Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels

Study Questions:

What is the association between the use of testosterone therapy and adverse cardiovascular outcomes among male veterans?

Methods:

This was a retrospective analysis of men with low testosterone levels (<300 ng/dl) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. Using pharmacy dispensing data, patients were categorized as initiating testosterone therapy (gel, patch, or injections); patients who started therapy prior to angiography were excluded. Cox proportional hazards were used to assess the association between testosterone therapy and the primary outcomes (composite of time to all-cause mortality or hospitalization for myocardial infarction or ischemic stroke). The authors performed adjusted analyses to test for an interaction between coronary artery disease (defined as having a 20% or greater stenosis in any epicardial vessel prior to the initiation of testosterone therapy) and testosterone therapy.

Results:

Of 8,709 patients with low testosterone levels, 1,223 (14.0%) initiated testosterone therapy. The absolute rate of events among those patients not receiving testosterone therapy, compared to those who received testosterone therapy, was 19.9% versus 25.7% at 3 years from coronary angiography. The absolute risk difference was 5.8% (95% confidence interval, -1.4% to 13.1%) at 3 years. In adjusted analyses, testosterone was associated with increased risk of adverse cardiovascular outcomes (hazard ratio, 1.29; 95% confidence interval, 1.05-1.58; p = 0.02); this risk was unchanged after adjusting for coronary artery disease.

Conclusions:

In patients with and without coronary artery disease, testosterone therapy is associated with all-cause mortality, myocardial infarction, and ischemic stroke.

Perspective:

The findings from this analysis raise safety concerns about the use of testosterone therapy. If testosterone therapy is considered or prescribed for symptomatic relief, providers should disclose that there is uncertainty about long-term risks and that treatment may be harmful. Further studies should clarify these long-term risks and elucidate the mechanisms through which testosterone therapy may be harmful.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Uncertainty, Constriction, Coronary Artery Disease, Stroke, Myocardial Infarction, Plaque, Atherosclerotic, Cardiovascular System, Risk Factors, Veterans, Coronary Angiography, Cardiovascular Diseases, Confidence Intervals, Hormone Replacement Therapy, Testosterone


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