepsy, In these settings, estrogen, and to a lesser extent, progesterone, have been proconvulsant. Therefore, an adverse effect of hormone replacement on patients with epilepsy may be postulated. The question posed in this study is, does hormone replacement therapy adversely affect seizures or is it safe for menopausal women with epilepsy? To answer this question, women with epilepsy who are menopausal for at least one year (1 year

36


without menses) and are medically cleared to take hormone replacement therapy will be enrolled. They will be followed for a three month period while taking their usual antiepileptic medications without dosage change. During this prospective baseline period, seizure frequency will be documented. After three months, subjects will be randomized to take either placebo or one of two doses of standard hormone replacement therapy. The hormone replacement therapy used will be Prempro at doses of 1) 0.625 mg conjugated equine estrogens with 2.5 mg medroxyprogesterone and 2) 1.25 mg conjugated equine estrogens with 5 mg medroxyprogesterone. The investigators and the subjects will be blinded as to the study medication given. The subjects will then be followed for a three month prospective treatment phase and again seizure frequency will be documented. Subjects will be monitored for safety concerns regarding hormone replacement therapy and seizure frequency. The outcome of this study will be determined by comparing seizure frequency in the baseline phase with the treated phase between placebo and hormone treated groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT THERAPY AND BREAST CANCER Principal Investigator & Institution: Carney, Patricia A.; Associate Professor; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: The long-term objective of this study is to evaluate the relationships between hormone replacement therapy (HRT) and breast cancer detection, breast cancer risk, breast tumor prognostic characteristics and health-related quality of life. Although the results of numerous case-control and follow-up studies suggest that hormone replacement therapy modestly increases breast cancer risk, most studies have been unable to adjust adequately for frequency of mammographic screening. This is an important limitation because more frequent use of mammography screening among women who maintain hormone replacement prescriptions through regular physician visits may lead to increased detection of breast cancer relative to women who do not use hormone replacement therapy. Our study design, which involves an existing cohort identified through the New Hampshire Mammography Network (NHMN) - a statewide, population-based mammography registry comprising more than 150,000 women - overcomes this limitation. Using a baseline survey, administered at the time of mammography, we have already obtained breast cancer risk factor information, including current HRT use, from all women in the NHMN registry. Through NHMN we have already identified 74,200 women who are pre- or post-menopausal including approximately 26,700 current HRT users. We will follow these women for four years prospectively to ascertain new cases of breast cancer. All NHMN enrollees have already provided permission to link medical, radiologic and pathology data, and consented to further contact for research purposes. We will implement a supplemental survey in Years 1 and 4 to obtain a detailed history of HRT use, additional risk factor information and health-related quality of life. All other data will be obtained from the well established NHMN. Our primary specific aims are to evaluate the impact of HRT on 1) mammography performance (i.e., sensitivity and specificity of screening mammography, proportion of uninterpretable mammograms and consequent use of other imaging procedures); 2) breast cancer incidence (especially combination therapies); 3) breast cancer tumor prognostic characteristics (e.g., TNM stage, tumor grade, axillary lymph node status and estrogen receptor status). As more women consider use of HRT to prevent osteoporosis and other diseases, understanding its

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impact on quality of life is imperative. Therefore, a secondary aim is to assess the impact of HRT on health- related quality of life. Results of the proposed study will benefit radiologists who interpret mammograms, and women and their health care providers, who must balance the complex issues of disease risk and health-related quality of life when deciding whether or not to use hormone replacement therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT THERAPY AND ISCHEMIC STROKE SEVERITY Principal Investigator & Institution: Bushnell, Cheryl D.; Associate in Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Experimental studies in laboratory animals have shown that estrogen reduces stroke severity, but the impact of hormone replacement therapy (HRT) on ischemic stroke severity in humans is not known. There are 2 broad, longterm objectives of this project. The first objective is to determine whether there are differences in stroke severity and outcome between women who are HRT users and women who are nonHRT users. The second objective is to determine whether any difference in these 2 groups is related to enhanced fibrinolysis. The Specific Aims of this proposal are 1) to compare the initial stroke severity in women who are users and nonusers of HRT, 2) to measure any differences in markers of the coagulation and fibrinolytic systems in the acute stroke period, and 3) to assess stroke outcomes in women based on poststroke use or nonuse of HRTs. Subjects for this prospective, observational study will be women admitted with acute ischemic stroke to an academic medical center. In the acute stroke period, initial stroke severity will be assessed using the NIHSS and markers of coagulation (prothrombin fragment F1,2 and thrombinantithrombin III complex) and fibrinolysis (plasminogen activator inhibitor type I) will be measured. Relevant historical and demographic data will be collected. At 3 months poststroke, neurologic impairment (NIHSS), functional status (Barthel Index and Modified Rankin), and quality of life (Stroke Impact Scale) will be assessed. The differences in initial stroke severity will be analyzed accounting for co-variates, and the 3month outcomes will be adjusted for initial stroke severity. This work will provide critical information for physicians prescribing HRT for women at risk for stroke and address whether it is safe to continue these medications in the sub-acute period after stroke. As a K23 proposal, this project will not only provide important clinical information, but is a natural extension of the candidate's previous experience with coagulopathies and stroke, now combined with the commitment to study the impact of stroke in women. This proposal will also provide critical transitional support in a mentored environment leading to the candidate's complete independence as a clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT THERAPY AND LARGE BOWEL CANCER RISK Principal Investigator & Institution: Newcomb, Polly A.; Member and Acting Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 19-AUG-1998; Project End 31-MAY-2004

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Summary: The benefits and risks of estrogen replacement therapy continue to confuse women and their physicians. Recent evidence suggests that estrogen replacement may be associated with reductions in large bowel cancer, a common disease among postmenopausal women. Further study of this potentially important association would provide more precise estimates of the magnitude of effect, identify salient patterns of use, and, importantly, supply insights into the biology of this tumor in women. A population-base case-control study is proposed to evaluate the association between postmenopausal hormones and the occurrence of colorectal cancer. This study will specifically assess use of estrogens with and without progestin, the duration and currency of hormone use, and inter-relationships with body mass. Additional aims of this study are to elucidate the mechanisms of this inverse association, specifically the relationship of HRT to hormone receptors and proliferation in the bowel, and to examine the modifying role of more common cancer susceptibility genes influencing the metabolism of estrogens. Over a three year period, interviews will be conducted with 1,100 women with newly diagnosed cancer of the colon or rectum selected from the population. In addition to the structured telephone interview, fixed diagnostic tissue will be obtained from 540 case in order to evaluate estrogen-receptor status and proliferation markers. Blood samples on a sample of 600 (most with diagnostic tissue) cases and 600 controls will be obtained for genetic studies of polymorphisms relevant to estrogen metabolism and function, specifically CYP17 and the estrogen receptor gene. The proposed study and its extensions should provide clear evidence for the degree to which HRT is protective against colorectal cancer and permit the determination of some of the relevant pathways for that protection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT THERAPY WITH PROGESTERONE CREAM Principal Investigator & Institution: Hermsmeyer, Kent R.; Dimera, Llc. 2525 Nw Lovejoy St, Ste 401 Portland, or 97210 Timing: Fiscal Year 2000; Project Start 13-AUG-1998; Project End 31-AUG-2004 Summary: The objective of this project is to further develop a new progesterone formulation that is effective for hormone replacement therapy-protecting the coronary arteries against hyperreactivity. Such hyperreactivity results from the deficiency of progesterone after the cessation of ovarian function after menopause during the normal aging process. The anticipated new product will be further studied in monkeys in the catheterization laboratory and in human stress test electrocardiogram and echo cardiology protocols. These studies will determine the effectiveness of progesterone in extending treadmill stress test duration, echocardiographic cardiac wall motion, and lipid biochemical measures of coronary function. We will also explore the possible relationship of changes in blood lipids and platelet function. The new formulation is designed to be accepted sufficiently well by postmenopausal women to encourage compliance among those who initiate hormone replacement therapy-for a duration of decades in many cases. Protection of the cardiovascular system by progesterone can be expected to provide for a significant decrease in the incidence of cardiovascular disease during aging, and improved quality of life in post-menopausal women. The skin cream formulation is well accepted by women, has optimal pharmacokinetics for a once a day treatment, and is hypothesized to reduce cardiovascular risks, including coronary artery disease. Even though the risk of death due to cardiovascular causes is nearly 50% for post-menopausal women, and is far greater than any other risk, the presently available forms of hormone replacement therapy are used by only a fraction of those who would

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benefit. This leading risk of death and' available measures to minimize that risk are neither well understood nor readily accepted by post-menopausal women. This formulation has the potential to significantly improve that situation and enhance quality of life in post-menopausal women. PROPOSED COMMERCIAL APPLICATIONS: The percutaneous formulation of progesterone will produce a blood level to minimize the risk of cardiovascular disease, and thus may find widespread application in hormone replacement therapy. The number of people who would be potential consumers for the product consists of all postmenopausal women, a rapidly growing number which already exceeds 20 million. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HRT AND EXERCISE EFFECTS ON CENTRAL ARTERIAL COMPLIANCE Principal Investigator & Institution: Moreau, Kerrie L.; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Candidate. The candidate, Kerrie L. Moreau, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Moreau's past and current research focus has been on physical activity, aging, and cardiovascular health, particularly in women. Her immediate goal is to acquire new research and professional skills to help her achieve her long-term goal of developing a successful independent extramurally-funded research program in aging. The proposed KO1 development plan should provide Dr. Moreau with the necessary training to achieve her goal. Career Development Plan. Dr. Moreau's research career development training activities consist of: 1) acquiring new research skills associated with and complimentary to (e.g., micro array gone expression analysis) the proposed research plan; and 2) structured activities including formal course work; attendance and presentation at journal clubs, seminar series, and scientific meetings; and regular interactions with her mentoring team. Environment. The environment for Dr. Moreau's training should be outstanding. The Sponsor and Co-sponsor, Drs. Douglas Seals and Wendy Kohrt, are well- established extramurally-funded scientists with strong records of successful mentoring in biomedical aging research. They are complimented by several consulting mentors who will provide guidance in specific areas of the training plan. Other faculty in aging research enhance the environment. Research. The general aim will be to determine the relative efficacy of 3 commonly used Hormone Replacement Therapy (HRT) regimens, regular aerobic exercise, and the combination of HRT and exercise for improving central (carotid) arterial compliance, the associated functional benefits, and the underlying mechanisms in healthy sedentary estrogen-deficient postmenopausal women. The general hypothesis is that HRT and exercise will, independently and additively, improve arterial compliance which will, in turn, result in functional benefits (e.g., improvements in cardiovagal baroreflex sensitivity and left-ventricular function/structure), and that these favorable adaptations will be mediated in part by a decrease in sympathetic tone (HRT only) and/or a reduced oxidative stress-associated improvement in vascular endothelium- dependent vasodilatory tone. Moreover, the amount of improvement with hormone supplementation and the additive effect of exercise will differ among HRT regimens. A 2-phase placebo controlled intervention trial employing state-of- the-art measurements of autonomic (e.g. micro neurography) and cardiovascular (e.g., high-resolution ultrasonography) function will be conducted. The expected results should provide new physiological and clinical information concerning the use of various HRT regimens and exercise for the primary prevention of

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reduced central arterial compliance with age and estrogen deficiency, the corresponding autonomic and cardiovascular functional benefits, as well as insight into the underlying mechanisms involved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HRT USE AND RISK OF LOBULAR AND DUCTAL BREAST CANCER Principal Investigator & Institution: Daling, Janet R.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 14-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): Incidence rates of invasive lobular breast carcinomas (ILBC) have increased steadily in the United States since 1977, whereas the trend of increasing incidence of ductal breast cancer has plateaued since 1987. This rise in lobular tumors has occurred specifically among women over age 50. The use of combined estrogen-progestin hormone replacement therapy (CHRT) has also risen steadily over this time period, and recent analyses from two case-control investigations suggest that postmenopausal women who use CHRT may have an increased risk of ILBC, whereas there is no relationship of CHRT to ductal cancer. Few epidemiologic studies have assessed how known or suspected risk factors for breast cancer differ across different histologic types, but such investigations are important because there are likely to be multiple pathways leading to the development and progression of breast cancer of different histologic types. The primary objectives of this proposed study are to confirm recent preliminary findings that CHRT is associated with lobular breast cancer in a large population-based study, to assess this relationship in greater detail, and to explore mechanisms for this association. We propose to conduct a case-control study of 900 women aged 55-79 who have been diagnosed with breast cancer (450 lobular, 450 ductal) and 450 population-based controls who reside in the three county Seattle-Puget Sound metropolitan area of western Washington. The specific questions to be addressed are: (1) Is the use of CHRT associated with an increase in the incidence of invasive lobular breast cancer in women aged 55-79. (2) Is the use of CHRT associated with an increase in the incidence of invasive ductal breast cancer in women aged 55-79? (3) Do the duration, patterns and/or recency of CHRT use influence he size of the association? (4) Is the use of CHRT associated with alteration in the histologic characteristics, tumor cell proliferation, or expression of steroid hormone receptors, oncogenes, and cell cycle and cell death regulator proteins of lobular and ductal breast cancers? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLUENCE ANTINOCICEPTION

OF

GONADAL

HORMONES

ON

OPIOID

Principal Investigator & Institution: Terner, Jolan M.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Previous studies indicate that male rats are more sensitive to the antinociceptive effects of opioids than their female counterparts and that males display higher nociceptive thresholds. Although the gonadal hormones appear to play a critical role in mediating these sex differences, the exact nature of this role remains elusive. The present proposal will systematically evaluate the contribution of gonadal hormones to sex differences in nociception and opioid antinociception using three well-established techniques (i.e., monitoring of the estrous cycle, gonadectomy,

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hormone replacement therapy) and a number of innovative methodological controls. A unique component of this proposal is that it will combine the use of low-efficacy opioids known to produce profound sex differences in opioid antinociception, with the use of divergent strains of rats that differ in the magnitude of their initial sex difference in nociception and opioid antinociception. Experiment I will examine the influence of estrous cycle phase on levels of nociception and opioid antinociception. Although in each phase of the cycle gonadal hormones levels change dramatically, even when hormones are at the lowest levels they may have a profound influence on both nociception and opioid antinociception. Thus, Experiment II will examine the influence of gonadectomy in male and female rats on opioid antinociception in strains that differ in their magnitude of sex differences in opioid antinociception initially observed. Finally, Experiment III will examine the specific gonadal hormones (estrogen, progesterone, and testosterone) involved in mediating nociception and opioid antinociception in male and female rats using hormone replacement therapy. By contrasting the effects of gonadal hormones using three different procedures, controlling for type of nociceptive assay, rat strain and type of opioid, this series of investigations should provide important insight into the role of gonadal hormones in mediating nociception and opioid antinociception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRARENAL REGULATION OF SODIUM EXCRETION Principal Investigator & Institution: Burnett, John C.; Professor of Medicine & Physiology Direc; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 30-JUN-2005 Summary: (provided by applicant): The objective of this renewal application is to elucidate the functional importance of the Natriuretic Peptide System (NPS) in the integrative control of cardiorenal homeostasis with a specific focus upon the pathophysiology and therapeutics of congestive heart failure (CHF) addressing the following working hypothesis. The NPS consisting of the cardiac hormones ANP and BNP and the endothelial cell-derived peptide CNP is activated by ventricular dysfunction representing a protective neurohumoral response that delays progressive cardiac remodeling via renal, vascular and neurohumoral mechanisms which unload the heart. This beneficial neurohumoral mechanism is progressively compromised by the development of a relative NPS deficiency and NPS resistance. Importantly, natriuretic peptide hormone replacement therapy and co-inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme are novel strategies which delay the progression of CHF. Recognizing the increase of dietary sodium intake in the US, the hypothesis that dietary sodium excess contributes to progressive ventricular remodeling via up-regulation of NEP despite the suppression of the renin-angiotensinaldosterone system (RAAS) will also be investigated. We propose integrative physiological studies in a mouse model in which ANP is genetically absent and in a canine model of progressive left ventricular dysfunction (PLVD) with and without experimentally induced ANP deficiency. Therapeutic strategies will include the chronic administration of native natriuretic peptides, novel designer peptides and a possible fourth new member of the NPS-DNP. We will define the potential negative impact of dietary sodium excess upon cardiac remodeling and CHF and establish the role of upregulation of NEP in response to high sodium diet. We will also employ the use of biomarkers BNP and Cardiotropin-l (CT-1) to detect CHF and cardiac remodeling, The Specific Aims are: Aim 1: Establish that the genetic absence of AN? in the mouse is characterized by progressive cardiac remodeling and overt CHF which may be

42


prevented by ANP hormone replacement therapy. Aim 2: Establish in a canine model of PLVD that the presence of an ANP deficiency is characterized by the accelerated development of cardiac remodeling and overt CHF which can be prevented by ANP hormone replacement therapy. Aim 3: Establish that novel therapies that go beyond AN? hormone replacement therapy and are based upon the properties of the NPS delay the progression and severity of progressive cardiac remodeling and overt CHF. Aim 4: Establish that dietary sodium excess accelerates the development of cardiac remodeling and overt CHF in part via up-regulation of NEP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG TERM OUTCOMES FOR WOMEN WITH BREAST CA IN SITU Principal Investigator & Institution: Claus, Elizabeth B.; Associate Professor; Epidemiology and Public Health; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): This project proposes to study the long-term health and lifestyle outcomes for study participants of a population-based case/control study of female breast carcinoma in-situ (BCIS). The study population includes all cases of female BCIS diagnosed among residents of the state of Connecticut from September 15, 1994 to March 14, 1998 as well as a series of random-digit-dial controls also selected from the state of Connecticut. Cases will be between the ages of 20 and 84 years at time of diagnosis while controls are frequency matched to the cases by five-year intervals. Current response rates indicate that the final sample will include approximately 1200 cases and 1200 controls. Baseline telephone interviews have already been conducted with the study subjects and include information on family history of cancer, pregnancy and menstrual history, hormone replacement therapy, oral contraceptive use, as well as socio-demographic variables. In addition, paraffinembedded tumor tissue is being collected for each case to test for the presence of estrogen (ER), progesterone (PR), p53, and HER-2/neu using immunohistochemistry. The current application proposes to recontact study participants at five years from time of initial diagnosis/initial contact. Study subjects will again be asked to participate in a telephone interview to collect updated information on selected topic areas covered in the initial questionnaire such as medical history (breast recurrences, second cancers), family history, pregnancy and menstrual history but also to collect new information on selected measures of well-being and functioning including depression, career, sexual relations, and insurance. In addition, we will ask women to provide us with buccal specimens for BRCA1/BRCA2 testing. The goals of the study are as follows: 1) To provide annual and five-year cumulative estimates of ipsilateral and contralateral breast cancer risk, regional or distant metastatic disease risk, second cancer risk as well as death for women diagnosed with BCIS. 2) To assess the psychosocial impact of BCIS by examining differences between cases and controls on selected measures of well-being and functioning at five years after original recruitment. 3) To measure the association between clinical variables such as hormone receptor positivity and comedo necrosis on outcome for case subjects. 4) To assess the association between epidemiologic risk factors such as age and a family history of breast cancer with outcome, 5) To provide population-based estimates of BRCA1 and BRCA2 in BCIS. 6) To validate/evaluate current histopathologic classification schemes for BCIS with respect to clinical outcome. This project represents one of the first large attempts to assess the survivorship experience of women with BCIS. The data are unique in that epidemiologic, biologic and

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clinical variables will have been collected allowing us to study the relationship of these variables with long term outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONGITUDINAL CHANGES IN HIP GEOMETRY AND SKELETAL MUSCLE Principal Investigator & Institution: Chen, Zhao; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 30-JUN-2008 Summary: (provided by applicant) This study will be conducted among a large multiethnic cohort (N = 11,432) from the nationwide Women's Health Initiative (WHI), which includes an observational study and three clinic trials. The age range of this cohort is between 50-79 years at the baseline, and it has multiple minority groups: 1583 black, 739 Hispanic and 149 Native American women. The maximal follow-up time of this cohort will be 9 years by 2005. Dual-energy x-ray absorptiometry (DXA) is used to measure bone mineral density (BMD) and body composition. The randomized clinical trials and longitudinal nature of the WHI study provide a unique opportunity to investigate: 1) treatment effects of hormone replacement therapy (HRT) and calcium and vitamin D supplementation on hip structural geometry; 2) longitudinal changes in skeletal muscle mass as a factor in hip fragility; and 3) ethnic differences of mean and rates of changes in hip geometry and muscle mass. Special computer software will be used for analyzing hip scans by dual-energy x-ray absorptiometry (DXA). Crosssectional area, subperiosteal width, estimated endocortical diameter, estimated mean cortical thickness, buckling ratio and section modulus at the femoral neck, at the intertrochanteric and the femoral shaft regions will be assessed. MRI scans will be used as references to calibrate total, appendicular and leg skeletal muscle measurements from DXA subregion analyses. Prevalence rates of sarcopenia (low muscle mass) among each age and ethnic group will be studied. Random Effects Models will be used to analyze the longitudinal data. This proposed study is not funded by the WHI program. Recourses that the WHI will provide include DXA scans, fall and fracture data, and information on covariates. Since the majority of data collection work has been or will be done by the WHI, we will be able to cost effectively test multiple important scientific hypotheses in this study. The novel approaches in this ancillary study will enhance scientific contributions of the WHI program. The significance of the proposed study is that it may demonstrate the utility of bone structural analysis in addition to bone mass measurements for understanding ethnic differences in fracture risk and/or for assessing the effect of pharmacologic therapy (i.e. HRT) on bone health. Furthermore, if the muscle variables are found to be a strong determinant of bone structure in the proximal femur and the risk of fall, then it may be important to develop interventions to increase muscle mass in this region to prevent hip fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LONG-TERM COMPLICATIONS OF CHILDREN/ADOLESCENTS & CANCER Principal Investigator & Institution: Green, Daniel M.; Associate Chief; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): We propose to hold a two-day conference on June 28-29, 2002 at Queen's Landing Inn (Niagara-on-the-Lake, Ontario, Canada). The

44


program will be of interest to pediatric hematologists/oncologists, pediatric nurse practitioners, pediatric psychologists, pediatric oncology social workers, medical oncologists, fellows, residents, interns, clinical research associates and other primary care providers. The topic of bone complications following treatment of children and adolescents for cancer will be addressed. The goals of the 7th International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer will be to: 1) Review the biology of the basic multicellular unit; 2) review the role of the kidney in the regulation of calcium metabolism; 3) review the effect of cis-platinum on renal function and calcium metabolism; 4) review the late effects of ifosfamide on the kidney; 5) review the issues involved in the measurement of bone density; 6) review the effects of radiation therapy effects on bone density; 7) review the effects of glucocorticoid hormones on bone density; 8) review the roles of androgen and estrogen in skeletal physiology; 9) review the issues involved in the management of osteoporosis due to ovarian failure; 10) review the role of growth hormone in the regulation of bone density; and 11) review the issues involved in the duration of treatment with growth hormone replacement therapy. The conference will include presentations by nationally and internationally recognized experts in these areas. The conference will facilitate subsequent discussions among the investigators of the Childhood Cancer Survivor Study, most of whom attend this conference, regarding future research on bone complications among participants in the Childhood Cancer Survivor Study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF HORMONE THERAPY IN POSTMENOPAUSAL WOMEN Principal Investigator & Institution: Newby, L K.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The use of unopposed estrogen of combined estrogen/progestin therapy for primary and secondary prevention of coronary disease events in postmenopausal women is gaining favor in the United States. Support for this practice is based largely on epidemiological association of a reduction in the risk of death and non-fatal myocardial infarction in populations of women mostly without prior coronary artery disease who took estrogen for a variety of reasons. The effects of adding a progestin to estrogen are less well studied. Because the potential public health impact from treatment of postmenopausal women with hormone replacement therapy for prevention of coronary artery disease events is enormous, it is imperative to establish a fund of knowledge that supports and aids in the interpretation of clinical trials data to help establish the group or groups for whom treatment should be recommended and when it should be initiated. To accomplish these goals we propose: 1. Using non-invasive measurement of vascular reactivity, to quantify the effect on vascular endothelial function of the addition of progesterone to estrogen therapy in post-menopausal women with and without coronary artery disease. 2. To study the effect of various combinations of postmenopausal hormone therapy on the coagulation system. 3. To use accumulated clinical trials databases to study clinical factors that may influence the efficacy of hormone replacement therapy for secondary prevention of coronary artery disease in postmenopausal women. The propose work will provide additional understanding of the mechanism of estrogen action on endothelial function (which is postulated to be the major mechanism of the beneficial effects of estrogen) and the effects of adding progestins to estrogen replacement regimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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45

