Testosterone therapy may increase the risk of adverse cardiovascular events and all-cause mortality, according to findings published Nov. 5 in the Journal of the American Medical Association .

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The retrospective analysis included 8,709 men in the Veterans Affairs system with testosterone levels below 300 ng/dL who underwent coronary angiography between 2005 and 2011. Testosterone therapy was prescribed to 1,223 patients, and patients were followed for an average of 27.5 months for the incidence of a composite endpoint of all-cause mortality, myocardial infarction (MI) and stroke.

Although patients who received and did not receive testosterone therapy were young (mean age 60.6 and 63.8 years, respectively, p<0.001), there was a high overall prevalence of comorbidities. Twenty percent of patients had a history of MI, 50 percent had diabetes and more than 80 percent had coronary artery disease (CAD). Three years following coronary angiography, the absolute event rates were 25.7 percent in the testosterone group and 19.9 percent in the no-testosterone group, an absolute risk difference of 5.8 percent (95 percent CI, -1.4 percent to 13.1 percent). The increased risk persisted after adjustment for the presence of coronary artery disease.

The investigators concluded that the "use of testosterone therapy in this cohort of veterans with significant medical comorbidities was associated with increased risk of mortality, MI or ischemic stroke." They add that the findings were not altered by the presence of CAD. Moving forward, they note that "future studies, including randomized controlled trials, are needed to properly characterize the potential risks of testosterone therapy in men with comorbidities."

However, the investigators also noted that the retrospective design of the study may introduce bias and unaccounted for confounding variables, and cautioned that results may not be generalizable.

In an editorial comment, Anne R. Cappola, MD, University of Pennsylvania, Philadelphia, notes, "Perhaps the most important question is the generalizability of the results of this study to the broader population of men taking testosterone: men of this age group who are taking testosterone for 'low T syndrome' or for anti-aging purposes and younger men taking it for physical enhancement. Does the 29 percent increased risk of myocardial infarction, ischemic stroke or mortality apply to these groups?"

She adds that, "In light of the high volume of prescriptions and aggressive marketing by testosterone manufacturers, prescribers and patients should be wary. There is mounting evidence of a signal of cardiovascular risk."

Keywords: Risk, Stroke, Myocardial Infarction, Coronary Artery Disease, Comorbidity, Prevalence, Incidence, Confounding Factors, Epidemiologic, Veterans, Coronary Angiography, Cardiovascular Diseases, Diabetes Mellitus, Testosterone

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