Testosterone and Aging: Clinical Research Directions

238 Pages·2004·3.72 MB·English

Committee on Assessing the Need for Clinical Trials
of Testosterone Replacement Therapy
Board on Health Sciences Policy
Catharyn T. Liverman and Dan G. Blazer, Editors
THE NATIONAL ACADEMIES PRESS • 500 Fifth Street, N.W. • Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Gov-
erning Board of the National Research Council, whose members are drawn from
the councils of the National Academy of Sciences, the National Academy of Engi-
neering, and the Institute of Medicine. The members of the committee responsible
for the report were chosen for their special competences and with regard for ap-
propriate balance.
Support for this project was provided by the National Institute on Aging and the
National Cancer Institute. The views presented in this report are those of the Insti-
tute of Medicine Committee on Assessing the Need for Clinical Trials of Testoster-
one Replacement Therapy and are not necessarily those of the funding agencies.
Library of Congress Cataloging-in-Publication Data
Testosterone and aging : clinical research directions / Committee on Assessing
the Need for Clinical Trials of Testosterone Replacement Therapy, Board on Health
Sciences Policy ; Catharyn T. Liverman, Dan G. Blazer, editors.
p. ; cm.
Includes bibliographical references.
ISBN 0-309-09063-6 (pbk.); 0-309-52720-1 (PDF)
1. Longevity. 2. Aging—Prevention. 3. Testosterone—Physiological effect.
[DNLM: 1. Aging—drug effects. 2. Testosterone—physiology. 3. Testosterone—
therapeutic use—Aged. WT 104 T3455 2004] I. Liverman, Catharyn T. II. Blazer,
Dan G. (Dan German), 1944- III. National Research Council (U.S.). Committee on
Assessing the Need for Clinical Trials of Testosterone Replacement Therapy.
RA776.75.T45 2004
612.6’8—dc22
2003026323
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COMMITTEE ON ASSESSING THE NEED FOR CLINICAL TRIALS
OF TESTOSTERONE REPLACEMENT THERAPY
DAN G. BLAZER, (Chair), J.P. Gibbons Professor of Psychiatry and
Behavioral Sciences, Duke University Medical Center, Durham,
North Carolina
ELIZABETH BARRETT-CONNOR, Chief, Division of Epidemiology,
University of California, San Diego
BARUCH A. BRODY, Director, Center for Medical Ethics and Health
Policy, Baylor College of Medicine, Houston, Texas
ROBERT M. CALIFF, Director, Duke Clinical Research Unit, Duke
University Medical Center, Durham, North Carolina
JOSEPH P. COSTANTINO, Professor, Department of Biostatistics,
Graduate School of Public Health, University of Pittsburgh,
Pennsylvania
DANIEL D. FEDERMAN, Senior Dean, Alumni Relations and Clinical
Teaching, Harvard Medical School, Boston, Massachusetts
LINDA P. FRIED, Professor, Schools of Medicine and Public Health,
Director, Center on Aging and Health, Director, Division of
Geriatric Medicine and Gerontology, Johns Hopkins Medical
Institutions, Baltimore, Maryland
DEBORAH G. GRADY, Professor, School of Medicine, University of
California, San Francisco
WILLIAM R. HAZZARD, Professor, School of Medicine, University of
Washington, Seattle
STEVEN B. HEYMSFIELD, Professor, School of Medicine, Columbia
University College of Physicians and Surgeons, New York
STEPHEN W. LAGAKOS, Henry Pickering Walcott Professor and
Chairman of Biostatistics, Harvard School of Public Health, Boston,
Massachusetts
MARK S. LITWIN, Professor, David Geffen School of Medicine and
School of Public Health, University of California, Los Angeles
PAUL A. LOMBARDO, Associate Professor and Director, Program in
Law and Medicine, University of Virginia, Charlottesville
PETER S. NELSON, Associate Professor, Fred Hutchinson Cancer
Research Center, Seattle, Washington
ERIC S. ORWOLL, Program Director, General Clinical Research Center,
Oregon Health and Science University, Portland
LESLIE R. SCHOVER, Associate Professor, M.D. Anderson Cancer
Center, University of Texas, Houston
E. DARRACOTT VAUGHAN, JR., Chairman Emeritus, Department of
Urology, Weill Medical College of Cornell University, New York
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Board on Health Sciences Policy Liaison
Leslie Benet, Chairman, Department of Biopharmaceutical Sciences,
University of California, San Francisco
IOM Project Staff
Catharyn T. Liverman, Study Director