Project Title: MELATONIN FOR SLEEP DISTURBANCES DURING MENOPAUSE Principal Investigator & Institution: Suhner, Andrea G.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 16-MAR-2003 Summary: Up to half of all women going through menopause report significant sleep disturbance. A number of factors contribute to these sleep problems, with hormonal imbalance and hot flashes being the most important. Estrogen replacement therapy can alleviate these symptoms, yet side effects and contraindications make the use of this hormone replacement therapy (HRT) problematic in many women. As such, alternatives to traditional HRT are needed. Previous work in our lab has indicated that not only low levels of sex steroids but also the marked increase of gonadotropins observed during the menopause transition may play an important role in disturbed sleep experienced by peri- and postmenopausal women. In particular, our studies have shown that elevated levels of luteinizing hormone (LH) or a high ratio of LH-toestradiol were associated with low sleep- efficiency in postmenopausal women. Hormonal imbalance also induces changes in the thermoregulatory system. The result is hot flashes and sweats, which can adversely affect night-time sleep quality The proposed study will test the hypothesis that exogenous melatonin decreases LH levels and in so doing, increases sleep quality. Furthermore, we hypothesize that melatonin will reduce severity and number of hot flashes by virtue of its temperature-lowering effect. As a consequence, the number of awakenings due to nocturnal hot flashes and night sweats will be reduced, leading to improved sleep quality. To test these hypotheses, twelve symptomatic peri- or postmenopausal women between the ages of 45-55 will ingest a daily dose of 3 mg melatonin or placebo every evening at bedtime over a period of 14 days. Each subject will undergo both conditions. At the end of each treatment session, subjects will spend two consecutive nights in the sleep laboratory. Polysomnographic sleep variables and core body temperature will be recorded continuously on both nights. Hot flashes will be objectively identified by measuring distal skin temperature and proximal skin resistance. Over-night urine samples will be collected to assess LH levels. Sleep parameters, temperature data, number of hot flashes and LH levels will be compared across active and control condition. The current project is an important first step to identify and assess a promising alternative for sleep disturbances in menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENOPAUSE AND MIDLIFE AGING EFFECTS ON SLEEP DISORDERS Principal Investigator & Institution: Young, Terry B.; Professor of Prventative Medicine; Population Health Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-JAN-1997; Project End 31-DEC-2006 Summary: (provided by applicant): The long-range goals of this ongoing longitudinal study of midlife aging in women are to accurately quantify the associations of menopause with the development and progression of sleep apnea and diminished sleep quality and to identify factors that influence the associations. Understanding the role of menopause in the development of sleep apnea and diminished sleep quality has important clinical and public health significance. Sleep apnea and diminished sleep quality are associated with significant cardiovascular morbidity, depression, and decrements in daytime performance. Because menopause will become a persistent state

46


in nearly every woman during her lifetime, even a small effect on sleep apnea and insomnia, the major sleep disorders, would translate into significant morbidity. Furthermore, if associations are causal, understanding whether hormone replacement therapy or other factors significantly modify a menopause-sleep disorder link may lead to interventions that could reduce the occurrence and severity of sleep disorders in midand later life. The proposed study is designed to: 1) Test the hypothesis that changes over the continuum of pre to post menopause increase the incidence and progression of sleep disordered breathing, adjusted for baseline age, body composition, and other potential confounders, 2) investigate the effects of change in body composition during midlife on associations of menopause and sleep apnea, 3) quantify the risk of insomnia, hypersomnia and diminished sleep quality attributable to early, middle and late perimenopause and post menopause, 4) investigate protective effects of hormone replacement therapy on sleep problems, and 5) investigate genetic vulnerability to diminished sleep quality during menopause. To accomplish these aims, we propose additional research on our unique longitudinal cohort of midlife women, with 7-15 years of previously collected polysomnographic and other data with a) new data collected from overnight in-laboratory protocols with polysomnography conducted at 4-year intervals on 621 women enrolled in the Wisconsin Sleep Cohort Study, b) new data collected semi-annually by in-home polysomnography and other procedures and monthly diaries on menstrual characteristics and sleep problems on a subset of 280 women over their pre to peri to post menopausal years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MISSING DATA, MEASUREMENT ERROR AND APPLICATIONS Principal Investigator & Institution: Wang, Ching-Yun; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 15-DEC-1997; Project End 30-NOV-2002 Summary: (Adapted from Investigator's Abstract) Missing or mismeasured regression variables are frequently encountered in the analysis of cancer research data. This problem is a major issue in dietary research, for example. The broad goal of this research is to develop statistical methods for data analysis in the presence of missing or mismeasured regression variables, and to apply these methods to epidemiologic and clinical studies. Specific areas of research include the following: 1) development of a nonparametric regression calibration method for Cox regression when validation data are available; 2) development of methods for Cox regression with reliability data; 3) development of methods for logistic regression analysis using conditional exposure mean for missing or mismeasured exposures; and 4) development of methods for characterizing associations between multiple variables. Asymptotic theory will be developed and simulation studies will be conducted. The methods will be applied to data from the Women's Health Initiative, a large disease prevention trial and observational study involving 164,500 women with the objective of evaluating the benefits and risks of dietary modification, hormone replacement therapy and supplementation with calcium and vitamin D on the overall health of postmenopausal women. The investigator states that the proposed methods will also accommodate twostage designs which are becoming popular in epidemiologic research and particular in genetic epidemiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODIFYING OXIDATIVE DAMAGE IN WAVE Principal Investigator & Institution: Steffes, Michael W.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: Supplemental vitamin E has been associated with a reduced risk of recurrent myocardial infarctions, with efficacy related to dosage and the duration of treatment. Its effects may be enhanced by vitamin C, an antioxidant that can regenerate vitamin E activity. Theoretically vitamin E and C (VitE/C) accumulate in the vascular wall with a concurrent reduction in oxidative damage, a primary feature of atherosclerotic lesions. Estrogen/hormone replacement therapy (HRT) also may reduce oxidative damage, and it may enhance the effect of vitamin E and C. These hypotheses are supported by studies defining oxidation-dependent accumulation of lipids in developing atherosclerosis; the detection of oxidative damage products, such as oxidized-LDL particles, in human atherosclerotic lesions; and clinical studies associating antioxidant or estrogen supplementation with reductions in oxidative damage cardiovascular disease. Nevertheless, no human studies have evaluated the effect of long-term VitE/C treatment, which has been reported as being the most effective prevention factor by epidemiologic studies, on specific. biochemical markers of oxidative damage and concurrently their association with recurrent cardiovascular disease. In addition, no studies have characterized the effect of long-term HRT on markers of oxidative damage or HRT's potential synergistic effect with VitE/C therapy. We propose assaying specific biochemical measures of oxidative damage (all markers at closeout and nitrotyrosine and chlorotyrosine also at baseline) in the Women's Angiographic Vitamin and Estrogen (WAVE) Trial, which randomized 420 38-86 year old women with a prior cardiovascular disease event to placebo, VitE/C, HRT or the combination of VitE/C and HRT. WAVE will determine the efficacy of these treatments on quantitative angiographic evaluation of minimal coronary artery diameter performed at baseline and at the final visit to be completed during the first 10 months of 2001. We will measure oxidation products from several classes of compounds (lipids by F2-isoprostanes, proteins by nitrotyrosine and chlorotyrosine, and DNA by 8-hydroxy-2'-deoxyguanosine), thereby studying several major pathways that may lead to atherogenesis. In addition, inflammation with Creactive protein, platelet activation with p-selectin, altered lipid metabolism with a lipid profile and other characteristics of the study population will be integrated into the assessment of oxidative damage in WAVE. By measuring these various factors and by assessing oxidative damage in several classes of compounds, we can test the relationships among specific pathways of oxidative damage, supplemental VitE/C and/or HRT and other risk factors upon the progression of established macrovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUTATIONS, THROMBOEMBOLISM

HORMONE

THERAPY,

AND

VENOUS

Principal Investigator & Institution: Psaty, Bruce M.; Professor, Medicine and Epidemiology; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from Investigator's Abstract) Epidemiologic studies have identified Factor V Leiden as the most common cause of heritable thrombophilia a prothrombotic mutation associated with a 5 to 7-fold increase in the risk of venous thromboembolism

48


(VTE). In pre-menopausal women, the use of oral contraceptives is associated with a 4fold increase in VTE risk, and the joint effects of oral contraceptive use and Factor V Leiden carriership increase the VTE risk of by a factor of 35 (95% IC = 8 154). Recently, the results of several observational studies and randomized clinical trials suggest that in post-menopausal women, the use of hormone replacement therapy is associated with a 3-fold increase in VTE risk. Whether post-menopausal women with prothrombotic mutations experience a similar 20-fold increase in risk when they take post-menopausal hormones remains unknown. The primary aim of this ancillary study is to assess the interaction between hormone replacement therapy and the prothrombotic mutations, Factor V Leiden and the recently described prothrombin mutation (20210A) on the incidence of VTE in a population-based case-control study conducted at Group Health Cooperative of Puget Sound (GHC). The investigators state that using a variety of computerized surveillance systems at GHC will enable them to identify both in-patient and out-patient episodes of venous thromboembolism. They anticipate recruiting 300 post-menopausal women with a first episode of objectively confirmed venous thromboembolism, and 1,200 population-based controls will be identified and recruited from the GHC enrollment files. Controls will be frequency matched to the cases on age and calendar-year. Data collection includes a review of ambulatory medical record and a telephone interview. The GHC computerized pharmacy database will be used to assess exposure to hormone replacement therapy. A venous blood specimen will be obtained from consenting subjects, processed into aliquots of white cells, plasma, and red cells, and stored at 70 degrees C prior to laboratory analysis. DNA will be extracted from white cells, and molecular genotyping assays will be conducted to assess carriership of prothrombotic mutations. Data from these various sources will be entered, linked and analyzed to address the specific aims. Under an additive model, the expected joint effects of HRT and carriership of prothrombotic mutations is 7. Compared with the null hypothesis for the additive model of a joint effect of 7, the investigators have 80% power to detect a difference between the alternative hypothesis of 18 and the null hypothesis of 7. If there is an important interaction between hormone replacement therapy and prothrombotic mutations, such a finding would offer important opportunities of VTE risk reduction by pre-treatment screening in the clinical setting for the prothrombotic mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN HORMONE EFFECTS OF MUSCLE INJURY AND RECOVERY Principal Investigator & Institution: Schneider, Barbara A.; None; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2005 Summary: (provided by applicant): In the United States, there are about 57.6 million athletic and physically active women. More women are participating in high-intensity sports activities than ever before. Consequently, women as well as men are at risk for eccentric contraction-induced injury. Eccentric contraction-induced injury occurs when the extrinsic load on a stretched muscle exceeds the amount of force produced by that muscle. However, there are no criteria that enable health care providers to effectively predict which group(s) of women (e.g., premenopausal women and/or women taking oral contraceptives or hormone replacement therapy) have an increased susceptibility to develop eccentric contraction-induced injury. The long-term objective of our research program is to understand how personal factors, such as gender, influence eccentric contraction-induced injury and recovery. Limited study suggests that female gender

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may be one personal factor. The specific aims of the proposal are to determine the independent and interactional effects of estradiol and progesterone on 1) susceptibility to develop eccentric contraction-induced injury and 2) host defense (inflammatory) response to eccentric contraction-induced injury. The hypotheses are 1) estradiol alone increases injury susceptibility; 2) progesterone attenuates the estradiol increased injury susceptibility; and 3) a combination of estradiol and progesterone delays recovery by inhibiting and delaying the host defense response to eccentric contraction-induced injury. The hypotheses will be tested using intact mice (mice that have ovaries) and ovariectomized mice (mice that have had their ovaries surgically removed). The ovariectomized mice will be treated with placebo, estradiol alone, progesterone alone, or a combination of estradiol and progesterone. Slow-twitch and fast-twitch muscles of both intact and ovariectomized mice will undergo eccentric contraction-induced injury. Then functional and structural changes and magnitude of macrophage infiltration will be measured in injured muscles. Findings may have implications for women of varying ovarian hormone status when they engage in high-intensity eccentric contractions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYTOESTROGENS AND PROGRESSION OF ATHEROSCLEROSIS Principal Investigator & Institution: Hodis, Howard N.; Associate Professor; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The fear and discontent with traditional hormone replacement therapy (HRT) coupled with the interest in natural products has resulted in an increased use of soy protein as a postmenopausal therapeutic alternative by both women and their physicians alike. Evidence from epidemiological and non-human primate studies indicate that isoflavone-rich soy protein has antiatherogenic activity, evidence supported by a large body of data that indicate mechanistic and biologic plausibility. No studies to our knowledge have been published or proposed to determine the long-term effects of soy protein on the progression of atherosclerosis in postmenopausal women. We propose to conduct a 2.5-year, randomized, double-blind, placebo-controlled trial of isoflavone-rich soy protein in 300 healthy postmenopausal women without clinical evidence of cardiovascular disease. We hypothesize that relative to placebo, isoflavone-rich soy protein (supplying genistein, daidzein and glycitein) will reduce the progression of subclinical atherosclerosis in healthy postmenopausal women. The primary end point will be the progression of subclinical atherosclerosis measured as the rate of change in common carotid artery intima-media thickness in computer image processed B-mode ultrasonograms, a well-established noninvasive arterial imaging end point for antiatherosclerosis trials, lsoflavone-rich soy protein may provide a safe and effective alternative approach for extending premenopausal cardioprotection afforded by endogenous estrogen into menopause without the increased risk of thromboembolic events and certain cancers associated with traditional HRT. Since many postmenopausal women are using soy products to maintain their health, it is important to understand whether soy protein has an antiatherogenic effect so that women can make a truly informed decision concerning their expectations of this form of postmenopausal therapy. The question as to whether soy protein is effective in reducing the progression of atherosclerosis in postmenopausal women is not only timely, but also of immense medical and financial importance since atherosclerosis remains the number I killer of postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POST ABDOMINAL FAT

MENOPAUSAL

HORMONE

THERAPY

AND

INTRA

Principal Investigator & Institution: Gower, Barbara A.; Associate Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: Background: Hormonal and metabolic changes associated with the menopause may confer increased risk for cardiovascular disease (CVD). Data indicate that the postmenopausal period is associated with increases in total and central ("android") body fat; increases in the atherogenic components of the blood lipid profile; and deterioration of glucose tolerance - all risk factors for CVD. Changes in lipid and glucose metabolism may be secondary to accumulation of central fat, particularly intraabdominal fat (IAF), the compartment associated with dyslipidemia and insulin resistance. Hormone replacement therapy has positive effects on the lipid profile in postmenopausal women, and may affect regional fat deposition. However, the extent to which the beneficial effects of hormone therapy on disease risk factors are mediated by changes in fat distribution is not known. Few studies have examined the effects of hormone replacement therapy on body composition and fat distribution, and non have examined the effect of exogenous hormones on IAF, the adipose compartment most closely associated with disease risk. Objective: To test the hypothesis that hormone replacement therapy (HRT, combined estrogen-progestin) in postmenopausal women decreases risk by limiting IAF deposition. The proposed research will examine the effect of HRT on total, regional, and intra-abdominal fat deposition, and on the relationships between adiposity, the plasma lipid profile, and glucose metabolism. Design: Longitudinal cohort study of 140 early postmenopausal women using or not using HRT. A baseline assessment (within the first year of hormone use) and one 2-year follow-up assessment will be conducted. Total body fat will be assessed with dual-energy X-ray absorptiometry, hydrodensitometry, and deuterium dilution; and regional adiposity (thigh, abdominal, intra-abdominal) will be quantified with computed tomography. Circulating levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides will be determined. Insulin sensitivity and glucose tolerance will be assessed with the tolbutaminde-modified, frequently-sampled, intravenous glucose tolerance test and minimal modeling. Significance: HRT reduces risk and incidence of CVD in postmenopausal women. This study will determine if HRT reduces disease risk by influencing fat distribution and decreasing IAF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG Principal Investigator & Institution: Ouyang, Pamela C.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 15-AUG-1996; Project End 31-JUL-2004 Summary: Coronary atherosclerosis is a major cause of death in women in the USA. Although coronary artery bypass surgery decreases symptomatic and clinical evidence of ischemia, it does not alter the underlying process. Patients may present several years later with recurrent symptoms that may be a result of occlusion of saphenous vein grafts, development of atherosclerotic disease in the vein grafts, or progression of underlying disease. Any intervention that can reduce the rate of progression of coronary atherosclerosis following bypass surgery would provide significant benefit for women following bypass surgery and possibly for other women with atherosclerotic disease.

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Observational studies suggest that postmenopausal estrogen replacement therapy is associated with a reduction in cardiac morbidity. However the benefit for hormone replacement therapy in women with established coronary disease has not been demonstrated. This randomized, double-blind controlled trial tests the hypothesis that postmenopausal hormone replacement therapy in women following coronary bypass surgery will reduce the occurrence of graft occlusion and delay the development of graft atherosclerosis. Women will be randomized to esnadiol with daily medroxyprogesterone or placebo within 4 weeks of bypass surgery. Graft occlusion and development of vein graft atherosclerosis will be measured by comparing quantitative coronary angiographic and intravascular ultrasonographic assessment of disease severity and extent performed at 6 months and 3.5 years after randomization. The primary outcome variables will be the occurrence of graft occlusion at 6 months and the change in severity and extent of atherosclerosis in the saphenous vein grafts over 3 years. The proposal will determine th influence of hormone replacement therapy on the primary outcome variables. The pathophysiologic mechanisms of interest in this proposal are platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors and lipoprotein composition. The proposal will test the hypothesis that these variables predict the occurrence of graft occlusion and rate o development of graft atherosclerosis. The proposal also tests the hypothesis that hormone replacement therapy exerts its beneficial effects by its effects on those risk factors in addition to more traditional risk factors including the lipids and lipoprotein profile. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTMENOPAUSE CHD RISK: PLATELET GENES & HORMONE THERAPY Principal Investigator & Institution: Bray, Paul F.; Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 27-SEP-2003; Project End 31-AUG-2007 Summary: Coronary heart disease (CHD) is the number one killer of women in the United States. Hormone replacement therapy (HRT) with estrogen (E) and progesterone (P) should probably no longer be considered cardioprotective. In fact, data from the HERS and WHI studies indicate E+P may increase myocardial infarction (MI) and stroke despite its beneficial effects on cholesterol levels. Since blood platelets play a central role in the pathophysiology of MI and stroke, these findings raise questions about the effect of HRT on platelet thrombus formation in coronary vessels. Our published and preliminary data show that 1) female platelets are hyperreactive compared to male platelets, 2) sex hormones enhance platelet reactivity, 3) platelets express estrogen receptor (ER) beta and ER alpha, 4) functional platelet polymorphisms are risks for CHD, and 5) there are pharmacogenetic interactions between functional polymorphisms of platelet genes and specific cardiovascular therapies (aspirin, statins, and GPIIb-Illa blockers). Because women are at least as predisposed as men to genetic influences on CHD development, we hypothesize that inherited platelet variants dictate which postmenopausal women are susceptible to the prothrombotic effects of HRT. Our goal in this proposal is to identify genetic predictors of CHD events in women. We will perform a case-control study on the Observational Study of the Women's Health Initiative, analyzing DNA from 1,060 women who have experienced a CHD death or documented nonfatal MI (cases) and from 2,120 controls not having a CHD event. With this large number of CHD cases and controls we will test for associations between functional platelet polymorphisms and CHD events (Aim 1) and interactions between

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these polymorphisms and HRT as a risk for CHD events (Aim 2). We have assembled an excellent group of investigators and have an extremely valuable resource, putting us in a unique position to achieve these goals and our long-term goal of optimizing the prevention and management of CHD in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGESTERONE AND SLEEP IN OLDER WOMEN Principal Investigator & Institution: Moe, Karen E.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-DEC-2004 Summary: Sleep complaints increase significantly with age in women. Many older women experience difficulty falling asleep, more night-time awakenings, and less restful sleep. Sleep studies verify that disturbed sleep patterns are observed even in healthy older women. Sleep disturbances are associated with increased daytime drowsiness, increased accident risk, increased use of health care, and reduced quality of life. Older women receive a disproportionate number of sedative-hypnotic medications, which can exacerbate sleep apnea and have daytime carryover effects such as sedation, falls and subsequent fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be menopause-related changes in sex steroids such as estrogen and progesterone. Research attention has focused on estrogen. However, progesterone may also participate in the control of sleep. Clinical reports indicate that women often feel drowsy after they take oral progesterone - an effect which is undesirable during the day, but may be positive at night. To date there are no published studies of progesterone's effect on the objectivelymeasured sleep and daytime drowsiness of older women. The proposed study will take a systematic, multi-dimensional approach to determining the effect of progesterone on the sleep and drowsiness of older women. Objective techniques (polysomnography, Multiple Sleep Latency Test) will be used to measure sleep and daytime drowsiness following evening or morning administration of 300 mg micronized progesterone, in 40 postmenopausal women who are at least 5 years past menopause and who are not experiencing hot flashes. Attention, memory, subjective sleepiness, and blood levels of progesterone and its metabolite (allopregnanolone) will also be measured. This study is part of a long-term research plan to assess (1) how the very low postmenopausal levels of estrogen and progesterone contribute to sleep difficulties of older women, and (2) how hormone replacement therapy affects the sleep of women. An ongoing placebocontrolled study is investigating the effects of estrogen on the sleep of older women. The proposed study will complement the estrogen study. It will enhance our limited understanding of the relationship between sex steroids and sleep, and the factors that contribute to sleep problems in older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTECTING SLEEP QUALITY IN LATER LIFE Principal Investigator & Institution: Reynolds, Charles F.; Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: Good sleep quality is important to continued adaptability, physical and mental health in late life. After age 75, however, loss of sleep continuity and depth accelerates, presaging diminished adaptability and decrements in health status. Protecting sleep quality in late life therefore may be important to continued healthy

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aging. We propose to test this hypothesis by examining the ability of sleep hygiene education and restriction of time in bed: (1) to slow or reverse age-dependent loss of sleep continuity and depth and thereby (2) to promote stability or improvement in daytime wellness, mental and physical health in the later years of life. In this revision of AgeWise Project 4, we will recruit 99 elders aged 275 without sleep-wake complaints, randomly assign them (33 per cell) to one of three conditions (education in healthy sleep practices ["education"], education in healthy sleep practices plus restriction of time in bed ["education" plus "restriction"] or an attentiononly control condition) and follow them for 30 months, measuring sleep, well being, and physical and mental health at baseline (T1), six months (T2), 18 months (T3), and 30 months (T4). We predict that the combined intervention condition ("education" plus "restriction") will be associated with preservation of better sleep quality and, hence, with better adaptation and health over 2.5 years than education in sleep practices alone or an attention-only control condition. We will employ random regression analyses to model long term trajectories in outcome measures of health, well being, and functional status associated with the three intervention conditions. In these analyses we will covary for the presence/absence of hormone replacement therapy, as well as for knowledge of sleep and expectancy effects. This prediction embodies the basic premise of the AgeWise program project, namely, that continued successful aging is promoted by protecting and enhancing sleep quality in late life. Program-wide research in this project will also test that more stable sleep-wake schedules and modest reductions in time in bed will in general be associated with better sleep, mental health, physical health and well being in the final years of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RALOXIFENE EFFECTS ON COGNITION IN EARLY MENOPAUSE Principal Investigator & Institution: Upchurch, Margaret B.; Professor; Psychology; Transylvania University 300 N Broadway Lexington, Ky 40508 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 30-APR-2004 Summary: Applicant?s Hormone replacement therapy (HRT) in women is commonly used to diminish the physical symptoms of menopause and to reduce the risk of disorders such as osteoporosis, heart disease, and atherosclerosis. HRT may have by its own risks, in particular, an increased chance of developing endometrial or breast cancer. In an effort to reduce these risks, some physicians are prescribing the selective estrogen receptor modulator (SERM) raloxifene (trade name Evista) for the prevention of osteoporosis. Estrogen also has cognition-enhancing capabilities in postmenopausal women and may serve to prevent or delay the onset of Alzheimer?s disease. Because raloxifene can function as either an agonist or antagonist at estrogen receptors, it is not known whether it too may affect cognitive function. The goals of this study are to examine the cognitive function of women in the perimenopausal period and to compare the effects of estrogen replacement and raloxifene treatment on cognitive function. The women in the two replacement groups will be compared with same-aged women who are still menstruating and to same-aged postmenopausal women who are not on HRT. The research will therefore compare the function of age-matched women with cyclic variation in estrogen levels (premenopausal), consistently high estrogen levels (postmenopausal, HRT-estrogen), consistently high SERM levels (postmenopausal, HRT-raloxifene), and consistently low estrogen levels (postmenopausal, no HRT). The tests will assess verbal recall and mental rotation skills, cognitive abilities that are influenced by estrogen levels. Digit span and Trail-Making Test performance, skills for which there is little evidence of an estrogen effect, will also be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REPRODUCTIVE HORMONES AND PRE-CLINICAL CVD IN WOMEN Principal Investigator & Institution: Bairey Merz, C. Noel.; Associate Professor and Medical Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Cardiovascular disease is the leading killer of women, yet prior research has failed to provide any clear understanding of the gender gap wherein women appear to be relatively protected from CVD while premenopausal, compared to men. Recent randomized trials of hormone replacement therapy (HRT), described below, have failed to demonstrate CVD benefit, and call into question the "estrogen protection" hypothesis. Alternative explanations for the gender gap, e.g., androgen exposure, have not been explored. This application, developed in response to the NHLBI's Innovative Research Grant Program Request for Application HL-01-016 and using existing data sets and biological specimens, is designed to support collaborative feasibility research in an innovative and high impact area relevant to CVD in women. The overall aim of this application is to use the existing data and stored blood samples from the NHLBI-sponsored Los Angeles Atherosclerosis Study (LAAS, HL-490-10) to explore new and innovative hypotheses with regard to reproductive hormones and progression of pre-clinical cardiovascular disease (CVD), measured by carotid intima-media thickness (IMT), in the 269 women (45% minority) in the Los Angeles Atherosclerosis Study (LAAS), an ongoing NHLBI-sponsored study of employed utility workers in Southern California without CVD at study entry. Hormonal assays will be performed on stored samples by a NHLBI Reproductive Hormone Core Laboratory, and subsequent analyses will characterize relationships to carotid IMT measured by the LAAS Ultrasound Core Laboratory. The following hypotheses will be test ed: 1) Reproductive hormonal profiles characterized by a relative estrogen deficiency and/or relative androgen excess will be directly correlated with increased baseline carotid IMT and predict greater carotid IMT progression over time in women; 2) Reproductive hormone effects on carotid IMT progression will be observed dominantly in situations of intimal injury, e.g. cigarette smoking, hypercholesterolemia, hypertension or diabetes in women. Innovative aspects of this application include evaluation of reproductive hormones repeatedly and prospectively in women across the spectrum of menopause (pre-, peri- and post-) using innovative methodologies including the sensitive reproductive hormonal assays used in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) core laboratory, and a newer quantitative carotid intimal media thickness (carotid IMT) protocol from the NHLBIsponsored LAAS. The current application represents an opportunity to gain feasibility pilot data in the area of the role of reproductive hormones and CVD in women using novel measures and a collaborative approach in order to plan further investigation, if warranted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REPRODUCTIVE/CONTRACEPTIVE ENDOMETRIOSIS

