The effect of testosterone on cardiovascular biomarkers in the testosterone trials

Emile R. Mohler, Susan S. Ellenberg, Cora E. Lewis, Nanette K. Wenger, Matthew J. Budoff, Michael R. Lewis, Elizabeth Barrett-Connor, Ronald S. Swerdloff, Alisa Stephens-Shields, Shalender Bhasin, Jane A. Cauley, Jill P. Crandall, Glenn R. Cunningham, Kristine E. Ensrud, Thomas M. Gill, Alvin M. Matsumoto, Mark E. Molitch, Marco Pahor, Peter E. Preston, Xiaoling HouDenise Cifelli, Peter J. Snyder

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Context: Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective: To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design: Double-blind, placebo-controlled trial. Setting: Twelve academic medical centers in the United States. Participants: In all, 788 men > 65 years old with an average of two serum testosterone levels ,275 ng/dL who were enrolled in The Testosterone Trials. Intervention: Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcome Measures: Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Results: Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjustedmean difference,26.1mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, 22.0mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjustedmean difference, 22.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, 21.7 mIU/mL; P = 0.02) and homeostatic model assessment insulin resistance (adjusted mean difference, 20.6; P = 0.03). Testosterone did not change triglycerides, D-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Conclusions and Relevance: Testosterone treatment of 1 year in oldermen with lowtestosteronewas associated withsmall reductions in cholesterol and insulin but not with other glucosemarkers,markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.

Original languageEnglish (US)
Pages (from-to)681-688
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number2
DOIs
StatePublished - Feb 1 2018

Bibliographical note

Funding Information:
S.S.E. reports grants from the National Institutes of Health (NIH) and from AbbVie, Inc, and during the conduct of the study, grants from AbbVie, Inc. Outside the submitted work, C.E.L. reports grants from the NIH and grants from AbbVie. During the conduct of the study, N.K.W. reports grants from Alnylam Pharmaceuticals, grants and personal fees from Gilead Sciences, grants from the NHLBI, grants from Pfizer, grants from the Society for Women’s Health Research, personal fees from Amgen, personal fees from AstraZeneca, and personal fees from Merck. Outside the submitted work, M.J.B. reports grants from the NIH and during the conduct of the study, grants from General Electric. Outside the submitted work, E.B.-C. has nothing to disclose. R.S.S. reports grants from The Bone Trial of the Testosterone Trial during the conduct of the study, grants and other from Clarus, grants from Lipesene, and grants and other from Antares. Outside the submitted work, A.S.-S. reports grants from the National Institute on Aging and from AbbVie during the conduct of the study. S.B. reports grants from the NIA during the conduct of the study and grants and personal fees from AbbVie, grants and personal fees from Lilly, grants from Transition Therapeutics, and grants and personal fees from Regeneron outside the submitted work. In addition, S.B. has a patent free testosterone calculator pending and has equity interest in FPT, LLC. J.A.C. has nothing to disclose. J.P.C. has nothing to disclose. G.R.C. reports personal fees from AbbVie, Clarus Therapeutics, Endo Pharma, Ferring, Lilly, Merck, Pfizer, and Repros Therapeutics. Outside the submitted work, K.E.E. reports grants from the National Institute on Aging. During the conduct of the study, T.M.G. reports grants from the National Institute on Aging. During the course of the study, A.M.M. reports personal fees from AbbVie, Endo, Lilly, Lipocine, Clarus, and AYTU. Outside the submitted work, M.E.M. reports grants from the NIH, grants from Abbott Laboratories, and during the conduct of the study, personal fees from AbbVie (Abbott Laboratories), personal fees from Eli Lilly & Co., and personal fees from Pfizer. Outside the submitted work, X.H. has nothing to disclose. D.C. has nothing to disclose. P.J.S. reports grants from the National Institute on Aging and NIH and grants and nonfinancial support from AbbVie (formerly Solvay and Abbott Laboratories) during the conduct of the study. M.R.L., M.P., and P.E.P. have nothing to disclose.

Funding Information:
Financial Support: The Testosterone Trials were supported by a grant from the National Institute on Aging, National Institutes of Health (U01 AG030644) (to P.J.S.), supplemented by funds from the National Heart, Lung and Blood Institute, National Institute of Neurologic Diseases and Stroke, and National Institute of Child Health and Human Development. AbbVie (formerly Solvay and Abbott Laboratories) generously provided funding, AndroGel, and placebo gel. UAB Diabetes Research and Training Center (DRCT), Grant DK-079626 from the National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health (to C.E.L.); funding for the Rancho Bernardo Study has been supported by National Institutes of Health/National Institute on Aging grants AG07181 and AG028507 and the National Institute of Diabetes and Digestive and Kidney Diseases, Grants DK31801 (to E.B.-C.), T32-DK007571 (to R.S.S.), and U01-AG030644 (main) and 5 R01 AG37679 (bone) (to J.A.C.). T.M.G. is the recipient of Academic Leadership Award K07AG043587 from the National Institute on Aging. The Yale Field Center is partially supported by the Claude D. Pepper Older Americans Independence Center (Grant P30AG021342). A.M.M. was supported by Department of Veterans Affairs Puget Sound Health Care System Grant U01-AG030644.

Funding Information:
Disclosure Summary: E.R.M. reports grants from Clarus Pharmaceuticals and AbbVie. Outside the submitted work,

Publisher Copyright:
Copyright © 2018 Endocrine Society.

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