Testosterone therapy may raise MI, stroke risk

Among a group of men who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of death, heart attack, or ischemic stroke, according to a recent study.

First author Rebecca Vigen, MD, of the University of Texas Southwestern Medical Center, Dallas and colleagues 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).

The study, which was published in JAMA (2013; 310:1829-36), included 8,709 men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs system between 2005 and 2011. There was a high level of co-existing illnesses among this group, including prior history of heart attack, diabetes, or CAD. Of the 8,709 patients, 1,223 (14%) initiated testosterone therapy after a median of 531 days following angiography. The average follow-up was approximately 2.5 years. The primary measured outcome for the study was a composite of all-cause mortality, MI, and ischemic stroke.

The authors found that the proportion of patients experiencing events 3 years after coronary angiography was 19.9% in the no testosterone therapy group (average age, 64 years) and 25.7% in the testosterone therapy group (average age, 61 years), for an absolute risk difference of 5.8%.

Even accounting for other factors that could explain the differences, use of testosterone therapy was associated with adverse outcomes and was consistent among patients with and without CAD. The increased risk of adverse outcomes associated with testosterone therapy use was not related to differences in risk factor control or rates of secondary prevention medication use because patients in both groups had similar blood pressure, low-density lipoprotein levels, and use of secondary prevention medications, according to the authors.

“These findings raise concerns about the potential safety of testosterone therapy. Future studies including randomized controlled trials are needed to properly characterize the potential risks of testosterone therapy in men with comorbidities,” the authors wrote.

In an accompanying editorial (JAMA 2013; 310:1805-6), Anne R. Cappola, MD, ScM, of the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, wrote, “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, to which the study by Vigen et al contributes. This signal warrants both cautious testosterone prescribing and additional investigation.”

Dr. Cappola notes that additional information from an ongoing study known as the T Trial-a randomized trial of 800 men aged 65 and older with diminished walking ability, interest in sex, energy, memory, or iron levels in blood who will receive testosterone gel or placebo for 1 year-may provide important guidance to older men who meet current recommendations for testosterone therapy.

Dr. Cappola has participated in a CME presentation sponsored by an educational grant from Abbott Laboratories and has served on a data monitoring board for BioSante Pharmaceuticals Inc.

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