RISK

FACTORS

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Principal Investigator & Institution: Holt, Victoria L.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-MAY-1997; Project End 30-APR-2006

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Summary: (provided by applicant): Endometriosis affects 5-10% of reproductive-age women with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Medical treatment with 6 months of danazol or a GnRH agonist and surgical treatment are effective in alleviating symptoms in the short term, but the side effects of medical and surgical intervention preclude indefinite continuation or repeated treatment, and symptoms reoccur in 40-50% of women after treatment cessation. Knowledge of risk or protective factors for recurrence is of great importance, therefore, yet the effect of patient characteristics and behaviors on symptom recurrence likelihood has largely been unexamined. The main objectives of this competing continuation application are to determine the 48-84 month symptom recurrence rate in a cohort of 18-49 year old women with a first-time diagnosis of endometriosis, according to disease severity and treatment, and to assess relationships between symptom recurrence and estrogenrelated subject characteristics and behaviors. The study hypothesis is that factors associated with higher estrogen levels, including lack of regular exercise, peripheral body fat distribution, alcohol use, dietary phytoestrogen ingestion, presence of low activity alleles in genes involving estrogen metabolism, and use of hormone replacement therapy, may increase long-term risk of endometriosis symptom recurrence after treatment cessation. The proposed retrospective cohort study will utilize cases (n=337) from the principal investigator's current case-control study of endometriosis risk factors (Reproductive/Contraceptive Risk Factors & Endometriosis, R01 HD33792) conducted within a large health maintenance organization in Washington State. Information available from the cases in that study, including in-person interviews with pre-diagnosis details of medical, reproductive, menstrual, contraceptive, behavioral, and other characteristics; dietary and anthropometric measurements; and values of 4 genetic polymorphisms (GSTM1, COMT, CYP1A1, CYP1A2) will be combined with additional interview information to be collected between 48-84 months after initial diagnosis on treatment details, timing and extent of any recurrence of symptoms, and post-diagnosis estrogen-related characteristics and behaviors. Medical records and pharmacy records will be used as to supplement subject-provided diagnosis, treatment and recurrence information. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH RESOURCES CORE D--METABOLIC FUNCTION AND BODY COMPOSITION Principal Investigator & Institution: Yarasheski, Kevin E.; Associate Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This study involves two protocols: 1) the extent to which frail, old men (n=80) can respond to 9 months of exercise training with the cardiovascular, musculoskeletal, and central nervous system adaptions that have been shown to occur in younger people and 2) if hormone replacement therapy (HRT) can reduce frailty in old women (n=120) with physical frailty, and to determine if 9 months of exercise training brings about greater improvements in old women who have been on HRT for 9 months than in sex hormone deficient women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK FACTORS FOR CVD IN WOMEN Principal Investigator & Institution: Manson, Joann E.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115

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Timing: Fiscal Year 2002; Project Start 01-DEC-1984; Project End 31-AUG-2007 Summary: (provided by applicant): This study will examine promising but as-yetunproven biochemical, genetic, and lifestyle predictors of coronary heart disease (CHD) and stroke in a prospective cohort of 121,700 US women currently aged 55-80 years. Blood samples were collected from 32,826 participants in 1989-1990, and detailed nutritional, behavioral, and lifestyle variables have been collected for more than 25 years. A major aim is to compare the predictive capability of several biochemical and genetic markers of inflammation and endothelial activation for CHD versus stroke in women: C-reactive protein (CRP), E-selectin, intercellular adhesion molecule-1, endothelin-1, and polymorphisms of the CRP and E-selectin genes. Few studies have directly compared risk factors for both CHD and stroke, although this information is essential from public health and screening standpoints. This proposed work will also continue the investigation of lifestyle determinants of cardiovascular disease, including hormone replacement therapy (dose, formulation, and duration of use) and alcohol consumption (dose and beverage type), in the full cohort and interactions of these exposures with the above biomarkers and with novel genetic markers (prothrombin and alcohol dehydrogenase-3 gene polymorphisms). By 2004, an estimated 834 cases of CHD (nonfatal myocardial infarction and fatal CHD) and 453 cases of ischemic stroke will have been confirmed among women in the blood cohort, and 3,442 cases of CHD and 1,378 cases of ischemic stroke among women in the overall cohort. The Nurses' Health Study has a long, established record of important findings on predictors of cardiovascular disease in women. The large size, prospective design, high follow-up rates, detailed and reliable long-term exposure and outcome information, and the availability of blood specimens on a large subgroup, combined with the relatively low cost, make this cohort a valuable and unique resource for studying biochemical and genetic determinants of cardiovascular risk in women. The results of this work may lead to new strategies for identifying women at high risk of cardiovascular disease as well as new approaches for cardiovascular disease prevention and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ESTROGEN IN EXERCISE-INDUCED VEGF EXPRESSION Principal Investigator & Institution: Entin, Pauline L.; Northern Arizona University Department of Biological Sciences Flagstaff, Az 86011 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): A training-induced increase in muscle capillarity appears to contribute to the reduced risk of cardiovascular disease and type two diabetes associated with aerobic fitness. Vascular endothelial growth factor (VEGF), a potent initiator of angiogenesis, is upregulated in cardiac and skeletal muscle by exercise. Estrogen also enhances VEGF expression, but the interactive effect of estrogen and exercise on VEGF in muscles has not been studied. The proposed study tests the theory that estrogen status affects exercise-induced upregulation of VEGF in cardiac and skeletal muscle. Four specific hypotheses will be addressed: 1. The levels of VEGF mRNA and protein are lower in the cardiac and skeletal muscles of estrogen-depleted, sedentary female rats than sedentary females rats with normal estrogen levels; 2. Exercise-induced upregulation of VEGF mRNA and protein are attenuated in the cardiac and skeletal muscles of estrogen-depleted female rats; 3. The levels of VEGF receptor (Fit-1 and FIk-1) proteins are attenuated in the cardiac and skeletal muscles of sedentary and exercised estrogen-depleted female rats; 4. Exogenous estrogen replacement restores exercise-induced VEGF mRNA and protein upregulation to control levels in the cardiac and skeletal muscles of estrogen-depleted female rats. These

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hypotheses will be tested using six groups of 6 mo. female Fischer 344 x Brown Norway rats (n=7 per group): sedentary control; sedentary ovariectomized (OVX), exercise control, exercise OVX, sedentary OVX with estrogen replacement, and exercise OVX with estrogen replacement. Rats in the exercise groups will be run once for 45 min at 20 m/min, 10 degree incline, an intensity previously shown to induce a 4 to 6-fold increase in VEGF mRNA in 6 mo. female Fischer 344 rats. VEGF mRNA levels in the heart and gastrocnemius will be analyzed by real-time PCR. VEGF and VEGF receptor protein levels will be assessed by Western blot. Analyses will be done using two-way ANOVA (exercise status, estrogen status). The results of this study will contribute to the assessment of the risk/benefit ratio for hormone replacement therapy, particularly in the context of those at risk for cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SERUM MARKERS OF BREAST /OVARIAN CANCER RISK Principal Investigator & Institution: Modugno, Francesmary; Assistant Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Both breast and ovarian cancers are costly in terms of morbidity and mortality to women. While both diseases have some well-defined behavioral risk factors, there are few, if any, established biomarkers of risk. Moreover, there are a paucity of markers that have the possibility to be applied in a clinical setting, and there is a lack of prospectively collected data and serum samples available to researchers to explore new risk markers. Such markers, tested in a large, prospective setting, are urgently needed in order to identify women at an increased risk for these diseases, as well as to improve our models of risk assessment and to devise effective prevention strategies. We have formed a multi-institutional consortium linked to an ongoing multi-center trial in order to evaluate prospectively the utility of serum biomarkers as risk factors for breast and ovarian cancers. In particular, we will (1). determine prospectively the effects of serum markers of estrogen metabolism, body mass index (BMI), and hormone replacement therapy (HRT) on postmenopausal breast cancer risk; and (2). determine prospectively the association of insulin related serum biomarkers on postmenopausal ovarian cancer risk. To achieve our objectives, we will undertake two nested case-control studies within the Observational Study (OS) of the Women?s Health Initiative (WHI), a multi-center prospective study of women?s health funded by the NIH. The first study will compare BMI, HRT and estrogen metabolite levels in WHI banked serum between 200 confirmed cases of invasive breast cancer and 200 healthy women frequency matched by age, race and study site. The second study will compare insulin, glucose and insulin-like growth factor levels in WHI banked serum between 200 confirmed cases of epithelial ovarian cancer and 200 healthy women frequency matched by age, race, study site and HRT status. Risk factor, confounding and outcomes data has already been collected and verified by the WHI Clinical Coordinating Center and will be provided to us in a clean study database. All laboratory assays will be performed by experienced, collaborating investigators with whom we have worked in the past. Justification for our studies comes from preliminary data we have generated. Approval to undertake this collaboration has already been obtained from the WHI. By the end of this project, we will have prospectively evaluated some new and promising serum markers of risk for breast and ovarian cancer. We also expect to identify additional related research questions, which we anticipate studying further in a multi-center, collaborative fashion within the various arms of the WHI.

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Project Title: SLEEP DISTURBANCE IN MENOPAUSE Principal Investigator & Institution: Freedman, Robert F.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: At present, over 35% of the women in the United States have reached the median age of menopause, 51 years. Hot flashes (HFs) are the most common symptom of the climacteric and occur in the vast majority of postmenopausal women. Sleep disturbance has also been reported to be highly prevalent in this population. Yet, the causal links, if any, between these 2 phenomena are I not known. In the studies proposed here, we will attempt to discern the relationships among Hfs and objective and subjective sleep disturbance. In Study 1, we will record sleep and HF parameters in postmenopausal women with HFs, those without HFs, and age-matched premenopausal women without HFs. We will perform quantitative EEG analyses, use an objective test of daytime sleepiness (MSLT) and assess subjective sleep quality with established instruments. HF frequency increases with ambient temperature. If HFs produce arousals and thereby disrupt sleep, then reducing ambient temperature should improve sleep and increasing temperature should worsen it (Study 2). Increased arousal frequency has been found in postmenopausal women with HFs. If this accounts for reports of poor sleep, then experimental sleep disruption in asymptomatic women should produce reports of poor sleep, as well. In Study 3, we will use yoked groups of symptomatic and asymptomatic women and disrupt sleep of the latter group based on recordings from the former group. We will do this using a stimulus specific to HFs (ambient heating). Despite the common use of hormone replacement therapy, its effects on sleep have not been established. In Study 4, we will systematically manipulate ambient temperature during sleep in symptomatic women before and during estrogen replacement and in a placebo-control group. In Study 5, we will determine the effects of elevated sympathetic activation on HFs and sleep using a stimulus that does not, by itself, disrupt sleep (orthostasis). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP DURING THE PERI-MENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Gold, Ellen B.; Director; Epidemiology and Prev Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 30-SEP-2005 Summary: (provided by applicant) This interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African-American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in midlife women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep-menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in mid-life women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness

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and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women s Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study, participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC Davis PIs will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP DURING THE PERIMENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Hall, Martica; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 30-SEP-2006 Summary: This Interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African- American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in midlife women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep- menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in midlife women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women's Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study, participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants' homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques

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will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC Davis PIS will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOY AND LIPOPROTEINS IN POSTMENOPASUAL WOMEN Principal Investigator & Institution: Allen, Jerilyn K.; Associate Professor; None; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Cardiovascular disease (CVD) remains the leading cause of mortality and disability in postmenopausal women. Menopause alters serum lipids and lipoproteins to produce a more atherogenic lipid profile that may contribute significantly to the increased risk for the development of CVD over the lifetime of women. Clinical trials have demonstrated a beneficial effect of soy protein containing isoflavones (soy) on plasma lipids and lipoproteins; however, these studies included small numbers of postmenopausal women and virtually none included sufficient African-American women. In addition, no published data exist on the impact of soy on atherogenic lipoprotein subclasses in postmenopausal women. Therefore, the primary aim of this study is to determine the effects of soy on lipids, lipoproteins and lipoprotein subclass in a sample of African-American and white postmenopausal women with lowdensity lipoprotein (LDL) cholesterol elevations that may increase their lifetime risk for CVD but would not qualify for definite pharmacotherapy under current guidelines. The secondary aims are to assess the impact of soy on menopausal quality of life, including menopausal symptoms, and to examine racial/ethnic differences in quality of life, acceptability, adherence to, and lipoprotein response to the soy supplementation. The proposed study is a double blind, parallel group, randomized clinical trial. A total of 160 healthy postmenopausal women (50 percent African-American) with LDL cholesterol between 130 mg/dL and 190 mg/dL will be enrolled. Following a pre-randomization run-in period on a NCEP Step I diet, women will be randomized to receive soy containing isoflavones or casein dietary supplements for 3 months. Major outcome variables will be assessed in both groups at baseline and again at 3 months. It is hypothesized that soy supplementation will result in significantly greater reduction in LDL cholesterol, LDL particle concentration, and prevalence of dense LDL particles and improvement in menopausal quality of life compared with placebo and that these effects will be comparable in African-Americans and whites. This will be the first study to determine whether a natural plant product can ameliorate the unfavorable changes in known and novel lipid risk factors that are a consequence of menopause in both African-American and white women. The unique transitional outcomes explored in this study will add substantially to the limited body of knowledge of the effects of soy. Evaluation of this nutritional alternative to hormone replacement therapy (HRT) that may provide a beneficial effect on lipid risk factors and menopausal symptoms but would be free of the adverse effects on triglycerides, the breast and uterus, and thrombotic events associated with HRT could have significant public health implications for postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE EFFECT OF BLACK COHOSH EXTRACT ON THE HUMAN BREAST Principal Investigator & Institution: Sauter, Edward R.; Surgery; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Over 40 million women in the US have reached menopause, and 40% will experience symptoms significant enough to seek medical attention. Hormone replacement therapy, prescribed to ameliorate menopausal symptoms, has been associated with an increased risk of developing breast cancer. Many women use herbal preparations for menopausal complaints, believing them to be safe. Black cohosh extract (BCE) is the largest selling herbal dietary supplement in the United States used to alleviate menopausal symptoms. The mechanism of action by which BCE acts to treat menopausal symptoms of estrogen deficiency is not clear, with some data supporting a central nervous system effect, while other studies demonstrate a proestrogenic effect. The primary aim of this study is to determine if BCE administered to symptomatic postmenopausal women results in estrogenic stimulation of the breast as measured by changes in nipple aspirate fluid (NAF) levels of estradiol, pS2, follicle stimulating hormone (FSH), leutenizing hormone (LH) and prostate-specific antigen (PSA), as well as NAF cytology. Secondary aims are to 1) evaluate if BCE saponins, the proposed active constituents in BCE, are detectable in the NAF of women receiving BCE, 2) determine if BCE leads to a reduction in clinical symptoms of menopause, and 3) determine if the biomarker effects persist after stopping BCE. As the American population ages there are an increasing number of menopausal women. Interest in herbal therapies is rapidly growing among these women, including breast cancer survivors, to treat the disruptive symptoms associated with menopause. BCE binds to the estrogen receptor and in some studies stimulates breast cells. It is therefore important to demonstrate that BCE does not increase the risk of estrogen-related cancers. We have chosen biomarkers proven to be estrogen responsive proteins which are readily measured in both NAF and blood. Although prior studies failed to correlate clinical response to BCE with changes in serum levels of LH, FSH, or estradiol, it is critical to measure these markers in the breast itself, not diluted by the contribution from other organs. The findings should allow us to design a high quality R01 submission involving a larger, randomized study of longer duration which should provide some answers on the potential role of BCE in breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSGENIC MODELS OF ESTROGEN RECEPTOR ACTIVITY IN BONE Principal Investigator & Institution: Alexander, Joseph M.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 17-MAY-2002; Project End 30-APR-2005 Summary: The efficacy of hormone replacement therapy (HRT) in preventing postmenopausal bone loss is well-known. However, the relative roles of the two known estrogen receptors (ERs), alpha and beta, and their bone-specific mechanisms of action continue to be debated. For example, biochemical studies outlined below agree that ERalpha has profound inhibitory effects on osteoclast-mediated bone resorption by tonically down-regulating osteoblast cytokine production. Yet, recently reported 'double knock-out' mouse animal models for both ERalpha and ERbeta so far have shown no osteoporotic phenotype, despite clear effects of estrogen (E2)-deficiency in the uterus

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and gonads. The inability to reconcile data from in vitro cell culture experiments and the mouse double ERalpha/beta knockout studies have made it difficult to formulate a hypothesis regarding ER mechanism of action in bone. This is especially true since the established animal model for post-menopausal osteoporosis (OP)-the rat- is not yet accessible to genetic manipulation by transgenic and knock-out technologies. Thus, while the rat model can continue to test the efficacy of new therapies, it cannot be adapted to functionally characterize the molecular mechanisms of ERalpha and ERbeta action and their role in OP. In an effort to shed light on ERalpha and ERbeta function in bone, re report implementation of a mouse model of ovariectomy (OVX)-induced OP as a system for further elucidating the molecular mechanisms in hormone-dependent bone homeostasis. As a 'proof of principle' experiment for testing this model system, we propose to introduce characterized, constitutively action mutant ER alpha isoform (CAM-ERalpha) as transgenes into our mice. These two ERalpha isoforms, L536P and Y537S encode adjacent single residue changes in the ERalpha ligand-binding domain, and have been previously shown to confer full gene activation to ERalpha in the absence of E2 using in vitro cell-based assays. We will confirm the activity the CAM-ERalpha (L536P) and (Y537S) on MC-3T3-E1 osteoblastic cells. We then will determine whether these receptors can prevent bone loss in the absence of HRT in vivo by expressing CAMERalpha transgenes under the transcriptional control of an inducible 'Tet On/Off promoter system designed for regulating mammalian gene expression. If this pilot transgenic study demonstrates CAM-ERalpha isoforms can rescue the OP phenotype from OVX mice in the absence of HRT, it will be a key initial experiment in: 1) elucidating the molecular mechanisms of ERalpha in bone homeostasis in an in vivo assay, and 2) developing a mouse model system for OVX-induced OP that can be manipulated to add, delete, or alter specific gene targets that are active in bone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR REACTIVITY: GENDER AND HORMONAL INFLUENCE Principal Investigator & Institution: Duckles, Sue P.; Professor; Pharmacology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 30-JUN-2006 Summary: (provided by applicant): The recent explosion in understanding vascular effects of gonadal steroids includes identification of two types of estrogen receptor (ER) and both genomic and non-genomic mechanisms. Still, major questions remain concerning which receptors and which mechanisms contribute most to the actions of gonadal hormones. Therefore, we will continue to integrate both functional and biochemical approaches, using chronic hormone treatment in vivo to emphasize physiologically relevant effects in the cerebral circulation. The major hypothesis is: Estrogen and testosterone alter cerebrovascular function by influencing endothelial mechanisms. Cerebral arteries will be isolated from rats and mice chronically treated with gonadal steroids. Vascular contractility, endothelial calcium, smooth muscle membrane potential, synthetic proteins for vasoactive factors and their release will be quantified. Four specific hypotheses will be tested: 1. Estrogen, by activating ERalpha, increases endothelial-dependent cerebrovascular dilation. Estrogen may influence at least three vasodilators: NO, prostacyclin and endothelial derived hyperpolarizing factor (EDHF). We will test whether estrogen treatment increases vasodilation mediated by EDHF, whether there are significant interactions among endothelial factors that modulate estrogen effects, whether estrogen treatment increases endothelial calcium, and whether effects of estrogen on cerebrovascular endothelial function are mediated by genomic actions of ERalpha. 2. Testosterone increases cerebrovascular constriction

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through endothelial-dependent mechanisms. Since testosterone treatment increases cerebrovascular constriction, we will test whether testosterone affects endothelial vasoconstrictor and/or vasodilator factors. 3. Induction of COX-2 or iNOS will be altered by estrogen or testosterone. We will monitor iNOS and COX-2 induction and determine if gonadal steroids modulate inflammatory responses. 4. Progestins will modulate effects of estrogen. We will assess whether chronic progestin treatment alters vascular effects of estrogen. Given known sex differences in incidence of cardiovascular disease as well as the applicability of hormone replacement therapy to a large segment of the population, this work has tremendous significance for understanding physiological control of the cerebral circulation as well as improvement of hormonal therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WASHINGTON UNIVERSITY CLAUDE D PEPPER OAIC Principal Investigator & Institution: Holloszy, John O.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-AUG-2002 Summary: A major aim of the applicant's research over the past 20 years has been to determine the extent to which exercise-training can compensate for and/or partially reverse the deterioration in cardiovascular, neuromuscular, and metabolic functions and in physical performance capacities that occur with advancing age. As a result of this research, and that of others, there is, according to the applicant, now sufficient information regarding the beneficial effects of exercise in late middle- age and early oldage to justify promotion of exercise for maintenance of functional capacity in this age group. The applicant has, therefore, decided to focus the research of the OAIC on the question of whether or not physical frailty is reversible in old women and men at risk of losing their independence. There are two intervention studies (IS) in this OAIC. The goals of IS-1 are a) to determine the extent to which trail old women and men can respond to exercise training with the adaptations that have been shown to occur in younger individuals, and b) to assess whether the adaptations to exercise in the frail elderly are sufficiently large and functionally important to result in a significant reversal of frailty. The intervention in IS-1 is a 3-phase exercise program; the first phase consists of physical therapy exercises, the second consists of weight training exercises and the third consists of endurance exercise; the second and third phases will be superimposed on maintenance programs of the preceding types of exercise. The aim is to test the hypotheses that exercise can: a) increase functional capacity and reduce physical frailty; b) improve aerobic exercise capacity and/or cardiovascular function; c) induce a sufficient increase in muscle protein synthesis and/or decrease in muscle protein breakdown to result in increases in lean body and skeletal muscle mass; d) increase bone quantity and/or quality; and e) decrease insulin resistance, improve glucose tolerance, and improve lipid and lipoprotein levels. To the extent that it is feasible, the plan is to examine the mechanisms by which improvements in function are mediated. The interventions in IS-2 are hormone replacement therapy (HRT) and exercise superimposed on HRT. The goals of IS-2 are to determine whether a) HRT can bring about a reduction of frailty in physically frail old women, and b) exercise training results in greater improvements in functional capacity, muscle mass, cardiovascular function, and bone quantity and quality, in women who have been on HRT for 9-month than in sex hormone deficient women. The research of IS-1 and IS-2, and the pilot studies will be supported by five Research Resource Cores (RRC): Recruitment/Assessment/Health Services; Functional Assessment; Clinical Physiology/ Pathophysiology; Metabolic

