Abstract
This paper comments on a study that evaluates the risk of long-term cardiovascular events in men with hypogonadism undergoing testosterone replacement therapy. In a multicenter, randomized, double-blind, placebo-controlled noninferiority study, the authors included men aged 45 to 80 years who had a high risk of cardiovascular disease or had previously experienced it.
Patients reported symptoms of hypogonadism, which were laboratory confirmed (fasting serum testosterone levels were < 300 ng/dl (10.4 nmol/L) based on two reliable measurements). Randomization was conducted in a 1 : 1 ratio for daily use of transdermal 1.62% testosterone gel (n = 2 596) or matching placebo (n = 2 602).
The primary cardiovascular endpoint was the time from randomization to the first occurrence of any component of a major adverse cardiovascular event (MACE), which was defined as a combination of the following: (1) cardiovascular death, (2) non-fatal myocardial infarction, (3) non-fatal stroke. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo.
The primary cardiovascular endpoint occurred in 182 patients (7.0%) in the testosterone-treated group and in 190 patients (7.3%) in the placebo-treated group [HR 0.96; 95% confidence interval, 0.78-1.17; p < 0.001 for noninferiority). In men with hypogonadism and pre-existing or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of MACE, according to the analysis.