February 12, 2014
FDA Investigates Testosterone, CV Events After Second Study Shows Link

Washington, D.C.—With two separate studies suggesting increased risk of cardiovascular (CV) events among men using testosterone-replacement therapy, the FDA has announced that it is reassessing the safety of those products.

The FDA said it is investigating the risk of stroke, heart attack, and death in men taking FDA-approved products for low testosterone.

“We have been monitoring this risk and decided to reassess this safety issue based on the recent publication of two separate studies that each suggested an increased risk of cardiovascular events among groups of men prescribed testosterone therapy,” the agency reported in a safety alert.

In January, a study appearing in PLOS ONE, an online open access journal, found that the risk of myocardial infarction (MI) following initiation of testosterone therapy is substantially increased in older men and in younger men with pre-existing diagnosed heart disease.

The study, involving 55,593 men in a large healthcare database, compared the incidence rate of MI in the 90 days following the initial prescription with the rate in the one year prior to the initial prescription. Testosterone gel, testosterone micronized, testosterone cypionate, and testosterone transdermal system were the most common products used in the study cohort.

Post- and preprescription rates also were compared in a cohort of 167,279 men prescribed phosphodiesterase type 5 inhibitors (PDE5I)—sildenafil or tadalafil in this study. Study authors said they selected men receiving PDE5I prescriptions as a comparison group because some indications for prescription are similar to those for testosterone (TT) prescription and “because PDE5I is commonly prescribed to older men, does not have androgenic effects, and is not metabolized to other sex steroid hormones, such as dihydrotestosterone or estrogens.”

Researchers found that the post/preprescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81) for participants overall. In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I.

Study results showed that the RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged 75 years or older, although no trend was seen for PDE5I. In men younger than 65, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, according to the authors.

Another study late last year found that testosterone-replacement therapy increased risks of death, heart attack, or ischemic stroke in veterans who had undergone coronary angiography and had a low serum testosterone levels.

The Veterans Administration (VA)-funded study, published in November in the Journal of the American Medical Association, evaluated the association between the use of testosterone therapy and all-cause mortality, myocardial infarction and stroke among male veterans and whether underlying coronary artery disease modified this association.

The FDA said it would continue to evaluate information from the studies and other available data and then communicate final conclusions and recommendations.

Until then, it said, patients should not stop taking prescribed testosterone products without first discussing any questions or concerns with their healthcare professionals.

Clinicians, meanwhile, should consider whether the benefits of FDA-approved testosterone treatment is likely to exceed the potential risks of treatment and carefully following prescribing information on labels, the FDA added.

U.S. Pharmacist Social Connect