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Function/Body Composition; and Biostatistics/Data Management. A long-term goal is to obtain information that can be used to design practical, individualized programs of exercise that can be utilized in community settings to prevent or reverse physical frailty and maintain functional independence. To translate findings from this research into health care practice, the Demonstration and Information Dissemination Core will disseminate research findings that are relevant to the prevention and reversal of frailty to the public and health care professionals. A major goal of the Research Development Core is to utilize the OAIC research activities and RRCs to train new investigators from a variety of disciplines to perform gerontological research relevant to the goals of the OAIC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

Changes in use of hormone replacement therapy after the report from the Women's Health Initiative: cross sectional survey of users. by Lawton B, Rose S, McLeod D, Dowell A.; 2003 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=214025

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Clinical practice guidelines for the care and treatment of breast cancer: 14. The role of hormone replacement therapy in women with a previous diagnosis of breast cancer. by Pritchard KI, Khan H, Levine M.; 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100875

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Combination hormone replacement therapy and dementia. by Wooltorton E.; 2003 Jul 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164982

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Effect of hormone replacement therapy on the pathological stage of breast cancer: population based, cross sectional study. by Stallard S, Litherland JC, Cordiner CM, Dobson HM, George WD, Mallon EA, Hole D.; 2000 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27281

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Ethnic differences in use of hormone replacement therapy: community based survey. by Harris TJ, Cook DG, Wicks PD, Cappuccio FP.; 1999 Sep 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28213

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

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

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Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomised trials. by Torgerson DJ, Bell-Syer SE.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59898

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Hormone replacement therapy and risk of hip fracture: population based case-control study. by Michaelsson K, Baron JA, Farahmand BY, Johnell O, Magnusson C, Persson PG, Persson I, Ljunghall S.; 1998 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28583

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Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1. by d'Elia HF, Mattsson LA, Ohlsson C, Nordborg E, Carlsten H.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165058

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Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women. by Lawson JS, Field AS, Tran DD, Houssami N.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57804

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Hormone replacement therapy: a time for pause. by Yusuf S, Anand S.; 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117850

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Postmenopausal hormone replacement therapy for chronic disease prevention: results from the Women's Health Initiative trial. by Farquhar D.; 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117857

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Pre-existing risk factor profiles in users and non-users of hormone replacement therapy: prospective cohort study in Gothenburg, Sweden. by Rodstrom K, Bengtsson C, Lissner L, Bjorkelund C.; 1999 Oct 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28245

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Randomised controlled trial of an interactive multimedia decision aid on hormone replacement therapy in primary care. by Murray E, Davis H, Tai SS, Coulter A, Gray A, Haines A.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=48137

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Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study. by Lokkegaard E, Pedersen AT, Heitmann BL, Jovanovic Z, Keiding N, Hundrup YA, Obel EB, Ottesen B.; 2003 Feb 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149444

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Risks and benefits of hormone replacement therapy: The evidence speaks. by Humphries KH, Gill S.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152685

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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

A common mutation in cholesteryl ester transfer protein gene and plasma HDL cholesterol level before and after hormone replacement therapy in Korean postmenopausal women. Author(s): Choi HS, Park JB, Han KO, Yim CH, Jung HY, Jang HC, Yoon HK, Cho DH, Shin HH, Han IK. Source: Korean J Intern Med. 2002 June; 17(2): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164095&dopt=Abstract

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A comparison of two different dosages of conjugated equine estrogen in continuous combined hormone replacement therapy with progestin. Author(s): Xing S, Wu Y, Liu J, Xu R, Zhang Z, Wang Y. Source: Chinese Medical Journal. 2003 April; 116(4): 584-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875727&dopt=Abstract

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A gynecologist's view of hormone replacement therapy in light of the Women's Health Initiative. Author(s): Jelovsek FR. Source: Southern Medical Journal. 2002 September; 95(9): 955-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356131&dopt=Abstract

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A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate. Author(s): Neven P, Lunde T, Benedetti-Panici P, Tiitinen A, Marinescu B, de Villiers T, Hillard T, Cano A, Peer E, Quail D, Nickelsen T; Eurolox 1 Study Group. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 February; 110(2): 157-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618160&dopt=Abstract

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A pilot study comparing the clinical effects of Jia-Wey Shiau-Yau San, a traditional Chinese herbal prescription, and a continuous combined hormone replacement therapy in postmenopausal women with climacteric symptoms. Author(s): Chen LC, Tsao YT, Yen KY, Chen YF, Chou MH, Lin MF. Source: Maturitas. 2003 January 30; 44(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568736&dopt=Abstract

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A randomised, double-blind trial comparing raloxifene HCl and continuous combined hormone replacement therapy in postmenopausal women: effects on compliance and quality of life. Author(s): Voss S, Quail D, Dawson A, Backstrom T, Aguas F, Erenus M, The HS, Bonnar J, De Geyter C, Hunter M, Nickelsen T; Euralox Investigators Group. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 August; 109(8): 874-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197366&dopt=Abstract

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A randomized, placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women. Author(s): Salobir BG, Keber I, Vrabic L. Source: Fertility and Sterility. 2002 December; 78(6): 1178-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477508&dopt=Abstract

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A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. Author(s): Clarke SC, Kelleher J, Lloyd-Jones H, Slack M, Schofiel PM. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 September; 109(9): 1056-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269682&dopt=Abstract

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Age, menopause and hormone replacement therapy influences on cardiovascular risk factors in a cohort of middle-aged Chilean women. Author(s): Castelo-Branco C, Blumel JE, Roncagliolo ME, Haya J, Bolf D, Binfa L, Tacla X, Colodron M. Source: Maturitas. 2003 July 25; 45(3): 205-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818466&dopt=Abstract

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Age-related eye diseases: impact of hormone replacement therapy, and reproductive and other risk factors,. by K. K. Snow and J. M. Seddon. Int J Fertil Womens Med 45:301-13, 2000. Author(s): Arroyo J. Source: Survey of Ophthalmology. 2003 March-April; 48(2): 236-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686310&dopt=Abstract

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Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Author(s): Ascott-Evans BH, Guanabens N, Kivinen S, Stuckey BG, Magaril CH, Vandormael K, Stych B, Melton ME. Source: Archives of Internal Medicine. 2003 April 14; 163(7): 789-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695269&dopt=Abstract

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An economic analysis of hormone replacement therapy for the prevention of fracture in young postmenopausal women. Author(s): Lamy O, Krieg MA, Burckhardt P, Wasserfallen JB. Source: Expert Opinion on Pharmacotherapy. 2003 September; 4(9): 1479-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943477&dopt=Abstract

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Angiotensin-converting enzyme gene polymorphism, lipids, and apolipoproteins in menopausal women on hormone replacement therapy. Author(s): Cubrilo-Turek M, Sertic J, Durakovic Z. Source: Acta Med Croatica. 2001; 55(4-5): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398019&dopt=Abstract

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Anti-aging medicine: part I. Hormone replacement therapy in women. Author(s): Kaweski S; Plastic Surgery Educational Foundation DATA Committee. Source: Plastic and Reconstructive Surgery. 2003 February; 111(2): 935-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560725&dopt=Abstract

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Antidiuretic hormone replacement therapy to prevent or ameliorate vasodilatory shock. Author(s): Singh Ranger G. Source: Medical Hypotheses. 2002 September; 59(3): 337-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208165&dopt=Abstract

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Are pharmacological considerations of relevance in hormone replacement therapy for prevention of chronic disease? Author(s): Lippert TH, Seeger H, Mueck AO. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 May; 23(3): 263-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850857&dopt=Abstract

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Are smoking-associated cancers prevented or postponed in women using hormone replacement therapy? Author(s): Olsson H, Bladstrom A, Ingvar C. Source: Obstetrics and Gynecology. 2003 September; 102(3): 565-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962944&dopt=Abstract

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Assessing benefits and harms of hormone replacement therapy: clinical applications. Author(s): Nelson HD. Source: Jama : the Journal of the American Medical Association. 2002 August 21; 288(7): 882-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186606&dopt=Abstract

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Association of hormone replacement therapy with bronchial hyper-responsiveness. Author(s): Mueller JE, Frye C, Brasche S, Heinrich J. Source: Respiratory Medicine. 2003 August; 97(8): 990-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924529&dopt=Abstract

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Attitude towards health and hormone replacement therapy among female obstetrician-gynecologists in Israel. Author(s): Kaplan B, Yogev Y, Sulkas J, Geva A, Nahum R, Fisher M. Source: Maturitas. 2002 October 25; 43(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385859&dopt=Abstract

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Basal leg blood flow in healthy women is related to age and hormone replacement therapy status. Author(s): Moreau KL, Donato AJ, Tanaka H, Jones PP, Gates PE, Seals DR. Source: The Journal of Physiology. 2003 February 15; 547(Pt 1): 309-16. Epub 2002 December 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562958&dopt=Abstract

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Bilateral carpal tunnel syndrome in a child on growth hormone replacement therapy: a case report. Author(s): Ong BC, Klugman JA, Jazrawi LM, Stutchin S. Source: Bull Hosp Jt Dis. 2001-2002; 60(2): 94-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003362&dopt=Abstract

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Bioequivalence and relative bioavailability of three estradiol and norethisterone acetate-containing hormone replacement therapy tablets. Author(s): Zdravkovic M, Muller M, Larsen S, Degenkolb J, Pabst G. Source: Int J Clin Pharmacol Ther. 2001 January; 39(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204938&dopt=Abstract

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Bioidentical hormone replacement therapy. A natural option for perimenopause and beyond. Author(s): Walker CR. Source: Adv Nurse Pract. 2001 May; 9(5): 39-42, 45. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400258&dopt=Abstract

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Bioidentical hormone replacement therapy. Customizing care for perimenopausal and menopausal women. Author(s): Romero M. Source: Adv Nurse Pract. 2002 November; 10(11): 47-8, 51-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478948&dopt=Abstract

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Biological effects of hormone replacement therapy in relation to serum estradiol levels. Author(s): Yasui T, Uemura H, Tezuka M, Yamada M, Irahara M, Miura M, Aono T. Source: Hormone Research. 2001; 56(1-2): 38-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815726&dopt=Abstract

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Bisphosphonate addition to stable hormone replacement therapy increases bone mineral density in postmenopausal women. Author(s): Boulos P, Sebaldt RJ, Goldsmith CH. Source: The Journal of Rheumatology. 2002 May; 29(5): 1110-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022339&dopt=Abstract

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Bleeding patterns in postmenopausal women using continuous combination hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate or with 17beta-estradiol and norethindrone acetate. Author(s): Odmark IS, Jonsson B, Backstrom T. Source: American Journal of Obstetrics and Gynecology. 2001 May; 184(6): 1131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349178&dopt=Abstract

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Blood pressure control and hormone replacement therapy in postmenopausal women at risk for coronary heart disease. Author(s): McCubbin JA, Helfer SG, Switzer FS 3rd, Price TM. Source: American Heart Journal. 2002 April; 143(4): 711-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923810&dopt=Abstract

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Body composition and quality of life as markers of the efficacy of growth hormone replacement therapy in adults. Author(s): Svensson J, Johannsson G, Bengtsson BA. Source: Hormone Research. 2001; 55 Suppl 2: 55-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684878&dopt=Abstract

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Body composition modulates the effects of hormone replacement therapy on growth hormone and insulin-like growth factor-I levels in postmenopausal women. Author(s): Figueroa A, Going SB, Milliken LA, Blew R, Sharp S, Lohman TG. Source: Gynecologic and Obstetric Investigation. 2002; 54(4): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592062&dopt=Abstract

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Bone mass response to discontinuation of long-term hormone replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study. Author(s): Greendale GA, Espeland M, Slone S, Marcus R, Barrett-Connor E; PEPI Safety Follow-Up Study (PSFS) Investigators. Source: Archives of Internal Medicine. 2002 March 25; 162(6): 665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911720&dopt=Abstract

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Bone-resorbing cytokines from peripheral blood mononuclear cells after hormone replacement therapy: a longitudinal study. Author(s): Bernard-Poenaru O, Roux C, Blanque R, Gardner C, de Vemejoul MC, Cohen-Solal ME. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(9): 769-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605744&dopt=Abstract

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Breast and pelvic examination in women taking hormone replacement therapy. Author(s): Harrison-Woolrych M, Purdie D. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2001 December; 108(12): 1201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843380&dopt=Abstract

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Breast cancer survival and hormone replacement therapy: a cohort analysis. Author(s): DiSaia PJ, Brewster WR, Ziogas A, Anton-Culver H. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2000 December; 23(6): 541-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202792&dopt=Abstract

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British-Asian women's views on and attitudes towards menopause and hormone replacement therapy. Author(s): Sethi K, Pitkin J. Source: Climacteric : the Journal of the International Menopause Society. 2000 December; 3(4): 248-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910584&dopt=Abstract

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By the way, doctor. I noticed that you listed Crinone, a vaginal progesterone, in one of your articles on products for hormone replacement therapy. Does it really offer as much protection against endometrial cancer as oral progestogens do? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 1999 December; 7(4): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10564965&dopt=Abstract

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By the way, doctor. I'm one year into menopause and really bothered by hot flashes and vaginal dryness. I'd like to take hormone replacement therapy, but I'm worried about increasing my risk of getting breast cancer. My doctor said I can take HRT at a dose longer than what's usually prescribed. What do you think? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 September; 9(1): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572838&dopt=Abstract

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By the way, Doctor. I've seen advertisements for red clover as a treatment for menopausal symptoms. Is it an effective alternative to hormone replacement therapy (HRT)? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 December; 9(5): 7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751101&dopt=Abstract

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By the way, Doctor. Whenever I read about the effects of hormone replacement therapy (HRT), the researchers always seem to use 0.625 mg of Premarin. I'm taking 1 mg of Estrace daily. How does this compare to the standard dose of Premarin? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 December; 9(5): 7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751102&dopt=Abstract

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Can a healthy endothelium influence the cardiovascular effects of hormone replacement therapy? Author(s): Koh KK. Source: International Journal of Cardiology. 2003 January; 87(1): 1-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468049&dopt=Abstract

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Cancer recurrence and mortality in women using hormone replacement therapy: meta-analysis. Author(s): Meurer LN, Lena S. Source: The Journal of Family Practice. 2002 December; 51(12): 1056-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540332&dopt=Abstract

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Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised, placebo-controlled, doubleblind study. Author(s): Sneppen SB, Steensgaard-Hansen F, Feldt-Rasmussen U. Source: Hormone Research. 2002; 58(1): 21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169777&dopt=Abstract

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Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index. Author(s): Mouritzen U, Christgau S, Lehmann HJ, Tanko LB, Christiansen C. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 332-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634232&dopt=Abstract

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Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women. Author(s): Cheng S, Sipila S, Taaffe DR, Puolakka J, Suominen H. Source: Bone. 2002 July; 31(1): 126-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110425&dopt=Abstract

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Changes in use of hormone replacement therapy after the report from the Women's Health Initiative: cross sectional survey of users. Author(s): Lawton B, Rose S, McLeod D, Dowell A. Source: Bmj (Clinical Research Ed.). 2003 October 11; 327(7419): 845-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551101&dopt=Abstract

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Changes in vaginal cytology after various types of hormone replacement therapy, according to body mass index and body fat distribution in postmenopausal women. Author(s): Carranza-Lira S, Barraza-Solorzano M, Fernandez RL. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 August; 78(2): 167-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175722&dopt=Abstract

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Climacteric symptoms and knowledge about hormone replacement therapy among Hong Kong Chinese women aged 40-60 years. Author(s): Lam PM, Leung TN, Haines C, Chung TK. Source: Maturitas. 2003 June 30; 45(2): 99-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787968&dopt=Abstract

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Clinical and personal relationships between oral contraceptive and hormone replacement therapy use among US women physicians. Author(s): Frank E, Elon L. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 133-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627038&dopt=Abstract

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Clinical assessment and quality of life of postmenopausal women treated with a new intermittent progestogen combination hormone replacement therapy: a placebocontrolled study. Author(s): Gelfand MM, Moreau M, Ayotte NJ, Hilditch JR, Wong BA, Lau CY. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 29-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544674&dopt=Abstract

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Clinical cardiovascular studies of hormone replacement therapy. Author(s): Collins P. Source: The American Journal of Cardiology. 2002 July 3; 90(1A): 30F-34F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106638&dopt=Abstract

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Combination hormone replacement therapy and dementia. Author(s): Wooltorton E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 July 22; 169(2): 133. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874164&dopt=Abstract

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Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Author(s): de Lignieres B, de Vathaire F, Fournier S, Urbinelli R, Allaert F, Le MG, Kuttenn F. Source: Climacteric : the Journal of the International Menopause Society. 2002 December; 5(4): 332-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626212&dopt=Abstract

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Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. Author(s): Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 259-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711012&dopt=Abstract

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Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Author(s): Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan AS, Haines CJ, Chan TY, Li M, Sham A. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 352-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851519&dopt=Abstract

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Comparison of the difference in histopathology and cell cycle kinetics among the postmenopausal endometrium treated with different progestins in sequentialcombined hormone replacement therapy. Author(s): Chang TC, Chen M, Lien YR, Chen RJ, Chow SN. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 172-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627044&dopt=Abstract

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Compliance with hormone replacement therapy in Thai women. Author(s): Manonai J, Theppisai U, Suchartwatnachai C, Jetsawangsri T, Chittacharoen A. Source: Maturitas. 2003 March 28; 44(3): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648883&dopt=Abstract

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Continuation of hormone replacement therapy after hysterectomy. Author(s): Domoney C, Studd JW, Mocroft A. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 58-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725666&dopt=Abstract

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Cost-effectiveness of hormone replacement therapy for fracture prevention in young postmenopausal women: an economic analysis based on a prospective cohort study. Author(s): Fleurence R, Torgerson DJ, Reid DM. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181622&dopt=Abstract

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Current attitudes toward hormone replacement therapy (HRT) prescribed during menopause. Author(s): Kaplan B. Source: Clin Exp Obstet Gynecol. 2002; 29(3): 167-71. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519035&dopt=Abstract

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Decisions about hormone replacement therapy. Whose responsibility are they? Author(s): Legare F, O'Connor A. Source: Can Fam Physician. 2003 February; 49: 132-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619731&dopt=Abstract

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Description of women's personality traits and psychological vulnerability prior to choosing hormone replacement therapy. Author(s): Loekkegaard E, Eplov LF, Koster A, Garde K. Source: Archives of Women's Mental Health. 2002 August; 5(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503071&dopt=Abstract

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Design and conduct of clinical trials in hormone replacement therapy. Author(s): Holinka CF. Source: Annals of the New York Academy of Sciences. 2001 September; 943: 89-108. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594562&dopt=Abstract

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Designer estrogen vs. hormone replacement therapy: the menopausal woman's dilemma. Author(s): Lappe JM. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 2001 JulyAugust; 20(4): 66-72; Quiz 72-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025675&dopt=Abstract

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Determinants of hormone replacement therapy duration among postmenopausal women with intact uteri. Author(s): Gavin NI, Thorp JM, Ohsfeldt RL. Source: Menopause (New York, N.Y.). 2001 September-October; 8(5): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528366&dopt=Abstract

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Developments in the management of menopause and hormone replacement therapy: a presentation given at the symposium to honour the retirement of Professor Martin Vessey. Author(s): Barlow DH. Source: Pharmacoepidemiology and Drug Safety. 2001 January-February; 10(1): 29-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417063&dopt=Abstract

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Differences in hormone replacement therapy use by social class, region and psychological symptoms. Author(s): Shah S, Harris TJ, Cook DG. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2001 March; 108(3): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281467&dopt=Abstract

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Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. Author(s): Nickelsen T, Creatsas G, Rechberger T, Depypere H, Erenus M, Quail D, Arndt T, Bonnar J; Euralox 1 Study Group. Source: Climacteric : the Journal of the International Menopause Society. 2001 December; 4(4): 320-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770189&dopt=Abstract

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Differing effects of oral and transdermal hormone replacement therapy on cardiovascular risk factors in healthy postmenopausal women. Author(s): Strandberg TE, Ylikorkala O, Tikkanen MJ. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 212-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860228&dopt=Abstract

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Discussing breast cancer and hormone replacement therapy with women. Author(s): Batur P, Thacker HL, Moore HC. Source: Cleve Clin J Med. 2002 November; 69(11): 838, 840, 843-4 Passim. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430969&dopt=Abstract

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Disparities in hormone replacement therapy use by socioeconomic status in a primary care population. Author(s): Finley C, Gregg EW, Solomon LJ, Gay E. Source: Journal of Community Health. 2001 February; 26(1): 39-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297189&dopt=Abstract

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Diurnal variation in uterine artery blood flow in post-menopausal women on oestrogen hormone replacement therapy. Author(s): Jurkovic D, Ross D, Aslam N, Whitehead M. Source: Human Reproduction (Oxford, England). 1999 November; 14(11): 2716-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548607&dopt=Abstract

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Does a better grade of tumour occurring in women under hormone replacement therapy compensate for their lower probability of detection by screening mammography. Author(s): Esteve J, Seradour B, Jacquemier J, Remontet L. Source: Journal of Medical Screening. 2002; 9(2): 70-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133926&dopt=Abstract

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Does blood pressure differ between users and non-users of hormone replacement therapy? The Women's Health In the Lund Area (WHILA) Study. Author(s): Enstrom I, Lidfeldt J, Lindholm LH, Nerbrand C, Pennert K, Samsioe G. Source: Blood Pressure. 2002; 11(4): 240-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361193&dopt=Abstract

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Does female gender or hormone replacement therapy affect early or late outcome after carotid endarterectomy? Author(s): Lane JS, Shekherdimian S, Moore WS. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 March; 37(3): 568-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618694&dopt=Abstract

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Does former use of hormonal contraception predispose women to accept hormone replacement therapy? Author(s): Maamari R. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2001 November 9; 3(6): 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965198&dopt=Abstract

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Does hormone replacement therapy (HRT) improve cognitive function or either delay or prevent dementia in postmenopausal women? Author(s): Dunne L, Seaton TL. Source: The Journal of Family Practice. 2001 June; 50(6): 547. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401745&dopt=Abstract

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Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign. Author(s): Gayet A, Esteve J, Seradour B, Piana L, Jacquemier J. Source: European Journal of Cancer (Oxford, England : 1990). 2003 August; 39(12): 173845. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888369&dopt=Abstract

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Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer? Author(s): Ursin G, Tseng CC, Paganini-Hill A, Enger S, Wan PC, Formenti S, Pike MC, Ross RK. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 February 1; 20(3): 699-706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821451&dopt=Abstract

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Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women? Author(s): Niskanen L, Laitinen T, Tuppurainen M, Saarikoski S, Kroger H, Alhava E, Hartikainen J. Source: Menopause (New York, N.Y.). 2002 January-February; 9(1): 52-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791086&dopt=Abstract

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Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause. Author(s): Zacharieva S, Shigarminova R, Nachev E, Kamenov Z, Atanassova I, Orbetzova M, Stoynev A, Doncheva N, Borissova AM. Source: Methods Find Exp Clin Pharmacol. 2003 April; 25(3): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743626&dopt=Abstract

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Effect of hormone replacement therapy on cardiovascular disease: current opinion. Author(s): Khan NS, Malhotra S. Source: Expert Opinion on Pharmacotherapy. 2003 May; 4(5): 667-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739992&dopt=Abstract

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Effect of hormone replacement therapy on lacrimal fluid peroxidase activity in woman. Author(s): Marcozzi G, Liberati V, Madia F, Pizzinga A, de Feo G. Source: Maturitas. 2003 July 25; 45(3): 225-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818468&dopt=Abstract

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Effect of hormone replacement therapy on plasma levels of the cardiovascular risk factor asymmetric dimethylarginine: a randomized, placebo-controlled 12-week study in healthy early postmenopausal women. Author(s): Post MS, Verhoeven MO, van der Mooren MJ, Kenemans P, Stehouwer CD, Teerlink T. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970290&dopt=Abstract

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Effect of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to myeloperoxidase promoter polymorphism. Author(s): Makela R, Dastidar P, Jokela H, Saarela M, Punnonen R, Lehtimaki T. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3823-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915675&dopt=Abstract