Benjamin Hamlin, Research Assistant
Judith L. Estep, Senior Project Assistant
IOM Board on Health Sciences Policy Staff
Andrew M. Pope, Director
Troy Prince, Administrative Assistant
Carlos Gabriel, Financial Associate
vi
Independent Report Reviewers
This report has been reviewed in draft form by individuals chosen
for their diverse perspectives and technical expertise, in accordance
with procedures approved by the NRC’s Report Review Commit-
tee. The purpose of this independent review is to provide candid and criti-
cal comments that will assist the institution in making its published re-
port as sound as possible and to ensure that the report meets institutional
standards for objectivity, evidence, and responsiveness to the study
charge. The review comments and draft manuscript remain confidential
to protect the integrity of the deliberative process. We wish to thank the
following individuals for their review of this report:
John H. J. Bancroft, The Kinsey Institute for Research in Sex, Gender
and Reproduction, Indiana University
Jeri S. Janowsky, Department of Neurology, Oregon Health and Science
University
Curtis L. Meinert, Center for Clinical Trials, Johns Hopkins Bloomberg
School of Public Health
Jonathan D. Moreno, Center for Biomedical Ethics, University of
Virginia
Peter J. Snyder, School of Medicine, University of Pennsylvania
David H. Solomon, University of California, Los Angeles
Marcia L. Stefanick, Stanford University School of Medicine
Patrick C. Walsh, Brady Urological Institute, Johns Hopkins Hospital
Christina Wang, Department of Medicine, Harbor-UCLA Medical
Center
Kristine Yaffe, School of Medicine, University of California, San
Francisco
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viii INDEPENDENT REPORT REVIEWERS
Although the reviewers listed above have provided many construc-
tive comments and suggestions, they were not asked to endorse the con-
clusions or recommendations, nor did they see the final draft of the report
before its release. The review of this report was overseen by Robert B.
Wallace, Professor of Epidemiology and Internal Medicine, College of
Public Health, University of Iowa. Appointed by the National Research
Council and Institute of Medicine, he was responsible for making certain
that an independent examination of this report was carried out in accor-
dance with institutional procedures and that all review comments were
carefully considered. Responsibility for the final content of this report rests
entirely with the authoring committee and the institution.
Preface
In the popular literature, testosterone has been linked with youth,
vitality, and strength. These perceptions seem to fuel interest in the
use of testosterone as a means of delaying or averting the effects of
aging, as is evident by the growing numbers of middle-aged and older
men using testosterone products.
In November 2002, the National Institute on Aging and the National
Cancer Institute requested that the Institute of Medicine conduct a study
to provide an independent assessment of clinical research on testosterone
therapy and make recommendations on future research directions for this
field.
As the committee examined the state of research on testosterone
therapy, it was struck by the paucity of randomized controlled clinical
trials, particularly in middle-aged or older men. Those clinical trials that
have been conducted are generally of short duration and involved small
numbers of participants. In some ways this is not surprising, as testoster-
one products have been approved by the Food and Drug Administration
primarily to treat hypogonadism, a medical condition that can occur in
younger men and involves markedly low levels of testosterone and other
symptoms. Many of the studies of testosterone therapy to date have thus
been in young hypogonadal males. Further, conducting clinical trials of
testosterone therapy in older men is fraught with complexities, particu-
larly considerations regarding the potential effects of testosterone on the
prostate gland and other potential adverse health outcomes.
The committee’s task was to identify the research needed to deter-
mine if testosterone is an efficacious treatment option for older men. This
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