The TRAVERSE study investigated the cardiovascular safety of testosterone replacement therapy (TRT) in men with hypogonadism. Its primary objective was to determine if testosterone therapy increased the risk of major adverse cardiovascular events (MACE) compared to a placebo. This research aimed to clarify a debated topic within the medical community.
Why the TRAVERSE Study Was Conducted
Before the TRAVERSE study, uncertainty surrounded the cardiovascular safety of testosterone replacement therapy. Earlier observational studies yielded conflicting results, with some suggesting increased cardiovascular risk. This led the FDA to issue a warning in 2015, restricting TRT indications.
These previous studies often had limitations, such as their observational design, making it difficult to establish cause-and-effect relationships. A knowledge gap existed regarding TRT’s long-term cardiovascular impact due to the lack of robust, randomized, placebo-controlled trials. Therefore, a large, well-designed study was needed to provide evidence on the cardiovascular safety of testosterone therapy in men with documented low testosterone levels and existing cardiovascular risk or disease.
Core Findings of the TRAVERSE Study
The TRAVERSE study was a large, randomized, placebo-controlled trial involving over 5,200 men aged 45 to 80, all of whom had low testosterone levels and either pre-existing cardiovascular disease or a high risk for it. Participants received either a daily transdermal 1.62% testosterone gel or a placebo gel, with doses adjusted to maintain testosterone levels within a target range of 350 to 750 ng/dL. The average follow-up period for participants was approximately 22 to 33 months.
The primary outcome focused on major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal heart attack, or non-fatal stroke. The study found no significant increase in MACE in the testosterone group compared to the placebo group. The number of recorded events was comparable, with 7% in both groups, indicating similar cardiovascular safety.
While the overall cardiovascular safety endpoint was met, the study identified some other adverse events with a slightly higher incidence in the testosterone group. These included atrial fibrillation (3.5% vs. 2.4%), acute kidney injury (2.3% vs. 1.5%), and pulmonary embolism (0.9% vs. 0.5%). The study also found no increased risk of prostate cancer or worsening of lower urinary tract symptoms.
Implications for Testosterone Therapy
The TRAVERSE study’s findings offer reassurance regarding the cardiovascular safety of testosterone replacement therapy when used appropriately in men with confirmed hypogonadism. The results suggest that for middle-aged and older men with low testosterone and cardiovascular risk, TRT does not increase the risk of major adverse cardiovascular events over the typical duration of treatment. This clarity is meaningful given previous uncertainties and conflicting data.
The study’s outcomes have already begun to influence clinical guidelines and physician prescribing practices. The FDA, for instance, has removed language from the Black Box warning related to increased cardiovascular risk for testosterone products and now requires the inclusion of TRAVERSE results in product labeling. This change allows for more informed discussions between physicians and patients about the potential benefits and risks of TRT. However, the study’s findings apply specifically to men with documented hypogonadism and do not endorse the widespread use of testosterone in men without a clear indication.
For patients considering TRT, the TRAVERSE study provides a more balanced perspective on its safety profile. While the overall cardiovascular risk was not elevated, the increased incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone group warrants careful consideration. Physicians may need to exercise caution when prescribing testosterone to individuals with a history of thromboembolic events or arrhythmias. These detailed findings allow for more personalized risk-benefit assessments, helping patients and their healthcare providers make informed decisions about testosterone therapy.