The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men

Peter J. Snyder, Susan S. Ellenberg, Glenn R. Cunningham, Alvin M. Matsumoto, Shalender Bhasin, Elizabeth Barrett-Connor, Thomas M. Gill, John T. Farrar, David Cella, Raymond C. Rosen, Susan M. Resnick, Ronald S. Swerdloff, Jane A. Cauley, Denise Cifelli, Laura Fluharty, Marco Pahor, Kristine E. Ensrud, Cora E. Lewis, Mark E. Molitch, Jill P. CrandallChristina Wang, Matthew J. Budoff, Nanette K. Wenger, Emile R. Mohler, Diane E. Bild, Nakela L. Cook, Tony M. Keaveny, David L. Kopperdahl, David Lee, Ann V. Schwartz, Thomas W. Storer, William B. Ershler, Cindy N. Roy, Leslie J. Raffel, Sergei Romashkan, Evan Hadley

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation.

Original languageEnglish (US)
Pages (from-to)362-375
Number of pages14
JournalClinical Trials
Volume11
Issue number3
DOIs
StatePublished - Jun 2014

Bibliographical note

Funding Information:
The Testosterone Trials were supported by a grant from the National Institute on Aging, National Institutes of Health (U01 AG030644), supplemented by funds from the National Heart, Lung and Blood Institute, National Institute of Neurological Diseases and Stroke, and National Institute of Child Health and Human Development. The Bone Trial was supported by a grant from the National Institute on Aging (R01 AG037679). The Anemia Trial was supported by a grant from the National Institute on Aging, National Institutes of Health (U01 AG034661) to the Partnership for Anemia Clinical and Translational Trials in the Elderly consortium. AbbVie (formerly Solvay and Abbott Laboratories) generously provided funding, AndroGel, and placebo gel. A.M.M. was supported by the Department of Veterans Affairs Puget Sound Health Care System. T.M.G. was the recipient of a Midcareer Investigator Award in Patient-Oriented Research (K24-AG021507) and is the recipient of an Academic Leadership Award (K07AG043587), both from the National Institute on Aging. The Yale Field Center was partially supported by the Claude D. Pepper Older Americans Independence Center (P30-AG021342). S.M.R. was supported by the Intramural Research Program, National Institute on Aging, National Institutes of Health. C.E.L. was supported by the National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health (DK079626) to the UAB Diabetes Research and Training Center. J.A.C. was supported by the National Institute on Aging, National Institutes of Health (R01 AG37679).

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

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