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

66 Scopus citations


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
Issue number2
StatePublished - Feb 1 2018

Bibliographical note

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.


Dive into the research topics of 'The effect of testosterone on cardiovascular biomarkers in the testosterone trials'. Together they form a unique fingerprint.

Cite this