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Effect of neighborhood social participation on individual use of hormone replacement therapy and antihypertensive medication: a multilevel analysis. Author(s): Merlo J, Lynch JW, Yang M, Lindstrom M, Ostergren PO, Rasmusen NK, Rastam L. Source: American Journal of Epidemiology. 2003 May 1; 157(9): 774-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727671&dopt=Abstract

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Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy. Author(s): Going S, Lohman T, Houtkooper L, Metcalfe L, Flint-Wagner H, Blew R, Stanford V, Cussler E, Martin J, Teixeira P, Harris M, Milliken L, Figueroa-Galvez A, Weber J. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 August; 14(8): 637-43. Epub 2003 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844212&dopt=Abstract

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Effects of exercise training added to ongoing hormone replacement therapy on bone mineral density in frail elderly women. Author(s): Villareal DT, Binder EF, Yarasheski KE, Williams DB, Brown M, Sinacore DR, Kohrt WM. Source: Journal of the American Geriatrics Society. 2003 July; 51(7): 985-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834519&dopt=Abstract

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Effects of exercise training and hormone replacement therapy on lean and fat mass in postmenopausal women. Author(s): Figueroa A, Going SB, Milliken LA, Blew RM, Sharp S, Teixeira PJ, Lohman TG. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 March; 58(3): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634293&dopt=Abstract

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Effects of hormone replacement therapy on mammographic findings. Author(s): Bulbul NH, Ozden S, Dayicioglu V. Source: Archives of Gynecology and Obstetrics. 2003 April; 268(1): 5-8. Epub 2002 June 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673467&dopt=Abstract

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Effects of hormone replacement therapy on platelet activation in postmenopausal women. Author(s): Gu J, Yang D, Wang L, Yin S, Kuang J. Source: Chinese Medical Journal. 2003 August; 116(8): 1134-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12935396&dopt=Abstract

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Effects of hormone replacement therapy on serum angiotensin-converting enzyme activity and plasma bradykinin in postmenopausal women according to angiotensinconverting enzyme-genotype. Author(s): Sumino H, Ichikawa S, Ohyama Y, Nakamura T, Kanda T, Sakamoto H, Sakamaki T, Mizunuma H, Kurabayashi M. Source: Hypertens Res. 2003 January; 26(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661913&dopt=Abstract

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Effects of hormone replacement therapy on the sympathetic nervous system and blood pressure. Author(s): Wyss JM, Carlson SH. Source: Current Hypertension Reports. 2003 June; 5(3): 241-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724057&dopt=Abstract

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Effects of hormone replacement therapy on weight, abdominal fat distribution, and lipid levels in Japanese postmenopausal women. Author(s): Sumino H, Ichikawa S, Yoshida A, Murakami M, Kanda T, Mizunuma H, Sakamaki T, Kurabayashi M. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 September; 27(9): 1044-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917709&dopt=Abstract

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Effects of long-term estrogen replacement therapy versus combined hormone replacement therapy on nitric oxide-dependent vasomotor function. Author(s): Jokela H, Dastidar P, Rontu R, Salomaki A, Teisala K, Lehtimaki T, Punnonen R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4348-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970309&dopt=Abstract

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Effects of postmenopausal hormone replacement therapy on HbA(1c) levels. Author(s): Okada M, Nomura S, Ikoma Y, Yamamoto E, Ito T, Mitsui T, Tamakoshi K, Mizutani S. Source: Diabetes Care. 2003 April; 26(4): 1088-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663578&dopt=Abstract

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Effects of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy: a pilot study. Author(s): Pinto AB, A, Binder EF, Kohrt WM, Bronder DR, Williams DB. Source: American Journal of Obstetrics and Gynecology. 2003 July; 189(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861131&dopt=Abstract

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ER-alpha variants and the cardiovascular effects of hormone replacement therapy. Author(s): Herrington DM, Howard TD. Source: Pharmacogenomics. 2003 May; 4(3): 269-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718718&dopt=Abstract

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Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women. Author(s): Hamada AL, Maruo T, Samoto T, Yoshida S, Nash H, Spitz IM, Johansson E. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2003 June; 17(3): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857433&dopt=Abstract

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Etidronate and hormone replacement therapy (HRT) for postmenopausal women with osteoporosis despite HRT. Author(s): Morishige K, Yamamoto T, Sawada K, Ohmichi M, Tasaka K, Murata Y. Source: Archives of Gynecology and Obstetrics. 2003 June; 268(2): 105-6. Epub 2002 August 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768299&dopt=Abstract

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Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Author(s): Herrington DM, Vittinghoff E, Howard TD, Major DA, Owen J, Reboussin DM, Bowden D, Bittner V, Simon JA, Grady D, Hulley SB. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 June 1; 22(6): 1012-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067913&dopt=Abstract

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Factors affecting a woman's intent to adopt hormone replacement therapy for menopause. Author(s): Wilhelm SL. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2002 November-December; 31(6): 698-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465866&dopt=Abstract

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Factors affecting long-term adherence to hormone replacement therapy after screening for osteoporosis. Author(s): Steel SA, Albertazzi P, Howarth EM, Purdie DW. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 96-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841879&dopt=Abstract

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Factors associated with climacteric symptoms and the use of hormone replacement therapy. Author(s): Stadberg E, Mattsson LA, Milsom I. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 April; 79(4): 286-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10746844&dopt=Abstract

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Factors associated with endometrial bleeding in continuous hormone replacement therapy. Author(s): Shau WY, Hsieh CC, Hsieh TT, Hung TH, Huang KE. Source: Menopause (New York, N.Y.). 2002 May-June; 9(3): 188-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973442&dopt=Abstract

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Factors determining the use of hormone replacement therapy in recent naturally postmenopausal women participating in the French SU.VI.MAX cohort. Author(s): Mohammed-Cherif S, Briancon S, Potier de Courcy G, Preziosi P, Fieux B, Zarebska M, Galan P, Hercberg S. Source: European Journal of Epidemiology. 2000 May; 16(5): 477-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997836&dopt=Abstract

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Factors of risk for breast cancer influencing post-menopausal long-term hormone replacement therapy. Author(s): Chiechi LM, Secreto G. Source: Tumori. 2000 January-February; 86(1): 12-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10778760&dopt=Abstract

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Factors predicting current use of hormone replacement therapy among menopausal Jewish women in Israel. The National Women's Health Interview Survey, 1998. Author(s): Merom D, Ifrah A, Cohen-Manheim I, Chinich A, Green MS. Source: Isr Med Assoc J. 2002 September; 4(9): 671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440227&dopt=Abstract

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Female sex hormone replacement therapy increases serum free 1,25-dihydroxyvitamin D3: a 1-year prospective study. Author(s): van Hoof HJ, van der Mooren MJ, Swinkels LM, Sweep CG, Merkus JM, Benraad TJ. Source: Clinical Endocrinology. 1999 April; 50(4): 511-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468912&dopt=Abstract

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Fibrinolysis and lipoprotein(a) in women with coronary artery disease. Influence of hormone replacement therapy. Author(s): Falco C, Tormo G, Estelles A, Espana F, Tormo E, Gilabert J, Velasco JA, Aznar J. Source: Haematologica. 2001 January; 86(1): 92-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11146577&dopt=Abstract

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Five years of growth hormone replacement therapy in adults: age- and gender-related changes in isometric and isokinetic muscle strength. Author(s): Svensson J, Stibrant Sunnerhagen K, Johannsson G. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 May; 88(5): 2061-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727955&dopt=Abstract

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Five-year compliance with hormone replacement therapy in postmenopausal Chinese women in Hong Kong. Author(s): Leung TN, Haines CJ, Chung TK. Source: Maturitas. 2001 September 28; 39(3): 195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574178&dopt=Abstract

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Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Author(s): Lemay A, Dodin S, Kadri N, Jacques H, Forest JC. Source: Obstetrics and Gynecology. 2002 September; 100(3): 495-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220769&dopt=Abstract

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Flow resistance in carotid and middle cerebral arteries in postmenopausal women: a comparative study of tibolone and continuous combined hormone replacement therapy. Author(s): Pan HA, Wang ST, Chen CH, Pai MC, Wu MH, Huang KE. Source: Climacteric : the Journal of the International Menopause Society. 2002 September; 5(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419084&dopt=Abstract

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Fluctuations of lipid and lipoprotein levels in hyperlipidemic postmenopausal women receiving hormone replacement therapy. Author(s): Weintraub MS, Grosskopf I, Charach G, Eckstein N, Ringel Y, Maharshak N, Rotmensch HH, Rubinstein A. Source: Archives of Internal Medicine. 1998 September 14; 158(16): 1803-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9738610&dopt=Abstract

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Focus on cardiovascular health: hormone replacement therapy, estrogen replacement therapy, and selective estrogen receptor modulators. Author(s): Walsh BW. Source: J Am Osteopath Assoc. 2003 February; 103(2 Suppl 2): S6-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625632&dopt=Abstract

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Follow-up study of the benefits of hormone replacement therapy on isometric muscle strength of adductor pollicis in postmenopausal women. Author(s): Onambele NG, Skelton DA, Bruce SA, Woledge RC. Source: Clinical Science (London, England : 1979). 2001 April; 100(4): 421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256982&dopt=Abstract

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Fractal analysis of trabecular bone texture on calcaneus radiographs: effects of age, time since menopause and hormone replacement therapy. Author(s): Lespessailles E, Poupon S, Niamane R, Loiseau-Peres S, Derommelaere G, Harba R, Courteix D, Benhamou CL. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 May; 13(5): 366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086346&dopt=Abstract

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Frail older women's participation in a trial of hormone replacement therapy: perceived benefits and concerns. Author(s): Jeffe DB, Binder EF, Williams DB, Kohrt WM. Source: Menopause (New York, N.Y.). 2001 Summer; 8(2): 127-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256873&dopt=Abstract

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Gauging the benefits, risks, and unknowns of hormone replacement therapy. Exploring HRT. Author(s): Valerie AM. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2002 February-March; 6(1): 24-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913199&dopt=Abstract

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General and medical factors associated with hormone replacement therapy among women attending menopause clinics in Italy. Author(s): Progetto Menopausa Italia Study Group. Source: Menopause (New York, N.Y.). 2001 July-August; 8(4): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449088&dopt=Abstract

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Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study. Author(s): Fineberg SE. Source: Drugs & Aging. 2000 December; 17(6): 453-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200306&dopt=Abstract

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Glycaemic control and plasma lipoproteins in menopausal women with Type 2 diabetes treated with oral and transdermal combined hormone replacement therapy. Author(s): Darko DA, Dornhorst A, Kennedy G, Mandeno RC, Seed M. Source: Diabetes Research and Clinical Practice. 2001 December; 54(3): 157-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689270&dopt=Abstract

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GnRH analogues and uterine leiomyomas. Effect of hormone replacement therapy on cell proliferation. Author(s): Rintala S, Kujansuu E, Teisala K, Rantala I, Kivinen S, Tuimala R. Source: Gynecologic and Obstetric Investigation. 1999; 48(4): 276-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10592433&dopt=Abstract

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Gonadotropin-releasing hormone agonist plus “add-back” hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebocontrolled, double-blind trial. Author(s): Franke HR, van de Weijer PH, Pennings TM, van der Mooren MJ. Source: Fertility and Sterility. 2000 September; 74(3): 534-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10973651&dopt=Abstract

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Growth hormone replacement therapy (GHRT) in children and adolescents: skeletal impact. Author(s): Mukherjee A, Shalet SM. Source: Medical and Pediatric Oncology. 2003 September; 41(3): 235-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868125&dopt=Abstract

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Growth hormone replacement therapy and insulin sensitivity. Author(s): Svensson J, Bengtsson BA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 1453-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679421&dopt=Abstract

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Growth hormone replacement therapy during transition of patients with childhoodonset growth hormone deficiency into adulthood: what are the issues? Author(s): Shalet SM, Rosenfeld RG. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 1998 April; 8 Suppl B: 17784. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10990158&dopt=Abstract

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Growth hormone replacement therapy for adults: into the new millennium. Author(s): Simpson H, Savine R, Sonksen P, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Cohen P, Hintz R, Ho K, Mullis P, Robinson I, Strasburger C, Tanaka T, Thorner M; GRS Council. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2002 February; 12(1): 1-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127299&dopt=Abstract

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Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. Author(s): Fernholm R, Bramnert M, Hagg E, Hilding A, Baylink DJ, Mohan S, Thoren M. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 November; 85(11): 4104-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095440&dopt=Abstract

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Growth hormone replacement therapy in adults with growth hormone deficiency improves vascular reactivity. Author(s): Christ ER, Chowienczyk PJ, Sonksen PH, Russel-Jones DL. Source: Clinical Endocrinology. 1999 July; 51(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468961&dopt=Abstract

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Growth hormone replacement therapy in children with leukemia in remission. Author(s): Taha DR, Bastian W, Castells S. Source: Clinical Pediatrics. 2001 August; 40(8): 441-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516051&dopt=Abstract

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Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. Author(s): Packer RJ, Boyett JM, Janss AJ, Stavrou T, Kun L, Wisoff J, Russo C, Geyer R, Phillips P, Kieran M, Greenberg M, Goldman S, Hyder D, Heideman R, Jones-Wallace D, August GP, Smith SH, Moshang T. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 January 15; 19(2): 480-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208842&dopt=Abstract

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Growth hormone replacement therapy induces codeine clearance. Author(s): Gil Berglund E, Johannsson G, Beck O, Bengtsson BA, Rane A. Source: European Journal of Clinical Investigation. 2002 July; 32(7): 507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153551&dopt=Abstract

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Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle. Author(s): Bramnert M, Segerlantz M, Laurila E, Daugaard JR, Manhem P, Groop L. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 145563. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679422&dopt=Abstract

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Growth hormone replacement therapy is not associated with any increase in mortality. KIMS Study Group. Author(s): Bengtsson BA, Koppeschaar HP, Abs R, Bennmarker H, Hernberg-Stahl E, Westberg B, Wilton P, Monson JP, Feldt-Rasmussen U, Wuster C. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 November; 84(11): 4291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566688&dopt=Abstract

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Growth hormone replacement therapy is not associated with retinal changes. Author(s): Blank D, Riedl M, Reitner A, Schnack C, Schernthaner G, Clodi M, Frisch H, Luger A. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 February; 85(2): 634-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10690868&dopt=Abstract

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Guidelines advise against hormone replacement therapy for cardiovascular disease prevention. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2001 August 23; 12(17): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296365&dopt=Abstract

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 354-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218724&dopt=Abstract

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Hormone replacement therapy after treatment for breast cancer: physicians' attitudes towards randomized trials. Author(s): Del Giudice ME, Sawka CA, Pritchard KI, Llewellyn-Thomas HA, Trudeau ME, Lewis JE, Franssen E. Source: Breast Cancer Research and Treatment. 2003 May; 79(2): 213-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825856&dopt=Abstract

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Hormone replacement therapy and autonomic cardiovascular functions: the impact of heart rate variability analyses methods. Author(s): Kaya D. Source: American Journal of Obstetrics and Gynecology. 2003 September; 189(3): 896; Author Reply 896-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560748&dopt=Abstract

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Hormone replacement therapy and health protection. Author(s): Chiechi LM. Source: Curr Opin Investig Drugs. 2003 April; 4(4): 439-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808884&dopt=Abstract

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Hormone replacement therapy and hypercoagulability. Results from the Prospective Collaborative Danish Climacteric Study. Author(s): Sidelmann JJ, Jespersen J, Andersen LF, Skouby SO; Prospective Collaborative Danish Climacteric Study. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 June; 110(6): 541-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798469&dopt=Abstract

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Hormone replacement therapy and inflammation: interactions in cardiovascular disease. Author(s): Miller AP, Chen YF, Xing D, Feng W, Oparil S. Source: Hypertension. 2003 October; 42(4): 657-63. Epub 2003 August 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913055&dopt=Abstract

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Hormone replacement therapy and menopause: a review of randomized, doubleblind, placebo-controlled trials. Author(s): Chang C, Lin CH. Source: Kaohsiung J Med Sci. 2003 June; 19(6): 257-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873034&dopt=Abstract

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Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study. Author(s): Rea TD, Psaty BM, Heckbert SR, Cushman M, Meilahn E, Olson JL, Lemaitre RN, Smith NL, Sotoodehnia N, Chaves PH. Source: Journal of Women's Health (2002). 2003 May; 12(4): 341-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804341&dopt=Abstract

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Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden. Author(s): Shah NR. Source: Cancer. 2003 October 1; 98(7): 1552-3; Author Reply 1553. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508845&dopt=Abstract

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Hormone replacement therapy for postmenopausal osteoporosis. Author(s): Cranney A, Wells GA. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 361-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916291&dopt=Abstract

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Hormone replacement therapy in postmenopausal women with benign fibrocystic mastopathy. Author(s): Yenen MC, Dede M, Goktolga U, Kucuk T, Pabuccu R. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841885&dopt=Abstract

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Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1. Author(s): D'Elia HF, Mattsson LA, Ohlsson C, Nordborg E, Carlsten H. Source: Arthritis Research & Therapy. 2003; 5(4): R202-9. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823855&dopt=Abstract

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Hormone replacement therapy in the post-Women's Health Initiative era. Report a a meeting held in Funchal, Madeira, February 24-25, 2003. Author(s): Burger H. Source: Climacteric : the Journal of the International Menopause Society. 2003 May; 6 Suppl 1: 11-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945798&dopt=Abstract

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Hormone replacement therapy is associated with improved survival in women with advanced heart failure. Author(s): Lindenfeld J, Ghali JK, Krause-Steinrauf HJ, Khan S, Adams K, Goldman S, Peberdy MA, Yancy C, Thaneemit-Chen S, Larsen RL, Young J, Lowes B, Rosenberg YD; BEST Investigators. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1238-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522488&dopt=Abstract

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Hormone replacement therapy. Author(s): Cheifitz RL. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 August; 93(8): 554-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531100&dopt=Abstract

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Hormone replacement therapy: attitude and acceptance of Bangkokian women. Author(s): Taechakraichana N, Wilawan K, Wipatavit V, Maitrisathit S, Thamanavat N, Jaisamrarn U, Panyakhamlerd K, Havanond P, Limpaphayom KK. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S385-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930015&dopt=Abstract

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Hormone replacement therapy: dilemmas in 2002. Author(s): Moore A. Source: Trans Am Clin Climatol Assoc. 2003; 114: 233-8; Discussion 238-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813923&dopt=Abstract

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Hormone replacement therapy: primary and secondary prevention. Author(s): Penckofer S, Schwertz D. Source: The Journal of Cardiovascular Nursing. 2001 April; 15(3): 1-25; Quiz 109-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968768&dopt=Abstract

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Hormone replacement therapy: prothrombotic vs. protective effects. Author(s): Lowe GD. Source: Pathophysiology of Haemostasis and Thrombosis. 2002 September-December; 32(5-6): 329-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509584&dopt=Abstract

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Hormone replacement therapy: to use or not to use? Author(s): Baber RJ, O'Hara JL, Boyle FM. Source: The Medical Journal of Australia. 2003 June 16; 178(12): 630-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797851&dopt=Abstract

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Hormone replacement therapy--is there a place for its use in neurology? Author(s): Vukovic V, Lovrencic-Huzjan A, Solter VV, Dordevic V, Demarin V. Source: Coll Antropol. 2003 June; 27(1): 413-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974172&dopt=Abstract

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Impact of hormone replacement therapy on endogenous estradiol metabolism in postmenopausal women. Author(s): Mueck AO, Seeger H, Wallwiener D. Source: Maturitas. 2002 October 25; 43(2): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385856&dopt=Abstract

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In search of the impossible dream? Thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients. Author(s): Kaplan MM, Sarne DH, Schneider AB. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 October; 88(10): 4540-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557418&dopt=Abstract

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Increased levels of C-reactive protein after oral hormone replacement therapy may not be related to an increased inflammatory response. Author(s): Silvestri A, Gebara O, Vitale C, Wajngarten M, Leonardo F, Ramires JA, Fini M, Mercuro G, Rosano GM. Source: Circulation. 2003 July 1; 107(25): 3165-9. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796135&dopt=Abstract

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Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women. Author(s): Post MS, Rosing J, Van Der Mooren MJ, Zweegman S, Van Baal WM, Kenemans P, Stehouwer CD; Ageing Women' and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU). Source: British Journal of Haematology. 2002 December; 119(4): 1017-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472583&dopt=Abstract

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Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Author(s): Carney PA, Miglioretti DL, Yankaskas BC, Kerlikowske K, Rosenberg R, Rutter CM, Geller BM, Abraham LA, Taplin SH, Dignan M, Cutter G, Ballard-Barbash R. Source: Annals of Internal Medicine. 2003 February 4; 138(3): 168-75. Erratum In: Ann Intern Med. 2003 May 6; 138(9): 771. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558355&dopt=Abstract

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Individualising hormone replacement therapy. Author(s): Attilakos G, Wardle PG. Source: The Practitioner. 2002 May; 246(1634): 295-8, 302, 305 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043347&dopt=Abstract

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Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study. Author(s): Pradhan AD, Manson JE, Rossouw JE, Siscovick DS, Mouton CP, Rifai N, Wallace RB, Jackson RD, Pettinger MB, Ridker PM. Source: Jama : the Journal of the American Medical Association. 2002 August 28; 288(8): 980-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190368&dopt=Abstract

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Influence of hormone replacement therapy on C-reactive protein: population-based data. Author(s): Primatesta P, Falaschetti E, Poulter NR. Source: Journal of Cardiovascular Risk. 2003 February; 10(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569237&dopt=Abstract

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Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis. Author(s): D'Elia HF, Larsen A, Mattsson LA, Waltbrand E, Kvist G, Mellstrom D, Saxne T, Ohlsson C, Nordborg E, Carlsten H. Source: The Journal of Rheumatology. 2003 July; 30(7): 1456-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858441&dopt=Abstract

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Influences of hormone replacement therapy on postmenopausal women's health perceptions. Author(s): Blumel JE, Castelo-Branco C, Kerrigan N, Cancelo MJ, Blumel B, Haya J, Flores M, Carvajal MC, Sarra S. Source: Menopause (New York, N.Y.). 2003 May-June; 10(3): 235-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792296&dopt=Abstract

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Inhibition of cytochrome P450 2B6 activity by hormone replacement therapy and oral contraceptive as measured by bupropion hydroxylation. Author(s): Palovaara S, Pelkonen O, Uusitalo J, Lundgren S, Laine K. Source: Clinical Pharmacology and Therapeutics. 2003 October; 74(4): 326-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534519&dopt=Abstract

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Interaction between hormone replacement therapy preparations and oral anticoagulant therapy. Author(s): McLintock LA, Dykes A, Tait RC, Walker ID. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 August; 110(8): 777-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892692&dopt=Abstract

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Intermittent progestin administration as part of hormone replacement therapy: longterm comparison between estradiol 1 mg combined with intermittent norgestimate and estradiol 2 mg combined with constant norethisterone acetate. Author(s): Ylikorkala O, Wahlstrom T, Caubel P, Lane R. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 July; 81(7): 654-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190841&dopt=Abstract

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Intranasal hormone replacement therapy. Author(s): Wattanakumtornkul S, Pinto AB, Williams DB. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 88-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544682&dopt=Abstract

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Intrauterine pathology in women with abnormal uterine bleeding taking hormone replacement therapy. Author(s): Leung PL, Tam WH, Kong WS, Yuen PM. Source: The Journal of the American Association of Gynecologic Laparoscopists. 2003 May; 10(2): 260-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732781&dopt=Abstract

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Introduction: the role of hormone replacement therapy in prevention and treatment of cardiovascular disease in postmenopausal women. Author(s): Mishell DR Jr, Mendelsohn ME. Source: The American Journal of Cardiology. 2002 June 20; 89(12A): 1E-4E. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084394&dopt=Abstract

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Is hormone replacement therapy associated with an increased risk of irritable bowel syndrome? Author(s): Ruigomez A, Garcia Rodriguez LA, Johansson S, Wallander MA. Source: Maturitas. 2003 February 25; 44(2): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590009&dopt=Abstract

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Is there any rationale for prescribing hormone replacement therapy (HRT) to prevent or to treat osteoarthritis? Author(s): Reginster JY, Kvasz A, Bruyere O, Henrotin Y. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 February; 11(2): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554124&dopt=Abstract

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Is use of hormone replacement therapy associated with increased detection of human papillomavirus and potential risk of HPV-related genital cancers? Author(s): Smith EM, Levy BT, Ritchie JM, Jia J, Wang D, Haugen TH, Turek LP. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2002 June; 11(3): 295-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131663&dopt=Abstract

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Issues of hormone replacement therapy and cardiovascular disease for elderly women. Author(s): Limacher MC. Source: The American Journal of Geriatric Cardiology. 2002 July-August; 11(4): 217-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091770&dopt=Abstract

