Increased Risk of Death with Testosterone Therapy

Men receiving testosterone therapy showed a 29% greater risk of death, heart attack, and stroke, according to a recent study that appears in The Journal of the American Medical Association. Topping more than 5 million in 2011, the number of annual prescriptions for testosterone supplements has climbed considerably in recent years, the study authors note. Given the increasing prevalence of testosterone therapy, the study highlights the importance of determining and discussing need vs. risk with patients. “Primary care providers should discuss the potential benefits and risks of testosterone therapy with their patients prior to initiating testosterone therapy, and they should make sure that patients who are currently taking testosterone therapy are actually benefiting from it,” says Anne Cappola, MD, ScM, author of an accompanying editorial. “There is substantial direct-to-consumer marketing of testosterone for ‘low T syndrome,’” says Cappola, associate professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism in the Perelman School of Medicine at the University of Pennsylvania. “There needs to be evidence of low morning testosterone levels on two occasions and symptoms of hypogonadism before initiating testosterone. Evidence from actual prescribing patterns suggests that this is not always the case.” The researchers reviewed nationwide data from more than 8,700 veterans with low levels of testosterone, comparing the 1,223 men who were taking testosterone therapy with the 7,489 men who were not. On average, the patients were in their early 60s—all had underwent cardiographic angiography and most had risk factors for heart disease, such as high blood pressure, diabetes, and unhealthy levels of cholesterol. Nearly 26% of the men using testosterone either died, had a heart attack, or suffered a stroke within 3 years of the heart test, compared with 20% of nonusers. There were not enough events to do subgroup analyses by age, health status, type of testosterone preparation, or degree of testosterone deficiency. “A strength of this study is that everyone had cardiac catheterization performed, so that it was known who had coronary artery disease and who did not,” Cappola says. “One interesting finding is that there was no difference in risk from testosterone use between those who had preexisting coronary artery disease and those who did not—both sets of patients were at increased risk.” Based on the findings, it’s unclear why testosterone therapy appears to increase the risk of these events. “Ideally, we would get the answer from clinical cardiovascular outcome data from a large randomized clinical trial,” Cappola says. “Such a trial is unlikely to be funded. Instead, we will have to piece together the benefit and risk data from the T Trial, which is looking at a number of surrogate outcomes and should be completed in 2015, and from other carefully conducted observational studies of men who are currently taking testosterone.” —Colleen Mullarkey References 1. Vigen R, O’Donnell CI, Baron AE, Grunwald GK, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in me with low testosterone levels. JAMA. 2013;310(17):1829-1836. doi:10.1001/jama.2013.280386. 2. Cappola AR. Testosterone therapy and risk of cardiovascular disease in men. [Editorial]. JAMA. 2013;310(17):1805-1806. doi:10.1001/jama.2013.280387