The cardiovascular effects of testosterone replacement therapy (TRT) in middle-aged and older men with hypogonadism have been a topic of debate, with conflicting results from previous studies. Up until about 2010, it appeared that cardiovascular disease risk was typically reduced in those undergoing TRT. Then, some studies suggested an increased cardiovascular risk associated with TRT, while others found no such association. To address these concerns, the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial was conducted.
Design Overview
The TRAVERSE trial, a randomized, double-blind, placebo-controlled study, aimed to determine the effects of TRT on the incidence of major adverse cardiac events among middle-aged and older men with hypogonadism and either preexisting cardiovascular disease or a high risk of cardiovascular disease. The trial enrolled 5,246 patients and was conducted throughout the United States from May 2018 thru February 2022. It is important to note: Almost half of subjects in study were at least 65 years old, and more than half had existed cardiovascular disease.
Participants were randomly assigned to receive daily transdermal 1.62% testosterone gel or matching placebo gel for an average length of 22 months; just short of 2 years. The primary safety endpoint was the occurrence of major adverse cardiac events, including death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary cardiovascular endpoints included additional cardiac events, such as coronary revascularization.
Results
The results of the trial indicated that TRT was not statistically different from placebo with respect to occurrence of major adverse cardiac events. There were no significant differences in the incidence of primary safety endpoint events between the testosterone and placebo groups. Additionally, no clinically meaningful differences were observed in secondary cardiovascular endpoints between the two groups.
However, the incidence of pulmonary embolism was slightly higher in the testosterone group compared to the placebo group. Adverse events such as nonfatal arrhythmias, atrial fibrillation, and acute kidney injury were also more common in the testosterone group.
Despite these findings, TRT demonstrated beneficial effects on various outcomes such as sexual function, bone mineral density, anemia correction, and reduction of depressive symptoms in older men.
Therefore, the results of the TRAVERSE trial provide valuable insights into the cardiovascular safety of TRT and may help clinicians and patients make more informed decisions regarding its use in older men with hypogonadism and cardiovascular risk factors.
Considering the data above, TRT does not appear to significantly differ from placebo in terms of cardiovascular risk among middle-aged and older men with hypogonadism and either preexisting cardiovascular disease, or a high risk of cardiovascular disease. However, caution should be exercised, especially in patients with a history of thromboembolic events, as TRT may increase the risk of certain adverse events such as pulmonary embolism and arrhythmias.
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Citations: Lincoff, A. Michael, et al. “Cardiovascular safety of testosterone-replacement therapy.” New England Journal of Medicine, vol. 389, no. 2, 13 July 2023, pp. 107–117, https://doi.org/10.1056/nejmoa2215025.