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Knowledge of menopause and hormone replacement therapy use in low-income urban women. Author(s): Appling SE, Allen JK, Van Zandt S, Olsen S, Brager R, Hallerdin J. Source: Journal of Women's Health & Gender-Based Medicine. 2000 January-February; 9(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10718507&dopt=Abstract

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Knowledge, attitudes and management strategies in Scandinavia concerning hormone replacement therapy: a comparison between gynecologists in Denmark, Norway and Sweden. Author(s): Nilsen ST, Pedersen AT, Moen MH, Milsom I, Mattsson LA, Iversen OE, Larsen PM, Andersson K. Source: Maturitas. 2001 July 25; 39(1): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451625&dopt=Abstract

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Knowledge-attitude-practice of sexual intercourse of post-menopausal women using hormone replacement therapy. Author(s): Somboonporn W, Seejorn K, Kleebkaow P, Junthathamrongwat N, Ratanasiri T. Source: J Med Assoc Thai. 2002 February; 85(2): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081115&dopt=Abstract

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Landmark hormone replacement therapy study stopped after finding more harms than benefits. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2002 August 9; 13(15): 5-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553323&dopt=Abstract

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Lifestyle factors and choice of hormone replacement therapy among Danish nurses. Author(s): Hundrup YA, Thoning H, Obel EB, Rasmussen NK, Philip J. Source: Scandinavian Journal of Public Health. 2002; 30(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928833&dopt=Abstract

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Lipid and lipoprotein responses to oral combined hormone replacement therapy in normolipemic obese women with controlled type 2 diabetes mellitus. Author(s): Lilley SH, Spivey JM, Vadlamudi S, Otvos J, Cummings DM, Barakat H. Source: Journal of Clinical Pharmacology. 1998 December; 38(12): 1107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301562&dopt=Abstract

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Lipid profiles and endothelial function with low-dose hormone replacement therapy in postmenopausal women at risk for coronary artery disease: a randomized trial. Author(s): Mercuro G, Vitale C, Fini M, Zoncu S, Leonardo F, Rosano GM. Source: International Journal of Cardiology. 2003 June; 89(2-3): 257-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767550&dopt=Abstract

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Local and systemic options for hormone replacement therapy. Author(s): Gilliam ML. Source: Int J Fertil Womens Med. 2001 July-August; 46(4): 222-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563833&dopt=Abstract

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Long term-effects of hormone replacement therapy. Author(s): Subbiah MT. Source: Lancet. 2003 January 18; 361(9353): 255. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547559&dopt=Abstract

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Long term-effects of hormone replacement therapy. Author(s): Chan NN, Tong PC, Chow CC, Chan JC. Source: Lancet. 2003 January 18; 361(9353): 254; Author Reply 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547557&dopt=Abstract

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Longitudinal changes in weight in perimenopausal and early postmenopausal women: effects of dietary energy intake, energy expenditure, dietary calcium intake and hormone replacement therapy. Author(s): Macdonald HM, New SA, Campbell MK, Reid DM. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 June; 27(6): 669-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833110&dopt=Abstract

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Long-term continuous combined hormone replacement therapy in the prevention of postmenopausal bone loss: a comparison of high- and low-dose estrogen-progestin regimens. Author(s): Heikkinen J, Vaheri R, Kainulainen P, Timonen U. 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(11): 929-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11193245&dopt=Abstract

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Long-term effects of hormone replacement therapy on bone mineral density in girls oophorectomized in adolescence. Author(s): Kanaoka Y, Honda K, Ishiko O, Hirai K, Ogita S. Source: Gynecologic and Obstetric Investigation. 2003; 55(3): 168-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865597&dopt=Abstract

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Long-term effects of hormone replacement therapy. Author(s): Stevenson JC. Source: Lancet. 2003 January 18; 361(9353): 253-4; Author Reply 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547556&dopt=Abstract

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Long-term effects of oral and transdermal hormone replacement therapy on plasma homocysteine levels. Author(s): Chiantera V, Sarti CD, Fornaro F, Farzati A, De Franciscis P, Sepe E, Borrelli AL, Colacurci N. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851511&dopt=Abstract

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Long-term estrogen and hormone replacement therapy for the prevention and treatment of osteoporosis. Author(s): Levine JP. Source: Curr Womens Health Rep. 2003 June; 3(3): 181-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734027&dopt=Abstract

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Long-term growth hormone replacement therapy in hypopituitary adults. Author(s): Verhelst J, Abs R. Source: Drugs. 2002; 62(16): 2399-412. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396230&dopt=Abstract

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Long-term hormone replacement therapy in two patients with Kabuki syndrome and growth hormone deficiency. Author(s): Gabrielli O, Carloni I, Coppa GV, Bedeschi MF, Petroncini MM, Selicorni A. Source: Minerva Pediatr. 2000 January-February; 52(1-2): 47-53. English, Italian. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829592&dopt=Abstract

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Long-term use of estrogen-only hormone replacement therapy (HRT) linked with increased risk of ovarian cancer. Author(s): American Medical Association. Source: Ginecologia Y Obstetricia De Mexico. 2002 August; 70: 409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448047&dopt=Abstract

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Low incidence of endometrial hyperplasia with acceptable bleeding patterns in women taking sequential hormone replacement therapy with dydrogesterone. Author(s): Bergeron C, Fox H. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 August; 14(4): 275-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11075299&dopt=Abstract

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Low-dose hormone replacement therapy for hot flashes. Author(s): Mikhail N. Source: Mayo Clinic Proceedings. 2003 March; 78(3): 379; Author Reply 379. Erratum In: Mayo Clin Proc. 2003 May; 78(5): 656. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630592&dopt=Abstract

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Low-dose hormone replacement therapy: effects on bone. Author(s): Gambacciani M, Monteleone P, Genazzani AR. Source: Climacteric : the Journal of the International Menopause Society. 2002 June; 5(2): 135-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051108&dopt=Abstract

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Lower diabetes risk with hormone replacement therapy: an encore for estrogen? Author(s): Wilson PW. Source: Annals of Internal Medicine. 2003 January 7; 138(1): 69-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513048&dopt=Abstract

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Making decisions about hormone replacement therapy. Author(s): Rymer J, Wilson R, Ballard K. Source: Bmj (Clinical Research Ed.). 2003 February 8; 326(7384): 322-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574048&dopt=Abstract

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Making decisions about hormone replacement therapy: bisphosphonates should not be recommended for women aged 50. Author(s): Ott SM. Source: Bmj (Clinical Research Ed.). 2003 June 21; 326(7403): 1398; Author Reply 1398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816846&dopt=Abstract

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Making decisions about hormone replacement therapy: preparations containing oestrogen should not be given during treatment for breast cancer. Author(s): Hinton CP, Coventry C, Borrowclough B. Source: Bmj (Clinical Research Ed.). 2003 June 21; 326(7403): 1398; Author Reply 1398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816848&dopt=Abstract

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Medical issues and hormone replacement therapy. Author(s): Harris PF. Source: Curr Womens Health Rep. 2002 October; 2(5): 373-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215310&dopt=Abstract

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Menopausal hormone replacement therapy and risk of ovarian cancer. Author(s): Lacey JV Jr, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, Schatzkin A, Schairer C. Source: Jama : the Journal of the American Medical Association. 2002 July 17; 288(3): 334-41. Erratum In: Jama 2002 November 27; 288(20): 2544. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117398&dopt=Abstract

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Menopause, hormone replacement therapy and tear function. Author(s): Evans I, Millar TJ, Eden JA, Willcox MD. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1029-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614027&dopt=Abstract

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Message about hormone replacement therapy is unclear. Author(s): Dixon JM. Source: Bmj (Clinical Research Ed.). 2002 November 2; 325(7371): 1036. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411373&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Author(s): Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, Robinson V, Henry D, O'Connell D, Cranney A; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 529-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202468&dopt=Abstract

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Methods for evaluating the effects of new hormone replacement therapy compounds on coronary artery disease. Author(s): Ouyang P. Source: The American Journal of Cardiology. 2002 July 3; 90(1A): 44F-50F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106640&dopt=Abstract

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Monitoring hormone replacement therapy by biochemical markers of bone metabolism in menopausal women. Author(s): Dogan E, Posaci C. Source: Postgraduate Medical Journal. 2002 December; 78(926): 727-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509689&dopt=Abstract

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Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. An open-label pilot efficacy and safety study. Author(s): Ringe JD, Setnikar I. Source: Rheumatology International. 2002 May; 22(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120908&dopt=Abstract

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Naloxone decreases insulin secretion in hyperinsulinemic postmenopausal women and may positively affect hormone replacement therapy. Author(s): Cucinelli F, Soranna L, Perri C, Romualdi D, Barini A, Mancuso S, Lanzone A. Source: Fertility and Sterility. 2002 November; 78(5): 1017-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413987&dopt=Abstract

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National differences in lipid response to postmenopausal hormone replacement therapy. Author(s): Ranta V, Oksanen H, Arrenbrecht S, Ylikorkala O. Source: Maturitas. 2002 August 30; 42(4): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191848&dopt=Abstract

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Negative mood changes during hormone replacement therapy: a comparison between two progestogens. Author(s): Bjorn I, Bixo M, Nojd KS, Nyberg S, Backstrom T. Source: American Journal of Obstetrics and Gynecology. 2000 December; 183(6): 1419-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120505&dopt=Abstract

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Neither long-term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in healthy postmenopausal women: two randomized, placebo-controlled, 2-year studies. Author(s): Vogelvang TE, Mijatovic V, Kamp O, Netelenbos JC, Neele SJ, Pines A, Kenemans P, van der Mooren MJ. Source: American Journal of Obstetrics and Gynecology. 2002 April; 186(4): 729-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967499&dopt=Abstract

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Nicotine withdrawal and depressive symptomatology during short-term smoking abstinence: a comparison of postmenopausal women using and not using hormone replacement therapy. Author(s): Allen SS, Hatsukami DK, Christianson D. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745506&dopt=Abstract

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Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent. Author(s): Bjarnason NH, Alexandersen P, Christiansen C. Source: Bone. 2002 April; 30(4): 637-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934658&dopt=Abstract

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Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Author(s): Sorensen MB, Rosenfalck AM, Hojgaard L, Ottesen B. Source: Obesity Research. 2001 October; 9(10): 622-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595778&dopt=Abstract

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Observational studies and randomized trials of hormone replacement therapy: what can we learn from them? Author(s): Whittemore AS, McGuire V. Source: Epidemiology (Cambridge, Mass.). 2003 January; 14(1): 8-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500037&dopt=Abstract

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Opinion survey towards hormone replacement therapy in the prevention of coronary heart disease. Author(s): Rozenberg S, Fellemans C, Ham H. Source: Maturitas. 2001 May 30; 38(3): 273-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358644&dopt=Abstract

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Optimizing the dose of hormone replacement therapy. Author(s): Rice VM. Source: Int J Fertil Womens Med. 2002 September-October; 47(5): 205-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469707&dopt=Abstract

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Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Author(s): Vihtamaki T, Parantainen J, Koivisto AM, Metsa-Ketela T, Tuimala R. Source: Maturitas. 2002 June 25; 42(2): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065172&dopt=Abstract

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Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria. Author(s): Monster TB, Janssen WM, de Jong PE, de Jong-van den Berg LT; Prevention of Renal and Vascular End Stage Disease Study Group. Source: Archives of Internal Medicine. 2001 September 10; 161(16): 2000-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525702&dopt=Abstract

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Oral contraceptives, hormone replacement therapy and thrombosis. Author(s): Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Source: Thrombosis and Haemostasis. 2001 July; 86(1): 112-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486996&dopt=Abstract


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Oral hormone replacement therapy: factors that influence the estradiol concentrations achieved in a multiracial study population. Author(s): Gavaler JS. Source: Journal of Clinical Pharmacology. 2002 February; 42(2): 137-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831535&dopt=Abstract

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Oral symptoms at menopause--the role of hormone replacement therapy. Author(s): Tarkkila L, Linna M, Tiitinen A, Lindqvist C, Meurman JH. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 September; 92(3): 276-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552144&dopt=Abstract

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Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. Author(s): Leung W, Rose SR, Zhou Y, Hancock ML, Burstein S, Schriock EA, Lustig R, Danish RK, Evans WE, Hudson MM, Pui CH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 July 1; 20(13): 2959-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089225&dopt=Abstract

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Perspectives on the women's health initiative trial of hormone replacement therapy. Author(s): Brubaker K. Source: Obstetrics and Gynecology. 2003 April; 101(4): 813; Author Reply 813-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681893&dopt=Abstract

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Physician counseling on hormone replacement therapy and bone loss: do socioeconomic and racial characteristics of women influence counseling? Author(s): Neuner JM, McCarthy EP, Davis RB, Phillips RS. Source: Journal of Women's Health (2002). 2003 June; 12(5): 495-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869297&dopt=Abstract

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Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy. Author(s): Gambacciani M, Ciaponi M, Cappagli B, Monteleone P, Benussi C, Bevilacqua G, Genazzani AR. Source: Maturitas. 2003 July 25; 45(3): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818462&dopt=Abstract

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Postmenopausal hormone replacement therapy for the primary prevention of chronic conditions: recommendations and rationale. Author(s): Berg AO; U.S. Preventive Services Task Force. Source: The American Journal of Nursing. 2003 June; 103(6): 83-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802162&dopt=Abstract

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Postmenopausal hormone replacement therapy. Author(s): Grodstein F, Manson JE, Stampfer MJ. Source: Annals of Internal Medicine. 2003 April 15; 138(8): 688; Author Reply 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693903&dopt=Abstract

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Postmenopausal hormone replacement therapy. Author(s): Meyerson SJ. Source: Annals of Internal Medicine. 2003 April 15; 138(8): 687; Author Reply 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693902&dopt=Abstract

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Postmenopausal hormone replacement therapy. Author(s): Chausmer AB. Source: Annals of Internal Medicine. 2003 April 15; 138(8): 687-8; Author Reply 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693901&dopt=Abstract

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Prevalence of sexual dysfunction in a cohort of middle-aged women: influences of menopause and hormone replacement therapy. Author(s): Castelo-Branco C, Blumel JE, Araya H, Riquelme R, Castro G, Haya J, Gramegna G. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 July; 23(4): 426-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881088&dopt=Abstract

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Progesterone effects during sequential hormone replacement therapy. Author(s): Andreen L, Bixo M, Nyberg S, Sundstrom-Poromaa I, Backstrom T. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 May; 148(5): 571-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720542&dopt=Abstract

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Prospective association between hormone replacement therapy, heart rate, and heart rate variability. The Atherosclerosis risk in communities study. Author(s): Carnethon MR, Anthony MS, Cascio WE, Folsom AR, Rautaharju PM, Liao D, Evans GW, Heiss G. Source: Journal of Clinical Epidemiology. 2003 June; 56(6): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873652&dopt=Abstract

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Quality of life and costs associated with micronized progesterone and medroxyprogesterone acetate in hormone replacement therapy for nonhysterectomized, postmenopausal women. Author(s): Ryan N, Rosner A. Source: Clinical Therapeutics. 2001 July; 23(7): 1099-115. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519773&dopt=Abstract


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Quantification of ovarian stromal Doppler signals in postmenopausal women receiving hormone replacement therapy. Author(s): Pan HA, Li CH, Cheng YC, Wu MH, Chang FM. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851521&dopt=Abstract

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Questions and answers about hormone replacement therapy. Author(s): Acta Obstet Gynecol Scand. 2003 Jul;82(7):335-44 Source: Geriatric Nursing (New York, N.Y.). 2003 March-April; 24(2): 126-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12790856

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Randomized clinical trials of hormone replacement therapy for treatment or prevention of cardiovascular disease: a review of the findings. Author(s): Herrington DM, Klein KP. Source: Atherosclerosis. 2003 February; 166(2): 203-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535732&dopt=Abstract

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Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy. Author(s): Bork K, Fischer B, Dewald G. Source: The American Journal of Medicine. 2003 March; 114(4): 294-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681457&dopt=Abstract

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Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Author(s): Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Source: Cardiovascular Research. 2003 March; 57(3): 861-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618248&dopt=Abstract

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Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study. Author(s): Lokkegaard E, Pedersen AT, Heitmann BL, Jovanovic Z, Keiding N, Hundrup YA, Obel EB, Ottesen B. Source: Bmj (Clinical Research Ed.). 2003 February 22; 326(7386): 426. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595383&dopt=Abstract

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Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial. Author(s): Salmen T, Heikkinen AM, Mahonen A, Kroger H, Komulainen M, Pallonen H, Saarikoski S, Honkanen R, Maenpaa PH. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 February; 18(2): 319-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568409&dopt=Abstract

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Relation of aromatase gene polymorphism and hormone replacement therapy to serum estradiol levels, bone mineral density, and fracture risk in early postmenopausal women. Author(s): Salmen T, Heikkinen AM, Mahonen A, Kroger H, Komulainen M, Pallonen H, Saarikoski S, Honkanen R, Maenpaa PH. Source: Annals of Medicine. 2003; 35(4): 282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846271&dopt=Abstract

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Relationship between hormone replacement therapy, socioeconomic status, and coronary heart disease. Author(s): Grodstein F, Manson JE. Source: Jama : the Journal of the American Medical Association. 2003 January 1; 289(1): 44-5; Author Reply 45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503971&dopt=Abstract

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Reviews of hormone replacement therapy evidence support findings in recently halted trial. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2002 September 6; 13(17): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572547&dopt=Abstract

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Risks and benefits of hormone replacement therapy: the evidence speaks. Author(s): Humphries KH, Gill S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 April 15; 168(8): 1001-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695385&dopt=Abstract

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Risks and benefits of long-term hormone replacement therapy. Author(s): Biscup P. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 July 15; 60(14): 1419-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892026&dopt=Abstract


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Safety of hormone replacement therapy after mastectomy. Author(s): Hitchins RN. Source: The Medical Journal of Australia. 2002 June 17; 176(12): 617; Author Reply 61820. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064965&dopt=Abstract

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Safety of hormone replacement therapy after mastectomy. Author(s): Del Mar CB, Glasziou PP, Spinks AB, Sanders SL, Hilton DJ. Source: The Medical Journal of Australia. 2002 March 18; 176(6): 285. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999265&dopt=Abstract

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Selective modulation of postmenopausal women: cutting the Gordian knot of hormone replacement therapy with breast carcinoma. Author(s): Diamanti-Kandarakis E, Sykiotis GP, Papavassiliou AG. Source: Cancer. 2003 January 1; 97(1): 12-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491500&dopt=Abstract

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Serum leptin levels of menopausal women before and after hormone replacement therapy. Author(s): Li WL, Guo XY, Zhang JY, Peng P, Zhang YL. Source: Di Yi June Yi Da Xue Xue Bao. 2002 July; 22(7): 635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376297&dopt=Abstract

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Sexual dysfunction in middle-aged couples: an andrological approach in relation to hormone replacement therapy of the partners. Author(s): Di Bisceglie C, Tagliabue M, Vaccari P, Giangrande R, Brocato L, Manieri C. Source: J Endocrinol Invest. 2002; 25(10 Suppl): 91-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508933&dopt=Abstract

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Significant increase of benign endometrial cells on Papanicolaou smears in women using hormone replacement therapy. Author(s): Mount SL, Wegner EK, Eltabbakh GH, Olmstead JI, Drejet AE. Source: Obstetrics and Gynecology. 2002 September; 100(3): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220762&dopt=Abstract

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Smoking, estradiol metabolism and hormone replacement therapy. Author(s): Mueck AO, Seeger H. Source: Arzneimittel-Forschung. 2003; 53(1): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608008&dopt=Abstract

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Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. Author(s): Arjmandi BH, Khalil DA, Smith BJ, Lucas EA, Juma S, Payton ME, Wild RA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 104854. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629084&dopt=Abstract

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Study outlines further risks associated with hormone replacement therapy. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 September 5; 14(17): 1-2, 5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677336&dopt=Abstract

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Successful pregnancies after combined pentoxifylline-tocopherol treatment in women with premature ovarian failure who are resistant to hormone replacement therapy. Author(s): Letur-Konirsch H, Delanian S. Source: Fertility and Sterility. 2003 February; 79(2): 439-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568863&dopt=Abstract

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Taking hormone replacement therapy. Author(s): Griffiths F. Source: Bmj (Clinical Research Ed.). 2003 October 11; 327(7419): 820-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551063&dopt=Abstract

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Tear function tests and conjunctival impression cytology before and after hormone replacement therapy in postmenopausal women. Author(s): Pelit A, Bagis T, Kayaselcuk F, Dursun D, Akova Y, Aydin P. Source: Eur J Ophthalmol. 2003 May; 13(4): 337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872789&dopt=Abstract

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The changing view of hormone replacement therapy. Author(s): Vogel RA. Source: Reviews in Cardiovascular Medicine. 2003 Spring; 4(2): 68-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776015&dopt=Abstract

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The demise of HRT? The long-term safety of hormone replacement therapy. Author(s): Fenton A. Source: Expert Opinion on Drug Safety. 2003 July; 2(4): 341-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904091&dopt=Abstract


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The effect of decision aids on the agreement between women's and physicians' decisional conflict about hormone replacement therapy. Author(s): Legare F, O'Connor AM, Graham ID, Wells GA, Jacobsen MJ, Elmslie T, Drake ER. Source: Patient Education and Counseling. 2003 June; 50(2): 211-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781936&dopt=Abstract

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The effect of various regimens of hormone replacement therapy on mammographic breast density. Author(s): Christodoulakos GE, Lambrinoudaki IV, Panoulis KP, Vourtsi AD, Vlachos L, Georgiou E, Creatsas GC. Source: Maturitas. 2003 June 30; 45(2): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787969&dopt=Abstract

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The menopause and HRT. Hormone replacement therapy, cardiovascular and cerebrovascular disease. Author(s): Teede HJ. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 73-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763513&dopt=Abstract

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The short-term effects of different regimens of hormone replacement therapy on left ventricular structure and performance in healthy postmenopausal women. A prospective, controlled echocardiographic study. Author(s): Fenkci V, Yilmazer M, Alpaslan M, Onrat E, Fenkci S. Source: Gynecologic and Obstetric Investigation. 2003; 55(3): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865592&dopt=Abstract

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Trace elements and vitamin levels in menopausal women receiving hormone replacement therapy. Author(s): Meram I, Balat O, Tamer L, Ugur MG. Source: Clin Exp Obstet Gynecol. 2003; 30(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12731741&dopt=Abstract

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Two studies find lack of benefit from hormone replacement therapy. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 June 13; 14(11): 1-2, 5-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877113&dopt=Abstract

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Understanding attitudes of older women toward hormone replacement therapy. Author(s): Phelan EA, Buist DS, Anderson LA, Newton KM, Delaney KM, LaCroix AZ. Source: Preventive Medicine. 2001 January; 32(1): 49-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11162326&dopt=Abstract

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Understanding risk: women's perceived risk of menopause-related disease and the value they place on preventive hormone replacement therapy. Author(s): Ballard K. Source: Family Practice. 2002 December; 19(6): 591-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429660&dopt=Abstract

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Unscheduled bleeding during initiation of continuous combined hormone replacement therapy: a direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens. Author(s): Simon JA, Symons JP; femhrt Study Investigators. Source: Menopause (New York, N.Y.). 2001 September-October; 8(5): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528357&dopt=Abstract

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Update: the latest on hormone replacement therapy. Author(s): Packin GS. Source: J Am Osteopath Assoc. 2000 October; 100(10 Su Pt 1): S2-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105456&dopt=Abstract

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Use of combination hormone replacement therapy in light of recent data from the Women's Health Initiative. Author(s): Kaunitz AM; Women's Health Initiative. Source: Medscape Women's Health [electronic Resource]. 2002 July-August; 7(4): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466740&dopt=Abstract

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Use of hormone replacement therapy among Chilean women: a comparison between socioeconomic levels. Author(s): Blumel JE, Castelo-Branco C, Riquelme R, Araya H, Jaramillo P, Tacla X, Colodron M, Lavin P. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 377-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218727&dopt=Abstract

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Use of hormone replacement therapy among Danish nurses at increased risk of osteoporosis. Author(s): Hundrup YA, Thoning H, Rasmussen NK, Obel EB, Philip J. Source: International Journal of Behavioral Medicine. 2003; 10(3): 269-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14525721&dopt=Abstract


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Use of hormone replacement therapy by menopausal women in six family-practice teaching clinics in Israel. Author(s): Vinker S, Kaplan B, Yaphe J, Cohen O, Shumla V, Shapira G, Shofty I, Kitai E. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725667&dopt=Abstract

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Use of hormone replacement therapy: women's representations of menopause and beauty care practices. Author(s): Fauconnier A, Ringa V, Delanoe D, Falissard B, Breart G. Source: Maturitas. 2000 June 30; 35(3): 215-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936738&dopt=Abstract

