Testosterone therapy (TT) may increase the risk of MI considerably in older men and younger men with heart disease, according to a study published online Jan. 29 in PLOS One. The study found the risk in younger men with a history of heart disease to be more than doubled after starting treatment.

Researchers from Consolidated Research in Los Angeles, the University of California, Los Angeles and the National Cancer Institute in Bethesda, Md., used aggregated patient data from Truven Health Analytics and conducted a cohort study of 55,593 men who started TT. There were 48,539 younger than 65 and 7,054 who were 65 and older. They compared the number of MIs that occurred in the 90 days after the initial TT prescription (post-prescription rate) with the number of MIs that occurred in the year before the initial TT prescription (pre-prescription rate).

They also compared the MI incidence rates during the same time intervals in a group of men prescribed phosphodiesterase type 5 inhibitors (PDE5I, which were sildenafil [Viagra, Pfizer] or tadalafil [Cialis, Eli Lilly]), and then compared those rates to the TT post-prescription and pre-prescription rates. The outcome was a diagnosis of acute MI.

For all participants, the post- and pre-prescription rate ratio (RR) for TT was 1.36. Among the older age group, the risk was twofold after starting therapy—the RR was 2.19 for TT prescription and 1.15 for PDE5I. The ratio of rate ratios (RRR) comparing TT prescription to PDE5I was 1.9. The RR for TT prescription increased with age from 0.95 for men younger than 55 to 3.43 for men 75 and older. There was no such trend among the PDE5I group.

Among younger men, MI risk was only higher if there was a prior history of heart disease—RRs were 2.9 for TT prescription and 1.4 for PDE5I. The RRR was 2.07.

Exogenous testosterone, the authors explained, may cause physiologic changes that increase the risk of clotting and thrombotic disorders.

“Given the rapidly increasing use of TT, the current results, along with other recent findings emphasize the urgency of the previous call for clinical trials adequately powered to assess the range of benefits and risks suggested for each therapy,” the authors argued. Until then, they continued, clinicians should consider discussing cardiovascular risks with patients before starting this type of therapy.