Due to increased marketing, rates of testosterone prescription in the U.S. tripled between 2000 and 2011…
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Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.
To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease.
Design, Setting, and Patients:
A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011.
Main Outcomes and Measures:
Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke.
Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%) at 3 years after coronary angiography. In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41).
Conclusions and Relevance:
Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
Rates of testosterone therapy prescription have increased markedly in the United States over the past decade. Annual prescriptions for testosterone increased by more than 5-fold from 2000 to 2011, reaching 5.3 million prescriptions and a market of $1.6 billion in 2011. Professional society guidelines recommend testosterone therapy for patients with symptomatic testosterone deficiency. In addition to improving sexual function and bone mineral density and increasing free-fat mass and strength treatment with testosterone has been shown to improve lipid profiles and insulin resistance and increase the time to ST depression during stress testing.
The effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. Prior clinical studies of testosterone therapy have not detected adverse cardiac events, but these trials were generally focused on intermediate end points, of short duration, and not powered for clinical end points. A recent trial, the Testosterone in Older Men with Mobility Limitations (TOM) trial, conducted in older frail men with a high prevalence of cardiovascular diseases was stopped prematurely due to increased cardiovascular events in the treatment group. The premature termination of the TOM trial and the limitations of the prior studies highlight uncertainty regarding the safety of testosterone therapy in older men with cardiovascular diseases.
To address this gap in knowledge, we evaluated the association between the use of testosterone therapy and all-cause mortality, myocardial infarction (MI), and stroke among male veterans and whether this association was modified by underlying coronary artery disease (CAD).