SAN DIEGO (FRONTLINE MEDICAL NEWS) – Testosterone therapy for men with low serum testosterone had no impact one way or another on cardiovascular risk in a large, community-based study.

“Testosterone therapy is not associated with any deleterious or beneficial effect on cardiovascular outcomes. But our study does reinforce that it’s very important to go back to the basics and try to manage the traditional risk factors that are known predictors of adverse outcomes,” Dr. Zuber Ali said at the annual meeting of the American College of Cardiology.

The cardiovascular impact of testosterone therapy in men with low serum levels is a controversial subject. Early studies reported cardioprotective benefits; however, at least three more recent studies found adverse effects, and the Food and Drug Administration recently issued a request that manufacturers of approved testosterone products revise their product labeling to include a new black box warning of “a possible increased cardiovascular risk associated with testosterone use.”

“Given these conflicting reports, we wanted to look at our experience in a large, community-based health care system,” explained Dr. Ali of the Aurora University of Wisconsin Medical Group in Milwaukee.

He presented a retrospective cohort study of 7,245 men, mean age 54 years, with a low baseline total testosterone level below 300 ng/dL who were followed during 2011-2014.

The combined rate of the composite outcome comprising all-cause mortality, acute MI, and stroke was 5.5% in men who received testosterone therapy, compared with 6.7% in those who did not. This translated into a statistically significant unadjusted 29% relative risk reduction in favor of testosterone therapy. However, upon adjusting for differences in baseline cardiovascular risk factors, the relative risk advantage for testosterone therapy dropped from 29% to 20%, which was no longer statistically significant.

This cardiovascular-neutral result was confirmed in a separate analysis in which 3,155 of the men on testosterone therapy were paired one to one with an equal number of controls who were propensity-matched on the basis of demographics and cardiovascular risk factors, including diabetes, atrial fibrillation, and chronic kidney disease. During a mean 1.8 years of follow-up, the composite outcome occurred in 1.7% of the testosterone therapy group and 2.2% of matched controls, a nonsignificant difference.

In a multivariate analysis, the significant predictors of cardiovascular outcomes proved to be dyslipidemia, age, length of follow-up, a history of acute MI or stroke/TIA, and smoking. Testosterone therapy didn’t make the list, according to Dr. Ali.

One audience member commented that while these data are reassuring up to a point, 1.8 years of follow-up is not very long from a cardiovascular risk perspective. Dr. Ali agreed, adding that he and his coinvestigators are continuing to follow these men and will be gathering longer-term data. But so far, at least, there is no signal of increased cardiovascular risk.

In issuing its request for a label change, the FDA also required manufacturers of approved testosterone products to conduct a well-designed clinical trial, either separately or in collaboration, to specifically address the question of possible cardiovascular risk. While Dr. Ali welcomed this development because it should finally provide definitive answers, he noted that no such study has begun, and long-term outcome data are years away. In the interim, he added, data such as he presented are probably the best that can be expected in terms of providing guidance on risks and benefits for physician/patient treatment decision making.

Dr. Ali reported having no financial conflicts regarding this study, which was conducted free of commercial support.


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