Study casts doubt on safety of testosterone therapy

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Testosterone therapy may increase the risk of death, MI or ischemic stroke, according to results from a Veterans Affairs study. Whether those findings apply to a broader population of men is unclear, an editorialist wrote, but “prescribers and patients should be wary.” The study and editorial were published Nov. 6 in JAMA.

Physicians ordered more than 5 million prescriptions for testosterone in 2011, but the effects on cardiovascular outcomes and mortality have yet to be established, wrote Rebecca Vigen, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues. Using a program that collects data from 76 catheterization laboratories, they identified 23,173 male veterans who underwent coronary angiography between 2005 and 2011 and had total testosterone levels checked.

Of those men, 8,709 had total testosterone levels below 300 ng/dL. The group had significant comorbidities, with 20 percent showing a prior history of MI, 50 percent with diabetes and more than 80 percent with coronary artery disease (CAD). Fourteen percent of those patients started testosterone therapy after angiography.

Compared with patients who did not initiate testosterone therapy, the testosterone therapy group had higher event rates at one year, two years and three years (absolute risk differences of 1.3 percent, 3.1 percent and 5.8 percent, respectively). Testosterone use was associated with a 29 percent increased risk of adverse outcomes, regardless of whether patients had CAD or not.

“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, LDL [low-density lipoprotein] levels, and use of secondary prevention medications,” they wrote. “These findings raise concerns about the potential safety of testosterone therapy.”

The researchers encouraged physicians to continue telling patients about the benefits of testosterone therapy but recommended they also point out that the long-term risks are not known and there potentially may be some harm from use.

The study was retrospective and observational, Vigen et al acknowledged, and results may be affected by unmeasured confounders and biases. The patient population also limited generalizability, a view that editorialist Anne R. Cappola, MD, shared.

Cappola, an associate editor at JAMA and an associate professor at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, wrote that the study included a real-world patient population of men whose comorbidities might exclude them from randomized clinical trials. Still, she questioned whether the results could be extrapolated to the broader population of men prescribed to testosterone for improving strength, sexual function or other enhancements.

She wrote that physicians should be wary when prescribing testosterone. “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.”