Safety of Testosterone-Replacement Therapy in Older Men

This editorial reviews the cardiovascular safety of testosterone-replacement therapy in older men, contextualized by results from the TRAVERSE trial. The randomized, placebo-controlled study evaluated transdermal testosterone in 5246 men aged 45–80 with symptoms of hypogonadism and elevated cardiovascular risk. Over a median of 22 months, testosterone therapy was noninferior to placebo for the composite outcome of death from cardiovascular causes, nonfatal MI, or nonfatal stroke (HR 0.96; CI 0.78–1.17). However, testosterone-treated men experienced slightly higher rates of pulmonary embolism (0.9% vs. 0.5%), atrial fibrillation (3.5% vs. 2.4%), arrhythmias (5.2% vs. 3.3%), and acute kidney injury (2.3% vs. 1.5%). The editorial raises concerns about generalizability due to participants’ high prevalence of obesity and diabetes, and notes the relatively short trial duration compared to the decades-long evolution of atherosclerosis. Estradiol levels increased modestly, with unclear implications. 

This editorial reviews the cardiovascular safety of testosterone-replacement therapy in older men, contextualized by results from the TRAVERSE trial. The randomized, placebo-controlled study evaluated transdermal testosterone in 5246 men aged 45–80 with symptoms of hypogonadism and elevated cardiovascular risk. Over a median of 22 months, testosterone therapy was noninferior to placebo for the composite outcome of death from cardiovascular causes, nonfatal MI, or nonfatal stroke (HR 0.96; CI 0.78–1.17). However, testosterone-treated men experienced slightly higher rates of pulmonary embolism (0.9% vs. 0.5%), atrial fibrillation (3.5% vs. 2.4%), arrhythmias (5.2% vs. 3.3%), and acute kidney injury (2.3% vs. 1.5%). The editorial raises concerns about generalizability due to participants’ high prevalence of obesity and diabetes, and notes the relatively short trial duration compared to the decades-long evolution of atherosclerosis. Estradiol levels increased modestly, with unclear implications.