Emile R Mohler1, Susan S Ellenberg2, Cora E Lewis3, Nanette K Wenger4, Matthew J Budoff5, Michael R Lewis6, Elizabeth Barrett-Connor7, Ronald S Swerdloff8, Alisa Stephens-Shields2, Shalender Bhasin9, Jane A Cauley10, Jill P Crandall11, Glenn R Cunningham12, Kristine E Ensrud13,14, Thomas M Gill15, Alvin M Matsumoto16,17, Mark E Molitch18, Marco Pahor19, Peter E Preston2, Xiaoling Hou2, Denise Cifelli2, Peter J Snyder20. 1. Section of Vascular Medicine, Division of Cardiovascular Disease, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania. 2. Division of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania. 3. Division of Preventive Medicine, The University of Alabama at Birmingham, Birmingham, Alabama. 4. Department of Medicine, Division of Cardiology, Emory Heart and Vascular Center, Emory University School of Medicine, Atlanta, Georgia. 5. Los Angeles Biomedical Research Institute, Division of Cardiology, Harbor?University of California at Los Angeles Medical Center, Torrance, California. 6. Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont. 7. Department of Family and Preventive Medicine, Division of Epidemiology, University of California, San Diego School of Medicine, La Jolla, California. 8. Los Angeles Biomedical Research Institute, Division of Endocrinology, Harbor?University of California at Los Angeles Medical Center, Torrance, California. 9. Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. 10. Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania. 11. Divisions of Endocrinology and Geriatrics, Albert Einstein College of Medicine, Bronx, New York. 12. Departments of Medicine and Molecular & Cellular Biology, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine and Baylor St. Luke's Medical Center, Houston, Texas. 13. Department of Medicine, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota. 14. Minneapolis VA Health Care System, Minneapolis, Minnesota. 15. Section of Geriatric Medicine, Yale School of Medicine, New Haven, Connecticut. 16. Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, Puget Sound Health System, University of Washington School of Medicine, Seattle, Washington. 17. Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington. 18. Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 19. Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida. 20. Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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 (adjusted mean difference, -6.1 mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, -2.0 mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjusted mean difference, -2.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, -1.7 µIU/mL; P = 0.02) and homeostatic model assessment‒insulin resistance (adjusted mean difference, -0.6; 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 older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers, markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.
RCT Entities:
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 (adjusted mean difference, -6.1 mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, -2.0 mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjusted mean difference, -2.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, -1.7 µIU/mL; P = 0.02) and homeostatic model assessment‒insulin resistance (adjusted mean difference, -0.6; 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 older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers, markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.
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