Study Feeds Concerns About MI Risk With Testosterone Tx

Filling a prescription for testosterone therapy was associated with a greater risk of having a nonfatal myocardial infarction (MI) in the next 3 months, a large observational study showed.

The risk after a prescription was filled was more than doubled in men 65 and older overall compared with that in the year before the prescription (rate ratio 2.19, 95% CI 1.27-3.77), according to Robert Hoover, MD, ScD, of the National Cancer Institute in Bethesda, Md., and colleagues.

For younger men, testosterone therapy was associated with a greater risk only among those with pre-existing heart disease (RR 2.90, 95% CI 1.49-5.62), the researchers reported online in PLOS One.

"Given the rapidly increasing use of testosterone therapy, 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 such therapy," they wrote.

"Until that time, clinicians might be well advised to include serious cardiovascular events in their discussions with patients of potential risks, particularly for men with existing cardiovascular disease."

A potential cardiovascular risk tied to testosterone therapy -- which is becoming more popular, particularly among younger men -- drew attention based on the results of multiple studies released in recent years. In 2010, a small randomized trial showed that older men treated with testosterone therapy improved their strength and mobility, but at the cost of a greater cardiovascular risk.

A meta-analysis of smaller studies yielded a similar result, and the point was driven home last year by a study showing that male veterans who were undergoing coronary angiography had an elevated risk of all-cause death, MI, and ischemic stroke associated with the use of testosterone therapy.

But those prior studies did not have enough patients to explore the relationship in men with and without pre-existing heart disease and did not include very many younger men.

Both issues were addressed in the current study, which included 55,593 men who filled a first prescription for testosterone therapy and were included in a large healthcare claims database. The researchers compared the rate of acute MI in the 90 days after the prescription to that in the year before the prescription was filled.

In the overall cohort, the risk of nonfatal MI was higher by 36% in the post-prescription period (4.75 versus 3.48 acute MIs per 1,000 persons per year; RR 1.36, 95% CI 1.03-1.81). The risk tended to increase with age (P=0.03 for trend).

For men 65 and older, the greater risk of MI seen in the 90 days after a prescription was filled was no longer apparent from 91 to 180 days among those who did not have a refill.

"Since we censored follow-up at the first refill, and the supply for most prescriptions was 30 to 90 days, it is likely that there was little use of the medication in the 91 to 180 day post-prescription interval when the risk declined," the authors noted. "Thus, the pattern of change in risk by supply of testosterone is consistent with an effect of the drug, and underscores the concerns raised by three recent studies in predominantly older men."

A drug effect also was supported by the lack of an association between filling a prescription for a phosphodiesterase type 5 inhibitor and risk of an acute MI.

In addition, there are plausible biological mechanisms to explain the relationship with testosterone therapy.

"Exogenous testosterone is associated with physiologic changes that predispose to clotting and thrombotic disorders, including increased blood pressure, polycythemia, reductions in HDL cholesterol, and hyperviscosity of the blood and platelet aggregation," the authors wrote. "Testosterone therapy also increases circulating estrogens, which may play a role in the observed excess of adverse cardiovascular-related events, given that estrogen therapy has been associated with this excess in both men and women."

The study was limited, however, by the observational design, the use of administrative data that lacked information on indications for treatment, and the inclusion of nonfatal MIs only.

Source: www.medpagetoday.com