Key Findings on the Efficacy and Safety of Testosterone Therapy from Two Large Randomized Trials

Despite widespread use of testosterone therapy, its efficacy and safety in men with age-related low testosterone remain a matter of debate. Elucidating its benefits and risks is essential for clinical decision-making.

This narrative review synthesizes evidence from two large randomized controlled trials: the Testosterone Trials (T Trials) and the TRAVERSE trial. The T Trials assessed the efficacy of testosterone treatment in men ≥65 years with age-related syndromic androgen deficiency. The TRAVERSE trial assessed long-term cardiovascular safety of testosterone therapy in men aged 45-80 years with high cardiovascular risk. Prostate and skeletal safety were also assessed. We critically evaluate the design, outcomes, and shortcomings of these trials.

In the T Trials, testosterone therapy, compared with placebo, improved sexual function and mood, but not physical function, vitality, or cognitive function. In the TRAVERSE trial, testosterone therapy was noninferior to placebo with respect to major adverse cardiovascular events (MACE). Prostate-related events were comparable between groups, but fracture rates were unexpectedly higher in the testosterone group.

Results from the T Trials and TRAVERSE trial showed that testosterone therapy improves sexual function and mood but not vitality or physical function. Importantly, it did not increase MACE in men at high risk of cardiovascular disease. Based on these data, treatment with testosterone could be considered in middle-aged and older men with syndromic androgen deficiency to target symptoms where it has demonstrated efficacy, whereas therapies other than testosterone might be warranted for outcomes that were not improved by testosterone.