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Randomized Controlled Trial
. 2017 Feb 21;317(7):708-716.
doi: 10.1001/jama.2016.21043.

Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone

Matthew J Budoff  1 , Susan S Ellenberg  2 , Cora E Lewis  3 , Emile R Mohler 3rd  4 , Nanette K Wenger  5 , Shalender Bhasin  6 , Elizabeth Barrett-Connor  7 , Ronald S Swerdloff  8 , Alisa Stephens-Shields  2 , Jane A Cauley  9 , Jill P Crandall  10 , Glenn R Cunningham  11 , Kristine E Ensrud  12 , Thomas M Gill  13 , Alvin M Matsumoto  14 , Mark E Molitch  15 , Rine Nakanishi  1 , Negin Nezarat  1 , Suguru Matsumoto  1 , Xiaoling Hou  2 , Shehzad Basaria  6 , Susan J Diem  16 , Christina Wang  8 , Denise Cifelli  2 , Peter J Snyder  17
Affiliations
Randomized Controlled Trial

Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone

Matthew J Budoff et al. JAMA. .

Abstract

Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk.

Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume.

Design, setting, and participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014.

Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.

Main outcomes and measures: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis).

Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group.

Conclusions and relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.

Trial registration: clinicaltrials.gov Identifier: NCT00799617.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Budoff reported receiving a grant from General Electric. Dr Ellenberg reported receiving a grant from AbbVie. Dr Mohler reported serving as a consultant to Clarus Therapeutics and AbbVie. Dr Wenger reported receiving grants from Alnylam Pharmaceuticals, National Heart, Lung, and Blood Institute, Pfizer, and Society for Women’s Health Research; grants and personal fees from Gilead Sciences; and personal fees from Amgen, AstraZeneca, and Merck. Dr Bhasin reported receiving grants administered by Brigham and Women’s Hospital from AbbVie, Lilly, Transition Therapeutics, and Regeneron; receiving consulting fees from AbbVie, Lilly, and Regeneron; having a patent pending on a free testosterone calculator; and having equity interest in FPT, LLC. Dr Swerdloff reported receiving grants from Clarus Therapeutics, Lipocine, and Antares; and serving as a consultant to Clarus Therapeutics and Antares. Dr Cunningham reported serving as a consultant to AbbVie, Apricus, Besins, Clarus Therapeutics, Endo Pharma, Ferring, and Repros Therapeutics; and serving on advisory boards for AbbVie, Apricus, Clarus Therapeutics, Endo Pharma, Ferring, Lilly, Pfizer, and Repros Therapeutics. Dr A. M. Matsumoto reported receiving research support from AbbVie; receiving consulting fees from AbbVie, Endo, Lilly, the US Anti-Doping Agency, and Lipocine; receiving personal fees from Clarus Therapeutics; receiving royalties from UpTo Date; and serving on the scientific advisory board for the Partnership for Clean Competition. Dr Molitch reported serving as a consultant to AbbVie (Abbott Laboratories), Eli Lilly & Co, and Pfizer. Dr Basaria reported serving as a consultant to Eli Lilly and Takeda Pharmaceuticals. Dr Wang reported receiving research support from Clarus Therapeutics, Lipocine, Antares, and Besins; and serving on advisory committees for Lipocine, Antares, Teso RX, and Besins. Dr Snyder reported serving as a consultant to Watson Laboratories. No other disclosures were reported.

Figures

Figure
Figure. Screening and Retention of Participants in the Cardiovascular Trial
CCTA indicates coronary computed tomographic angiography; eGFR, estimated glomerular filtration rate; and TTrials, Testosterone Trials. aReasons unknown; no assessment form submitted. bSome men had more than 1 reason.
See this image and copyright information in PMC

Comment in

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