Lessons learned from the TRAVERSE trial

As the largest testosterone therapy (TTh) clinical trial to be performed, the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial has been a significant milestone in testosterone (T) research, offering valuable insights into the safety and efficacy of TTh.1 The TRAVERSE trial was created in response to 2015 Food and Drug Administration guidance requiring manufacturers of approved T products to conduct a large cardiovascular (CV) clinical trial designed specifically to investigate whether TTh was associated with increased major adverse cardiovascular events (MACE). The TRAVERSE investigators added several additional planned studies to investigate the effects of TTh on prostate outcomes, sexual benefits, fractures, depression, unexplained anemia, and diabetes. In this report, we address the first 4 of these (Figure 1). The TRAVERSE trial was a randomized, double-blind, placebo-controlled trial conducted from May 2018 to January 2023. Inclusion criteria included serum T concentration <300 ng/dL on 2 occasions, symptoms of T deficiency, and being at high risk for CV events based on prior history of heart disease or the presence of multiple CV risk factors. Men were randomized to daily application of 1.62% T gel or placebo gel, with dose titration aimed to maintain T levels between 350 and 750 ng/dL and hematocrit <54%.