A randomized, controlled clinical trial, recently published in The New England Journal of Medicine (NEJM), evaluated the cardiovascular safety of testosterone replacement therapy in middle-aged and older men with hypogonadism. The study included 5,246 men aged 45 to 80 years with high-risk or pre-existing cardiovascular disease, symptoms of hypogonadism, and low testosterone levels. Participants were randomly assigned to receive either a transdermal testosterone gel or a placebo gel. The primary endpoint was the occurrence of cardiovascular events such as death from cardiovascular causes, myocardial infarction, or stroke. A secondary endpoint also included coronary revascularization. The study sought to demonstrate non-inferiority by establishing an upper risk threshold for testosterone compared to placebo.
The study showed that testosterone replacement therapy was non-inferior to placebo in terms of major adverse cardiovascular events. The rate of primary cardiovascular events was similar between the testosterone and placebo groups. Sensitivity analyses also supported these findings. However, a higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism was observed in the testosterone group.
In conclusion, in middle-aged and older men with hypogonadism and pre-existing cardiovascular disease or at high risk of cardiovascular disease, testosterone replacement therapy was not associated with an increased risk of major adverse cardiovascular events compared with placebo. However, potential additional adverse effects, such as atrial fibrillation and renal and pulmonary complications, should be considered.