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Use of multiple providers for regular care and women's receipt of hormone replacement therapy counseling. Author(s): Gallagher TC, Geling O, Comite F. Source: Medical Care. 2001 October; 39(10): 1086-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11567171&dopt=Abstract

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Vaginal bleeding patterns in women receiving hormone replacement therapy. Impact of various progestogen regimens. Author(s): Thorneycroft IH, Gibbons WE. Source: J Reprod Med. 1999 February; 44(2 Suppl): 209-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392034&dopt=Abstract

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Vaginal micronized progesterone in continuous hormone replacement therapy. A prospective randomized study. Author(s): Ferrero S, Gerbaldo D, Fulcheri E, Cristoforoni P. Source: Minerva Ginecol. 2002 December; 54(6): 519-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432337&dopt=Abstract

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Vaginal ring delivery of hormone replacement therapy--a review. Author(s): Dezarnaulds G, Fraser IS. Source: Expert Opinion on Pharmacotherapy. 2003 February; 4(2): 201-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562310&dopt=Abstract

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Vaginal rings delivering progesterone and estradiol may be a new method of hormone replacement therapy. Author(s): Maruo T, Mishell DR, Ben-Chetrit A, Hochner-Celnikier D, Hamada AL, Nash HA. Source: Fertility and Sterility. 2002 November; 78(5): 1010-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413986&dopt=Abstract

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Variation in the efficacy of hormone replacement therapy in the prevention of hip fracture. Swedish Hip Fracture Study Group. Author(s): Michaelsson K, Baron JA, Johnell O, Persson I, Ljunghall S. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1998; 8(6): 540-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326058&dopt=Abstract

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Vascular function of forearm microcirculation in postmenopausal women with type 2 diabetes: potential benefit of hormone replacement therapy? Author(s): Ching HL, Watts GF, Dhaliwal SS, Barrett PH, Stuckey BG. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725662&dopt=Abstract

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Vasomotor and vascular effects of hormone replacement therapy. Author(s): Ganz P. Source: The American Journal of Cardiology. 2002 July 3; 90(1A): 11F-16F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106634&dopt=Abstract

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Vertebral bone mineral density, content and area in 8789 normal women aged 33-73 years who have never had hormone replacement therapy. Author(s): Shipman AJ, Guy GW, Smith I, Ostlere S, Greer W, Smith 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. 1999; 9(5): 420-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10550461&dopt=Abstract

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Vertebral morphometry: repeat scan precision using the Lunar Expert-XL and the Hologic 4500A. A study for the 'WISDOM' RCT of hormone replacement therapy. Author(s): Crabtree N, Wright J, Walgrove A, Rea J, Hanratty L, Lunt M, Fogelman I, Palmer R, Vickers M, Compston JE, Reev J. 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(6): 537-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982171&dopt=Abstract

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Visual function in menopause: the role of hormone replacement therapy. Author(s): Guaschino S, Grimaldi E, Sartore A, Mugittu R, Mangino F, Bortoli P, Pensiero S, Vinciguerra A, Perissutti P. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544677&dopt=Abstract


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What are the key issues women face when ending hormone replacement therapy? Author(s): Utian WH. Source: Cleve Clin J Med. 2003 February; 70(2): 93-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636339&dopt=Abstract

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What factors are associated with a woman's decision to take hormone replacement therapy? Evaluated in the context of a decision aid. Author(s): Clark HD, O'Connor AM, Graham ID, Wells GA. Source: Health Expectations : an International Journal of Public Participation in Health Care and Health Policy. 2003 June; 6(2): 110-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752739&dopt=Abstract

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What is the available evidence for hormone replacement therapy in women with stress urinary incontinence? Author(s): Al-Badr A, Ross S, Soroka D, Drutz HP. Source: J Obstet Gynaecol Can. 2003 July; 25(7): 567-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851668&dopt=Abstract

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What is the cardioprotective role of hormone replacement therapy? Author(s): Hodis HN, Mack WJ, Lobo R. Source: Current Atherosclerosis Reports. 2003 January; 5(1): 56-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562544&dopt=Abstract

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What is this thing called hormone replacement therapy? Discursive construction of medication in situated practice. Author(s): Stephens C, Budge RC, Carryer J. Source: Qualitative Health Research. 2002 March; 12(3): 347-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918100&dopt=Abstract

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What your doctor is reading. Hormone replacement therapy. Author(s): Roberts SS. Source: Diabetes Self Manag. 2002 November-December; 19(6): 78-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561772&dopt=Abstract

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WHI findings another blow to hormone replacement therapy. Author(s): Traynor K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 July 15; 60(14): 1409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892024&dopt=Abstract

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Women & diabetes. Menopause. The latest on hormone replacement therapy. Author(s): Ross HL. Source: Diabetes Self Manag. 2002 July-August; 19(4): 90, 92, 95-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533854&dopt=Abstract

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CHAPTER 2. NUTRITION AND HORMONE REPLACEMENT THERAPY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hormone replacement therapy.

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

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


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

A cohort study of hormone replacement therapy given to women previously treated for breast cancer. Author(s): Women's Health Institute, Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia. Source: Dew, J Eden, J Beller, E Magarey, C Schwartz, P Crea, P Wren, B Climacteric. 1998 June; 1(2): 137-42 1369-7137

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A comparison of tibolone and hormone replacement therapy on coronary artery and myocardial function in ovariectomized atherosclerotic monkeys. Author(s): The Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA. [email protected] Source: Williams, J Koudy Hall, Jason Anthony, Mary S Register, Thomas C Reis, Steven E Clarkson, Thomas B Menopause. 2002 Jan-February; 9(1): 41-51 1072-3714

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A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. Author(s): Papworth Hospital, Cambridge, UK. Source: Clarke, S C Kelleher, J Lloyd Jones, H Slack, M Schofiel, P M BJOG. 2002 September; 109(9): 1056-62 1470-0328

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Allopathic and complementary alternatives to hormone replacement therapy. Author(s): Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Source: Eichholz, A C Mahavni, V Sood, A K Expert-Opin-Pharmacother. 2002 July; 3(7): 949-55 1465-6566

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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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Bioidentical hormone replacement therapy. A natural option for perimenopause and beyond. Source: Walker, C R Adv-Nurse-Pract. 2001 May; 9(5): 39-42, 45 1096-6293

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Changes in coagulation factors and fibrinolytic components of postmenopausal women receiving continuous hormone replacement therapy. Author(s): Department of Gynecology and Obstetrics, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Source: Nozaki, M Ogata, R Koera, K Hashimoto, K Nakano, H Climacteric. 1999 June; 2(2): 124-30 1369-7137

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Circadian rhythm of melatonin in postmenopausal asthmatic women with hormone replacement therapy. Author(s): Department of Pathophysiology and Endocrinology, Silesian Medical University, Zabrze, Poland. [email protected] Source: Kos Kudla, B Ostrowska, Z Marek, B Kajdaniuk, D Ciesielska Kopacz, N Kudla, M Mazur, B Glogowska Szelag, J Nasiek, M Neuroendocrinol-Lett. 2002 June; 23(3): 2438 0172-780X

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Comparison of different treatment modalities for postmenopausal patients with osteopenia: hormone replacement therapy, calcitonin and clodronate. Author(s): Department of Obstetrics and Gynecology, Gazi University School of Medicine, Besevler, Ankara, Turkey. Source: Tiras, M B Noyan, V Yildiz, A Biberoglu, K Climacteric. 2000 June; 3(2): 92-101 1369-7137

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Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hormone replacement therapy in postmenopausal women. Author(s): Clinical Research Department, Jenapharm GmbH & Co. KG, Otto-Schott-S. 15, D-07745 Jena, Germany. Source: Graser, T Koytchev, R Muller, A Oettel, M Climacteric. 2000 June; 3(2): 109-18 1369-7137

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Controversial issues in climacteric medicine I. Cardiovascular disease and hormone replacement therapy. International Menopause Society Expert Workshop. 13-16 October 2000, royal society of medicine, London, UK. Author(s): Department of Gynecology and Obstetrics, University of Pisa, Via Roma 35, 56126 Pisa, Italy. Source: Genazzani, A R Gambacciani, M Climacteric. 2000 December; 3(4): 233-40 13697137

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Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. Author(s): Eli Lilly and Company, Bad Homburg, Germany. Source: Nickelsen, T Creatsas, G Rechberger, T Depypere, H Erenus, M Quail, D Arndt, T Bonnar, J Climacteric. 2001 December; 4(4): 320-31 1369-7137

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Effect of hormone replacement therapy on self-reported cognitive symptoms: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. Author(s): Wake Forest University School of Medicine, Department of Public Health Sciences, Winston-Salem, NC 27157, USA. Source: Reboussin, B A Greendale, G A Espeland, M A Climacteric. 1998 September; 1(3): 172-9 1369-7137

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Effects of hormone replacement therapy on olfactory sensitivity: cross-sectional and longitudinal studies. Author(s): Center for Alzheimer Disease and Related Disorders, Department of Surgery, Division of Otolaryngology, Neurology, Southern Illinois University School of Medicine, PO Box 19643, Springfield, Illinois 62794-9643, USA. Source: Hughes, L F McAsey, M E Donathan, C L Smith, T Coney, P Struble, R G Climacteric. 2002 June; 5(2): 140-50 1369-7137

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Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal women. Author(s): Menox Institute, Vienna, Austria. Source: Huber, J Palacios, S Berglund, L Hanggi, W Sathanandan, S M Christau, S Helmond, F BJOG. 2002 August; 109(8): 886-93 1470-0328

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Electrocardiogram pattern in hypercholesterolemic women: the influence of hormone replacement therapy. Author(s): Department of Obstetrics and Gynecology, Lund University Hospital, Lund, Sweden.


Source: Akerblom, M Li, C Samsioe, G Climacteric. 1998 December; 1(4): 258-63 13697137 •

Factors associated with endometrial bleeding in continuous hormone replacement therapy. Author(s): Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Source: Shau, Wen Yi Hsieh, Ching Chang Hsieh, T'sang T'ang Hung, Tai Ho Huang, Kuo En Menopause. 2002 May-June; 9(3): 188-94 1072-3714

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva, Israel. [email protected] Source: Kaplan, B Aschkenazi Steinberg, S Yogev, Y Nahum, R Sulkes, J Phisher, M Menopause. 2002 Sep-October; 9(5): 354-9 1072-3714

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Hormone replacement therapy (HRT) and ischaemic heart disease: getting to the heart of the matter. Author(s): Department of Obstetrics & Gynaecology, National University Hospital, Singapore. [email protected] Source: Chew, S Ng, S C Singapore-Med-J. 2002 January; 43(1): 041-4 0037-5675

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Hyperhomocysteinaemia and cardiovascular risk in female ovariectomized rats: role of folic acid and hormone replacement therapy. Author(s): Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Egypt. [email protected] Source: el Swefy, Sahar E Ali, Sousou I Asker, Mervat E Mohamed, Hoda E J-PharmPharmacol. 2002 March; 54(3): 391-7 0022-3573

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Intrauterine application of progestins in hormone replacement therapy: a review. Source: Riphagen, F E Climacteric. 2000 September; 3(3): 199-211 1369-7137

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Lifestyle factors and choice of hormone replacement therapy among Danish nurses. Author(s): National Institute of Public Health, Copenhagen, Denmark. [email protected] Source: Hundrup, Yrsa A Thoning, Henrik Obel, Erik B Rasmussen, Niels K Philip, John Scand-J-Public-Health. 2002; 30(1): 47-53 1403-4948

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Low-dose hormone replacement therapy: effects on bone. Author(s): Department of Obstetrics and Gynecology Piero Fioretti, University of Pisa, Via Roma 67, 56100 Pisa, Italy. Source: Gambacciani, M Monteleone, P Genazzani, A R Climacteric. 2002 June; 5(2): 1359 1369-7137

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Medical issues and hormone replacement therapy. Author(s): Washington Hospital Center, Geriatrics and Long Term Care, Room 2B-39, 110 Irving Street, NW, Washington, DC 20010, USA. [email protected] Source: Harris, P F Curr-Womens-Health-Repage 2002 October; 2(5): 373-81 1534-5874

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Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Source: Wells, G Tugwell, P Shea, B Guyatt, G Peterson, J Zytaruk, N Robinson, V Henry, D O'Connell, D Cranney, A Endocr-Revolume 2002 August; 23(4): 529-39 0163769X

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Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. An open-label pilot efficacy and safety study. Author(s): Department of Internal Med. IV, Klinikum Leverkusen, Teaching Hospital of the University of Cologne, Germany. [email protected] Source: Ringe, J D Setnikar, I Rheumatol-Int. 2002 May; 22(1): 27-32 0172-8172

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Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. Author(s): After Completion of Therapy Program and the Department of HematologyOncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. [email protected] Source: Leung, Wing Rose, Susan R Zhou, Yinmei Hancock, Michael L Burstein, Stephen Schriock, Elizabeth A Lustig, Robert Danish, Robert K Evans, William E Hudson, Melissa M Pui, Ching Hon J-Clin-Oncol. 2002 July 1; 20(13): 2959-64 0732-183X

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Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic. Author(s): Chelsea and Westminster Hospital, London, UK. Source: Vashisht, A Domoney, C L Cronje, W Studd, J W Climacteric. 2001 September; 4(3): 250-6 1369-7137

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Serum leptin levels of menopausal women before and after hormone replacement therapy. Author(s): Department of Gynecology and Obstetrics, General Hospital of Guangzhou Command, Guangzhou 510010, China. Source: Li, W L Guo, X Y Zhang, J Y Peng, P Zhang, Y L Di-Yi-Jun-Yi-Da-Xue-Xue-Bao. 2002 July; 22(7): 635-6 1000-2588

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Sex hormone replacement therapy reverses altered venous contractility in rats after pharmacological ovariectomy. Author(s): Second Department of Obstetrics and Gynecology, Semmelweis University, Faculty of Medicine, Budapest, Hungary. Source: Varbiro, Szabolcs Vajo, Zoltan Nadasy, Gyorgy L Monos, Emil Acs, Nandor Lorant, Miklos Felicetta, James V Sze, Bela Menopause. 2002 Mar-April; 9(2): 122-6 10723714

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Tamoxifen, hormone receptors and hormone replacement therapy in women previously treated for breast cancer: a cohort study. Author(s): School of Women's and Children's Health, University of New South Wales, Royal Hospital for Women, Randwick, Australia. Source: Dew, J E Wren, B G Eden, J A Climacteric. 2002 June; 5(2): 151-5 1369-7137

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The association of hormone replacement therapy and coronary calcium as determined by electron beam tomography. Author(s): Departments of Imaging (Division of Nuclear Medicine), Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Source: Schisterman, E F Gallagher, A M Bairey Merz, C N Whitcomb, B W Faraggi, D Moysich, K B Lewin, H J-Womens-Health-Gend-Based-Med. 2002 September; 11(7): 6318 1524-6094

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The effect of hormone replacement therapy on appendicular lean tissue mass in early postmenopausal women. Author(s): Center for Clinical and Basic Research, Ballerup, Denmark. [email protected] Source: Tanko, Laszlo B Movsesyan, Lusine Svendsen, Ole L Christiansen, Claus Menopause. 2002 Mar-April; 9(2): 117-21 1072-3714


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The effects of growth hormone replacement therapy on bone metabolism in adultonset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. Author(s): Department of Endocrinology, University Hospital Gasthuisberg, Leuven, Belgium. Source: Bex, M Abs, R Maiter, D Beckers, A Lamberigts, G Bouillon, R J-Bone-Miner-Res. 2002 June; 17(6): 1081-94 0884-0431

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Which is the appropriate hormone replacement therapy after sub-total hysterectomy? Author(s): Department of Obstetrics and Gynaecology, Farnborough Hospital, Kent, UK. Source: Imoh Ita, F Morgan, P Rymer, J Climacteric. 2000 March; 3(1): 65-7 1369-7137

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

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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

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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/

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

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

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The following is a specific Web list relating to hormone replacement therapy; 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 D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Alternative names: Calciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Alternative names: Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com

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Minerals Alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com


Magnesium Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Integrative Medicine Communications; www.drkoop.com •

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

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

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “hormone replacement therapy” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •

Informed Choices: Your Most Valuable Role in Menopause Care is Education Source: Advance for Nurse Practitioners. 10(1): 65-68. January 2002. Summary: This article provides information for nurse practitioners on menopause and how to treat its symptoms. It lists recommendations from the North American Menopause Society about how to help women achieve optimum health through the menopause transition, and discusses the pharmacologic treatment of menopause and post menopause. Alternative treatments for women who are reluctant or unable to take hormone replacement therapy are also covered. The article includes tables of the most common menopausal symptoms and the most commonly used hormone replacement therapies. 11 references.


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Alternative Therapies for Managing Menopausal Symptoms Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2002. 3 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D169. Summary: This consumer advisory alerts consumers about recent research demonstrating that long-term use of estrogen in combination with progestin results in more risks than benefits. It discusses the use of alternative therapies for managing menopausal symptoms, provides information on the current scientific evidence of the effectiveness and safety of these therapies, and offers advice to consumers about using hormone replacement therapy and alternative therapies for menopausal symptoms. The advisory also provides a list of sources for further information.

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 hormone replacement therapy 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 “hormone replacement therapy” (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 hormone replacement therapy: •

“Natural” hormone replacement therapy and dietary supplements used in the treatment of menopausal symptoms. Author(s): Taffe AM, Cauffield J. Source: Lippincott's Primary Care Practice. 1998 May-June; 2(3): 292-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9644444&dopt=Abstract

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A novel concept to preserve the beneficial effects of hormone replacement therapy in bilaterally female ovariectomized rats: role of lovastatin therapy. Author(s): El-Swefy SE, Asker ME, Ali SI, Mohammed HE. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2002 March; 45(3): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11884211&dopt=Abstract

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A nurse's guide to hormone replacement therapy. Author(s): Moore AA, Noonan MD. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 1999; 28(6 Suppl 1): 13-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608492&dopt=Abstract

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A nurse's guide to hormone replacement therapy. Author(s): Moore AA, Noonan MD. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 1996 January; 25(1): 24-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8627399&dopt=Abstract

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A pilot study comparing the clinical effects of Jia-Wey Shiau-Yau San, a traditional Chinese herbal prescription, and a continuous combined hormone replacement therapy in postmenopausal women with climacteric symptoms. Author(s): Chen LC, Tsao YT, Yen KY, Chen YF, Chou MH, Lin MF. Source: Maturitas. 2003 January 30; 44(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568736&dopt=Abstract

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A practical guide to prescribing hormone replacement therapy. Author(s): McKinney KA, Thompson W. Source: Drugs. 1998 July; 56(1): 49-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9664198&dopt=Abstract

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Additive effect of alfacalcidol on bone mineral density of the lumbar spine in Taiwanese postmenopausal women treated with hormone replacement therapy and calcium supplementation: a randomized 2-year study. Author(s): Chen M, Chow SN. Source: Clinical Endocrinology. 2001 August; 55(2): 253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531934&dopt=Abstract

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Allopathic and complementary alternatives to hormone replacement therapy. Author(s): Eichholz AC, Mahavni V, Sood AK. Source: Expert Opinion on Pharmacotherapy. 2002 July; 3(7): 949-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083994&dopt=Abstract

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Alternatives to conventional hormone replacement therapy. Author(s): Taylor M. Source: Compr Ther. 1997 August; 23(8): 514-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283741&dopt=Abstract

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Alternatives to hormone replacement therapy. Do they measure up to estrogen? Author(s): Cornell S. Source: Adv Nurse Pract. 1997 July; 5(7): 45-6, 49, 72. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459944&dopt=Abstract

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Ascorbic acid status in postmenopausal women with hormone replacement therapy. Author(s): Kuo SM, Stout A, Wactawski-Wende J, Leppert PC.


Source: Maturitas. 2002 January 30; 41(1): 45-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809342&dopt=Abstract •

Bioidentical hormone replacement therapy. A natural option for perimenopause and beyond. Author(s): Walker CR. Source: Adv Nurse Pract. 2001 May; 9(5): 39-42, 45. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400258&dopt=Abstract

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Bioidentical hormone replacement therapy. Customizing care for perimenopausal and menopausal women. Author(s): Romero M. Source: Adv Nurse Pract. 2002 November; 10(11): 47-8, 51-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478948&dopt=Abstract

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Bone effects of transdermal hormone replacement therapy in postmenopausal women as evaluated by means of ultrasound: an open one-year prospective study. Author(s): de Aloysio D, Rovati LC, Cadossi R, Paltrinieri F, Mauloni M, Mura M, Penacchioni P, Ventura V. Source: Maturitas. 1997 May; 27(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9158079&dopt=Abstract

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By the way, Doctor. I've seen advertisements for red clover as a treatment for menopausal symptoms. Is it an effective alternative to hormone replacement therapy (HRT)? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 December; 9(5): 7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751101&dopt=Abstract

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Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss. Author(s): Aloia JF, Vaswani A, Yeh JK, Ross PL, Flaster E, Dilmanian FA. Source: Annals of Internal Medicine. 1994 January 15; 120(2): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8256988&dopt=Abstract

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Carcinoma of the breast and hormone replacement therapy for osteoporosis. Author(s): Crawshaw A. Source: Int J Clin Pract. 2000 March; 54(2): 99-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10824364&dopt=Abstract


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Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. Author(s): Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 259-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711012&dopt=Abstract

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Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Author(s): Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan AS, Haines CJ, Chan TY, Li M, Sham A. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 352-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851519&dopt=Abstract

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Cutting through the hype. Hormone replacement therapy with DHEA. Author(s): Ricchini W. Source: Adv Nurse Pract. 1998 November; 6(11): 73-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9919066&dopt=Abstract

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Disputes definition of 'hormone replacement therapy'. Author(s): Wright JV. Source: Alternative Therapies in Health and Medicine. 1996 July; 2(4): 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8795910&dopt=Abstract

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Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, doubleblind trial. Author(s): Stark KD, Park EJ, Maines VA, Holub BJ. Source: The American Journal of Clinical Nutrition. 2000 August; 72(2): 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10919932&dopt=Abstract

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Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. Author(s): Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes M, Gordon DJ, Proschan M, Younes N, Verter JI. Source: Jama : the Journal of the American Medical Association. 2002 November 20; 288(19): 2432-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435256&dopt=Abstract

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Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause. Author(s): Sarrel PM.


Source: Journal of Women's Health & Gender-Based Medicine. 2000; 9 Suppl 1: S25-32. Review. Erratum In: J Womens Health Gend Based Med 2001 January-February; 10(1): 91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695871&dopt=Abstract •

Estrogenic activity of two standardized red clover extracts (Menoflavon) intended for large scale use in hormone replacement therapy. Author(s): Dornstauder E, Jisa E, Unterrieder I, Krenn L, Kubelka W, Jungbauer A. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 July; 78(1): 6775. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530286&dopt=Abstract

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Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety. Author(s): De Leo V, la Marca A, Morgante G, Lanzetta D, Florio P, Petraglia F. Source: Maturitas. 2001 August 25; 39(2): 185-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514117&dopt=Abstract

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Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Author(s): Lemay A, Dodin S, Kadri N, Jacques H, Forest JC. Source: Obstetrics and Gynecology. 2002 September; 100(3): 495-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220769&dopt=Abstract

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Genistein appears to prevent early postmenopausal bone loss as effectively as hormone replacement therapy. Author(s): Cotter A, Cashman KD. Source: Nutrition Reviews. 2003 October; 61(10): 346-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604267&dopt=Abstract

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 354-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218724&dopt=Abstract

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Hormone replacement therapy and coronary artery disease: buried alive? Author(s): Bahl VK, Naik N. Source: Indian Heart J. 2002 January-February; 54(1): 23-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999084&dopt=Abstract

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Hormone replacement therapy in women with a history of breast cancer. Author(s): Ylikorkala O, Metsa-Heikkila M.


Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 December; 16(6): 469-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626034&dopt=Abstract •

Hormone replacement therapy trials: an update. Author(s): Duvernoy CS, Mosca L. Source: Current Atherosclerosis Reports. 2002 March; 4(2): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822980&dopt=Abstract

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Hormone replacement therapy: all a woman could desire? Author(s): Adams S. Source: J Fam Health Care. 2002; 12(4): 105-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416018&dopt=Abstract

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Hormone replacement therapy: current controversies. Author(s): Davison S, Davis SR. Source: Clinical Endocrinology. 2003 March; 58(3): 249-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608928&dopt=Abstract

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Hormone replacement therapy: I. A pharmacoeconomic appraisal of its therapeutic use in menopausal symptoms and urogenital estrogen deficiency. Author(s): Whittington R, Faulds D. Source: Pharmacoeconomics. 1994 May; 5(5): 419-45. Review. Erratum In: Pharmacoeconomics 1995 September; 8(3): 244. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10147233&dopt=Abstract

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Hormone replacement therapy: separating fact from fallacy. Author(s): Shepherd JE. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2002 January-February; 42(1): 122-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833505&dopt=Abstract

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Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. Author(s): Heikkinen AM, Tuppurainen MT, Niskanen L, Komulainen M, Penttila I, Saarikoski S. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1997 November; 137(5): 495-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9405029&dopt=Abstract

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Management of surgically hypogonadal patients unable to take sex hormone replacement therapy. Author(s): Nieman LK.


