The TRAVERSE trial, a recent investigation into the safety and efficacy of testosterone replacement therapy (TRT) in men with heightened cardiovascular risk factors, has garnered significant attention. Conducted with 5204 male participants aged 45 to 80, the trial focused on individuals exhibiting low total testosterone levels and signs of pre-existing cardiovascular disease (CVD) or increased risk. The primary aim of TRT is to address symptoms associated with low testosterone, ranging from changes in body composition to improved muscle mass, bone density, sexual function, mood, energy, and overall quality of life.
The trial outcomes indicated that TRT was noninferior to placebo concerning major adverse cardiac events (MACE). Specifically, there was no statistically significant difference in the incidence of MACE between the TRT group and the placebo group. However, it’s noteworthy that several side effects were observed in the TRT group, including a higher occurrence of atrial fibrillation, acute kidney injury, and pulmonary embolism. These findings raise questions about the cardiovascular impact of TRT at clinically relevant levels, given the relatively modest increase in total testosterone observed during the trial.
One crucial aspect highlighted by the trial is the necessity for a nuanced understanding of the cardiovascular effects of TRT, especially when applied to populations with heightened cardiovascular risk. The increase in median serum total testosterone levels in the intervention group was measured at 148 ng/dL, reflecting a relatively small elevation. Concerns arise about the cardiovascular implications of TRT at different levels, as the trial did not delve into potential effects with higher testosterone increases.
Despite the insights gained from the TRAVERSE trial, it’s imperative to acknowledge its limitations. Participant dropout rates were notably high in both the TRT and placebo groups throughout the study duration, surpassing 60%. While the trial anticipated high dropout rates and was designed accordingly, the potential introduction of an informative censoring bias poses challenges. This bias may occur when patients withdraw for reasons related to the study, potentially leading to an underrepresentation of primary outcomes in the TRT group.
Moreover, the trial’s methodology and participant selection might introduce biases. The availability of various FDA-approved and readily accessible TRT formulations raises questions about why individuals with low testosterone would willingly enroll in a trial with a 50% chance of receiving a placebo, especially with an expected duration of up to five years. Possible explanations include concerns about cardiovascular outcomes, possibly influenced by family history or a high level of risk aversion, potentially introducing a selection bias that could impact the generalizability of the cardiovascular safety results to the broader low-testosterone population.
In the broader context of testosterone replacement therapy, the article underscores the need for a careful consideration of risks and benefits. While the TRAVERSE trial contributes valuable insights, particularly in the context of cardiovascular safety, it prompts healthcare professionals to approach TRT prescriptions with caution, especially in populations with higher cardiovascular risk factors. The observed side effects and the relatively modest increase in total testosterone emphasize the importance of monitoring known cardiovascular risk factors during TRT, urging a comprehensive evaluation of hematocrit, lipid levels, blood pressure, and serum testosterone, particularly in the initial year of treatment. This nuanced approach aligns with the ongoing discourse around the potential long-term safety and efficacy of TRT in men with elevated cardiovascular risk.
