In the TRAVERSE trial, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events in men aged 45 to 80 years with hypogonadism and preexisting or a high risk of cardiovascular disease, researchers report. “Our findings regarding the cardiovascular safety of testosterone may facilitate a more informed consideration of the potential benefits and risks of testosterone therapy among middle-aged and older men with hypogonadism.”
The multicenter, randomized, double-blind, placebo-controlled, noninferiority trial included 5,246 men with preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng/dL. Randomized to daily transdermal 1.62% testosterone gel or placebo gel, the participants had these outcomes based on a primary cardiovascular safety endpoint of the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke: “The mean (± SD) duration of treatment was 21.7 ± 14.1 months, and the mean follow-up was 33.0 ± 12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P <0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group.”
Editorial: “This trial fills a major gap in knowledge concerning testosterone supplementation in older men with hypogonadism who are at high risk for cardiovascular events, and it provides critical safety information for patients and providers who are faced with making decisions about testosterone replacement,” writes an editorialist. “At least over a 2-year treatment period, testosterone-replacement therapy appeared to impart no additional risk of major adverse cardiac events. However, the safety of longer-term therapy, the implications of supplementation to reach higher testosterone levels, and the adverse effects that appeared to be associated with this therapy must be better understood.”