Source: Endocrinology and Metabolism Clinics of North America. 2003 June; 32(2): 32536. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800534&dopt=Abstract •

Managing the menopause: phyto-oestrogens or hormone replacement therapy? Author(s): Eden JA. Source: Annals of Medicine. 2001 February; 33(1): 4-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310938&dopt=Abstract

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Menopause and hormone replacement therapy from holistic and medical perspectives. Author(s): Herrick CA, Douglas V, Carlson JH. Source: Issues in Mental Health Nursing. 1996 March-April; 17(2): 153-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8707535&dopt=Abstract

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Menopause and hormone replacement therapy: an overview. Author(s): Hammond CB. Source: Obstetrics and Gynecology. 1996 February; 87(2 Suppl): 2S-15S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8559549&dopt=Abstract

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Menopause, naturally. Exploring alternatives to traditional hormone replacement therapy. Author(s): Lindsay SH. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 1999 October-November; 3(5): 32-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10827581&dopt=Abstract

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More on oral contraceptives, drug interactions, herbal medicines, and hormone replacement therapy. Author(s): Shader RI, Greenblatt DJ. Source: Journal of Clinical Psychopharmacology. 2000 August; 20(4): 397-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917398&dopt=Abstract

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Myocardial blood flow and flow reserve in response to short-term cyclical hormone replacement therapy in postmenopausal women. Author(s): Duvernoy CS, Rattenhuber J, Seifert-Klauss V, Bengel F, Meyer C, Schwaiger M. Source: J Gend Specif Med. 2001; 4(3): 21-7, 47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605352&dopt=Abstract

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Perimenopausal and postmenopausal hormone replacement therapy. Part 1. An update of the literature on benefits and risks. Author(s): Lichtman R.


Source: Journal of Nurse-Midwifery. 1996 January-February; 41(1): 3-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8820754&dopt=Abstract •

Perimenopausal and postmenopausal hormone replacement therapy. Part 2. Hormonal regimens and complementary and alternative therapies. Author(s): Lichtman R. Source: Journal of Nurse-Midwifery. 1996 May-June; 41(3): 195-210. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8708803&dopt=Abstract

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Phytoestrogens as hormone replacement therapy: an evidence-based approach. Author(s): Carusi D. Source: Prim. Care Update Ob Gyns. 2000 November 1; 7(6): 253-259. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11077239&dopt=Abstract

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Phytoestrogens for hormone replacement therapy? Author(s): Wuttke W, Jarry H, Westphalen S, Christoffel V, Seidlova-Wuttke D. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 133-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650710&dopt=Abstract

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Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy? Author(s): Wuttke W, Jarry H, Becker T, Schultens A, Christoffel V, Gorkow C, SeidlovaWuttke D. Source: Maturitas. 2003 March 14; 44 Suppl 1: S9-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609555&dopt=Abstract

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Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Author(s): U.S. Preventive Services Task Force. Source: Annals of Internal Medicine. 2002 November 19; 137(10): 834-9. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435221&dopt=Abstract

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Prescribing hormone replacement therapy for menopausal symptoms. Author(s): McNagny SE. Source: Annals of Internal Medicine. 1999 October 19; 131(8): 605-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523222&dopt=Abstract

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Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic. Author(s): Vashisht A, Domoney CL, Cronje W, Studd JW.


Source: Climacteric : the Journal of the International Menopause Society. 2001 September; 4(3): 250-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588949&dopt=Abstract •

Soy phytoestrogens: an adjunct to hormone replacement therapy? Author(s): Birge SJ. Source: Menopause (New York, N.Y.). 2000 July-August; 7(4): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914612&dopt=Abstract

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Soy phytoestrogens: what will be their role in postmenopausal hormone replacement therapy? Author(s): Clarkson TB. Source: Menopause (New York, N.Y.). 2000 March-April; 7(2): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10746888&dopt=Abstract

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Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. Author(s): Arjmandi BH, Khalil DA, Smith BJ, Lucas EA, Juma S, Payton ME, Wild RA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 104854. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629084&dopt=Abstract

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Soybean isoflavones as an alternative to traditional hormone replacement therapy: are we there yet? Author(s): Burke GL, Vitolins MZ, Bland D. Source: The Journal of Nutrition. 2000 March; 130(3): 664S-5S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10702606&dopt=Abstract

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Soyfoods and soybean phyto-oestrogens (isoflavones) as possible alternatives to hormone replacement therapy (HRT). Author(s): Messina M. Source: European Journal of Cancer (Oxford, England : 1990). 2000 September; 36 Suppl 4: S71-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056326&dopt=Abstract

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Supplemental and complementary alternatives to hormone replacement therapy. Author(s): Keller C, Fullerton J, Mobley C. Source: Journal of the American Academy of Nurse Practitioners. 1999 May; 11(5): 18798. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10504933&dopt=Abstract


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The potential of soybean phytoestrogens for postmenopausal hormone replacement therapy. Author(s): Clarkson TB, Anthony MS, Williams JK, Honore EK, Cline JM. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1998 March; 217(3): 365-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9492349&dopt=Abstract

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Therapeutic options: hormone replacement therapy-soy therapy. Author(s): Merritt JC. Source: Journal of the National Medical Association. 2001 July-August; 93(7-8): 288-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491281&dopt=Abstract

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Treating hot flushes without hormone replacement therapy. Author(s): Seibel MM. Source: The Journal of Family Practice. 2003 April; 52(4): 291-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681090&dopt=Abstract

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Women's beliefs about “natural” hormones and natural hormone replacement therapy. Author(s): Adams C, Cannell S. Source: Menopause (New York, N.Y.). 2001 November-December; 8(6): 433-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723417&dopt=Abstract

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

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

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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 hormone replacement therapy; 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 Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Erectile Dysfunction Source: Healthnotes, Inc.; www.healthnotes.com Fibrocystic Breast Disease Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypothyroidism Source: Integrative Medicine Communications; www.drkoop.com


Menopause Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com Urinary Incontinence Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Black Cohosh Alternative names: Cimicifuga racemosa Source: Healthnotes, Inc.; www.healthnotes.com Black Cohosh Alternative names: Cimicifuga racemosa (actea), Black Snakeroot Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Black Snakeroot Source: Integrative Medicine Communications; www.drkoop.com Calciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html


Cholecalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Cimicifuga Racemosa (ACTEA) Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Estradiol Source: Healthnotes, Inc.; www.healthnotes.com Estrogens (Combined) Source: Healthnotes, Inc.; www.healthnotes.com Forskolin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10025,00.html Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Natural Progesterone Cream Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10099,00.html Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Red Clover Source: Integrative Medicine Communications; www.drkoop.com Wild Yam Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10070,00.html

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.

139

CHAPTER 4. DISSERTATIONS REPLACEMENT THERAPY

ON

HORMONE

Overview In this chapter, we will give you a bibliography on recent dissertations relating to hormone replacement therapy. 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 “hormone replacement therapy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hormone replacement therapy, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Hormone Replacement Therapy 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 hormone replacement therapy. 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: •

Are Perimenopausal and Postmenopausal Women More Apt to Choose Hormone Replacement Therapy If They Are More Knowledgeable about the Effects of Said Therapy? by Pineda, Cleo C.; MS from California State University, Long Beach, 2002, 58 pages http://wwwlib.umi.com/dissertations/fullcit/1410331

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Coverage of Hormone Replacement Therapy in Popular Periodicals and Professional Journals by Badie, Homa Baher, PhD from Texas Woman's University, 1997, 125 pages http://wwwlib.umi.com/dissertations/fullcit/9804893

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Effect of Web-based Computer-tailoring on Women's Intention to Continue or Begin to Use Hormone Replacement Therapy to Lower Their Risk for Osteoporosis by McGinley, Anne Marie; PhD from University of Pennsylvania, 2002, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3043913


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Effects of Hormone Replacement Therapy on Insulin Resistance in Cynomolgus Monkeys by Shadoan, Melanie Kimbrell; PhD from Wake Forest University, 2002, 134 pages http://wwwlib.umi.com/dissertations/fullcit/3082973

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Effects of N-3 Supplementation in Postmenopausal Women Receiving and Not Receiving Hormone Replacement Therapy by Stark, Kenneth Douglas; PhD from University of Guelph (canada), 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67237

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Enhancing Women's Decision-making Concerning the Use of Hormone Replacement Therapy by Katra, Jane Elizabeth, PhD from University of Oregon, 1993, 211 pages http://wwwlib.umi.com/dissertations/fullcit/9405189

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Exploratory Research of the Factors That Influence a Woman's Decision Regarding Hormone Replacement Therapy by Prue, Christine Ellen, PhD from University of Maryland College Park, 1998, 183 pages http://wwwlib.umi.com/dissertations/fullcit/9836466

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Factors Associated with the Utilization of Hormone Replacement Therapy among Postmenopausal Women: a Case Study of a Suburban Philadelphia Retirement Community (Pennsylvania) by Powers, Barbara L., PhD from Temple University, 1996, 94 pages http://wwwlib.umi.com/dissertations/fullcit/9623796

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Factors That Influence a Woman's Decision to Initiate or Decline the Use of Hormone Replacement Therapy by Arruda, Judy Ann; MS from University of Nevada, Reno, 2002, 47 pages http://wwwlib.umi.com/dissertations/fullcit/1410208

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Hormone Replacement Therapy: Health State Preference Measurement and Markov Model Based Decision-Making Regarding Its Use by Datta, Santanu Kumar; PhD from The University of North Carolina at Chapel Hill, 2002, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3070838

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Menopausal Women Receiving and Not Receiving Hormone Replacement Therapy: Generalized Contentment, Marital Satisfaction, Sexual Satisfaction, Health Locus of Control, and Sex Role Identity Self-reports by St. Hillier, Donna Jones, PhD from The Florida State University, 1989, 178 pages http://wwwlib.umi.com/dissertations/fullcit/8916205

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Physical Activity, Hormone Replacement Therapy, and Atherosclerotic Risk in Midlife Women by Hunter, Carol J.; PhD from The University of New Mexico, 1999, 157 pages http://wwwlib.umi.com/dissertations/fullcit/9938979

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Physical Activity, Hormone Replacement Therapy, and Insulin-resistant Coronary Artery Disease Risk Factors in Postmenopausal Women by Manns, Patricia Janine; PhD from Oregon State University, 2002, 99 pages http://wwwlib.umi.com/dissertations/fullcit/3044340

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Understanding Factors Associated with Intention to Use Hormone Replacement Therapy among Thai Middle-aged Women by Burusanont, Montarat; PhD from University of Minnesota, 2002, 192 pages http://wwwlib.umi.com/dissertations/fullcit/3039636

Dissertations 141

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Women's Ways of Speaking about Menopause and Hormone Replacement Therapy: an American Discourse on Personhood by Suopis, Cynthia Anne; PhD from University of Massachusetts Amherst, 2002, 274 pages http://wwwlib.umi.com/dissertations/fullcit/3056283

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.

143

CHAPTER 5. CLINICAL REPLACEMENT THERAPY

TRIALS

AND

HORMONE

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hormone replacement therapy.

Recent Trials on Hormone Replacement Therapy The following is a list of recent trials dedicated to hormone replacement therapy.8 Further information on a trial is available at the Web site indicated. •

Development and Evaluation of a Hormone Replacement Therapy Decision-Aid Condition(s): Menopause Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: The decision regarding the use of post-menopausal estrogen hormone replacement therapy (HRT) is complex because patients must balance the short- and long-term risks and benefits. Information from new and important clinical trials must also be considered. The purpose of this research is to develop and evaluate the efficacy of a HRT CD-ROM decision-aid in improving the decision-making process for women considering the use of estrogen HRT. The objectives of the study are to: 1) develop a model of the decision-making process for women considering estrogen hormone replacement therapy (HRT), based on Multi-Attribute Utility Theory (MAUT); 2) produce an interactive CD-ROM decision-aid for HRT; 3) evaluate the effect of the interactive CD-ROM decision-aid on patient satisfaction with decision (SWD) and knowledge about menopause and HRT; and 4) test the effect of the interactive CD-ROM decision-aid on women's decisions regarding initiation of HRT. Phase I (completed) used structured interviews and surveys in the development of a decision model for HRT. In phase II, an interactive CD-ROM decision-aid was developed and a randomized controlled trial (RCT) of its effect on decision processes was initiated. Postmenopausal

8

These are listed at www.ClinicalTrials.gov.


women, aged 45-74, are being recruited from the primary care clinics of the four participating Veterans Affairs hospitals: Milwaukee, Madison, Chicago-Hines, and Chicago-Westside. The primary hypothesis is that women who use the CD-ROM decision-aid will demonstrate increased satisfaction with their decision regarding hormone replacement therapy use compared to women receiving the control intervention. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012909 •

Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer Condition(s): menopausal symptoms; stage I breast cancer; stage II breast cancer; breast cancer in situ Study Status: This study is currently recruiting patients. Sponsor(s): Regional Oncologic Center; Scandinavian Breast Group; International Breast Cancer Study Group; EORTC Breast Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer. PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003771

•

Randomized Study of Oral Contraceptives or Hormone Replacement Therapy in Women With Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Determine the effect of oral contraceptives containing low-dose synthetic estrogens and progestins on disease activity in premenopausal women with inactive, stable, or moderate systemic lupus erythematosus (SLE). II. Determine the effect of hormone replacement therapy with conjugated estrogens and progestins on disease activity in postmenopausal women with inactive, stable, or moderate SLE. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006133

Clinical Trials 145

•

Hormone Replacement Therapy and Prothrombotic Variants Condition(s): Cardiovascular Diseases; Heart Diseases; Cerebrovascular Accident; Myocardial Infarction; Hypertension Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine in postmenopausal women the potential interactions of hormone replacement therapy with other blood clotting factors on the risk of cardiovascular diseases such as heart attack or stroke. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049933

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 “hormone replacement therapy” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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


•

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

•

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

•

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

•

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

•

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

•

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

•

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

147

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

Patents on Hormone Replacement Therapy By performing a patent search focusing on hormone replacement therapy, 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 9Adapted

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


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

11.beta.-aryl substituted 14,17-ethanoestratriens, method for the production of these compounds and their use in the production of medicaments Inventor(s): Bohlmann; Rolf (Berlin, DE), Fritzemeier; Karl Heinrich (Berlin, DE), Hegele-Hartung; Christa (Berlin, DE), Knauthe; Rudolf (Berlin, DE), Parzcyk; Karsten (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin, DE) Patent Number: 6,229,029 Date filed: June 9, 2000 Abstract: This invention describes 11.beta.-aryl-substituted 14,17-ethanoestratrienes of general formula (I). The new compounds are selective estrogens whose action occurs in a tissue-selective manner. The estrogenic action occurs in particular on bone, in the cardiovascular system and in the CNS (central nervous system). Only a slight estrogenic action or no estrogenic action occurs in the uterus and in the liver, however. The compounds are suitable for the production of pharmaceutical agents for use in numerous indications (for example for hormone replacement therapy, prevention and treatment of osteoporosis). Excerpt(s): This application is a 371 of PCT/EP98/03243 filed Jun. 2, 1998. R.sup.6 has the meaning of R.sup.4 or R.sup.5 or is an optionally substituted aryl or arylalkyl radical, whereby the alkyl radical can have up to 6 carbon atoms in it and the aryl radical alone or in the arylalkyl radical is a 5- or 6-membered monocyclic ring or a condensed 8- to 10-membered ring system, and the aryl radical can have one or more heteroatoms that are selected from among oxygen, nitrogen and sulfur. Alkyl groups that are mentioned within the scope of this invention as R.sup.4 and R.sup.5 are, for example, the methyl, ethyl, n- or iso-propyl, n-, iso- or tert-butyl, pentyl, neo-pentyl, hexyl, heptyl or octyl group. Web site: http://www.delphion.com/details?pn=US06229029__

•

Administration system for estradiol Inventor(s): Gonella; Jacques (Muttenz, CH) Assignee(s): Giapharma SA (Zug, CH) Patent Number: 5,665,377 Date filed: December 19, 1994 Abstract: The adhesive plaster for the transdermal administration of estradiol or mixture estradiol/progestin is composed of an impermeable carrier film and of an adhesive composition. The latter represents a matrix or reservoir layer and is composed of a solvent-based polyacrylate or polyisobutylene adhesive which contains a saturated or unsaturated fatty acid with 6 to 18 C atoms as permeability enhancer, estradiol or mixture estradiol/progestin as active substance and optionally propylene glycol as solvent.The adhesive plaster is used for the systemic administration of hormones in hormone replacement therapy for a time of at least 3 days.

Patents 149

Excerpt(s): The present invention relates to a percutaneous (or transdermal) administration system for estradiol, alone or in combination with a progestin. This administration system is an adhesive plaster which contains an adhesive composition which contains the active substance and which is applied to an impermeable carrier film. Sticking on the adhesive plaster results in a virtually constant rate of release of the hormone for a period of at least 3 days. The system additionally contains a permeability enhancer which reduces the resistance of the skin to diffusion of the active substance. Estradiol is the main estrogen secreted by the female gonad during the fertile years of life. At an age of 45 to 50 years the menses cease owing to a decrease in ovarian function, and women enter the so-called climacterium. The deficiency of hormone secretion leads in many women to development of vasomotor signs and symptoms (hot flushes, sweating) as well as sleep distrubances, anxiety states and atrophy of hormonecontrolled organs, such as in the mammary glands and the vaginal epithelium. These symptoms and signs are called the menopausal syndrome. In addition to this, the low level of hormone secretion likewise leads to an increase in cardiovascular disorders and the development of osteoporosis. Web site: http://www.delphion.com/details?pn=US05665377__ •

Antiprogestin cyclophasic hormonal regimen Inventor(s): Grubb; Gary S. (Bridgewater, NJ) Assignee(s): Ortho Pharmaceitical Corporation (Raritan, NJ) Patent Number: 5,521,166 Date filed: December 19, 1994 Abstract: The present invention is directed to cyclophasic hormonal regimens which comprise antiprogestin and progestin for human contraception whereby progestin is administered in the alternating presence and absence of an antiprogestin in effective amounts to upregulate steroid receptor levels or is alternatively dosed with effective amounts of antiprogestin to upregulate steroid receptor levels. The present invention also provides an estrogen containing cyclophasic hormonal regimen for climacteric or menopausal hormone replacement therapy comprising the administration of an effective hormone replacement amount of estrogen in alternating doses with a combined amount of estrogen and an effective amount of antiprogestin to inhibit proliferation of endometrial tissue caused by the administration of the estrogen. Excerpt(s): The present invention is directed to cyclophasic hormonal regimens for contraception and hormone replacement therapy. More particularly, the present invention is directed to cyclophasic hormonal regimens which comprise antiprogestin and progestin for human contraception whereby progestin is continuously administered in the alternating addition and absence of an antiprogestin in effective amounts to upregulate steroid receptor levels or progestin is administered in alternating doses with effective amounts of antiprogestin to upregulate steroid receptor levels. The present invention also provides an estrogen containing cyclophasic hormonal regimen for climacteric or menopausal hormone replacement therapy comprising the administration of an effective hormone replacement amount of estrogen in alternating doses with a combined amount of estrogen and an effective amount of antiprogestin to inhibit proliferation of endometrial tissue caused by the administration of the estrogen. The concept of cyclophasic hormonal regimens comprising estrogens and progestins is disclosed by Robert Casper in U.S. Pat. Nos. 5,108,995; 5,256,421; and 5,276,022. The disclosures of these three U.S. Patents are hereby incorporated herein by reference. The


primary aim of both the oral contraception (OC) hormone replacement therapy (HRT) and cyclophasic regimens disclosed by Casper is to induce higher levels of progestin and estrogen receptors by an estrogen-induced increase in receptor production. The greater concentration of steroid receptors increases the sensitivity of the target organs to progestin and estrogen and allows the use of lower doses of exogenous steroids. The cyclophasic regimens of Casper upregulate the estrogen and progestin receptors in an estrogen-dominant phase of 2-4 days and then down-regulate the same receptors in a progestin-dominant phase in the next 2-4 days. In contrast to conventional oral contraception regimens which are continuously progestin-dominant, the levels of the estrogen and progestin receptors are continuously down-regulated. In both phases of the cyclophasic regimen, the estrogen dose is constant while the progestin dose is varied to produce relatively progestin-dominant or estrogen-dominant effects. These alternating phases continue without interruption for HRT but with OC, they are interrupted periodically for 4-7 days to allow menstrual bleeding to occur. Web site: http://www.delphion.com/details?pn=US05521166__ •

COMBINATION OF PROSTACYCLIN WITH AN ESTROGEN OR PROGESTIN FOR THE PREVENTION AND TREATMENT OF ATHEROSCLEROTIC VASCULAR DISEASE INCLUDING PREECLAMPSIA AND FOR THE TREATMENT OF HYPERTENSION, AND FOR HORMONE REPLACEMENT THERAPY Inventor(s): Chwalisz; Kristof (Berlin, DE), Garfield; Robert E. (Friendswood, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 6,613,757 Date filed: September 22, 1994 Abstract: Cardiovascular disease, including preeclampsia in pregnant women and hypertension in both women and men, are prevented or treated by administering thereto prostacyclin or a prostacyclin analog in combination with one or both of an estrogen and a progestin, which combination is also useful for HRT in peri- and postmenopausal women. Excerpt(s): This invention relates to a method for the prevention and treatment of atherosclerotic vascular disease (cardiovascular disease); for the prevention and treatment preeclampsia in pregnant women and for hormone replacement therapy in peri- and post-menopausal women, and for the treatment of hypertension in women and men. Epidemiological data indicate that approximately one half of the deaths in economically developed countries are attributable to a single major cause, viz., cardiovascular disease, including coronary heart disease, stroke and other forms of vascular disease (Green, A., Bain, C., 1993). The commonest and most lethal form of cardiovascular disease is coronary heart disease. In men, there is a continuous increase in the prevalence of cardiovascular disease after the age of 30-40 years. On the other hand, the rate of cardiovascular disease, especially coronary heart disease, is relatively low among premenopausal women but rises sharply with increasing age, suggesting that sex steroids (estrogens and progesterone) have a protective effect in women. The increased risk of coronary heart disease among women with bilateral oophorectomy further supports the view that steroid hormones may play a protective role with regard to cardiovascular disease. Cardiovascular disease can be prevented in postmenopausal women by hormone replacement therapy (HRT) with estrogens. The recently performed meta-analysis of 29 studies has demonstrated a reduced cardiovascular

Patents 151

disease risk among estrogen users in 23 of these studies (Stampfer et al., 1991). There is also experimental evidence from studies in monkeys that the development of coronary atherosclerosis induced by oophorectomy and diet may be reversed by estrogen supplementation (Adams et al., 1992). On the other hand, there are no effective methods for the prevention of cardiovascular disease in man, since estrogen cannot be used because of side-effects. Web site: http://www.delphion.com/details?pn=US06613757__ •

Combined pharmaceutical estrogen-androgen-progestin Inventor(s): Hughes, Jr.; Claude L. (Simi Valley, CA), Jayo; Manuel J. (Advance, NC) Assignee(s): Cedars-Sinai Medical Center (Los Angeles, CA), Wake Forest University (Winston-Salem, NC) Patent Number: 6,139,873 Date filed: October 23, 1998 Abstract: Disclosed are methods and compositions for oral contraception and for hormone replacement therapy. Certain compositions of the invention contain androgens, preferably methyltestosterone to be taken in conjunction with estrogens and progestins. Excerpt(s): The present invention relates generally to the field of pharmaceutical preparations and in particular to the field of oral contraceptives and hormone replacement therapy. In particular the present invention addresses the field of peak bone mass accrual in young oral contraceptive users and restoration of normal hormonal balance in women of any age in need thereof. Due to the relatively high rate of teenage pregnancy in the United States, pediatric and adolescent gynecologists often recommend that young women take some form of contraception to prevent unwanted pregnancies (The Contraception Report, 1995). The most common method of contraception among adolescents is oral contraceptives, taken by approximately 46% of the sexually active population. Consequently, almost half of all premenopausal women (

Hormone Replacement Therapy - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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Hormone Replacement Therapy - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Growth Hormone Deficiency - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Follicle-Stimulating Hormone - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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

Radiation Therapy. A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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

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

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

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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