The cardiovascular effects of testosterone-replacement therapy (TRT) in middle-aged and older men with low testosterone, or hypogonadism, have been debated for years. Some studies suggest it increases cardiovascular risks, while others argue it might lower them. Smaller trials have been inconclusive, often underpowered and too brief to assess long-term outcomes.

The Trial Study

In response to these uncertainties, the FDA issued a directive in 2015 requiring testosterone manufacturers to conduct trials to determine if TRT raises cardiovascular risks and overall safety of TRT. This led to the TRAVERSE trial, aimed at clarifying TRT’s effects on heart health in men with hypogonadism, who also had preexisting or high cardiovascular risk.

The trial, conducted across 316 U.S. sites, was a rigorous double-blind, placebo-controlled study. It involved 5,246 men, aged 45 to 80, with either existing cardiovascular disease or multiple risk factors, such as hypertension or diabetes. To qualify, participants also needed documented low testosterone levels and symptoms like reduced libido or energy. Those with severe hypogonadism or conditions like prostate cancer were excluded.

Participants were randomly assigned to receive either a daily testosterone gel or a placebo gel. Both groups were monitored for major adverse cardiac events, including death from heart-related causes, nonfatal heart attacks, and strokes. The researchers also kept track of secondary outcomes like hospitalizations for heart failure or cases of venous thromboembolism.

The trial lasted an average of 33 months, with a large number of participants discontinuing their treatment (over 60% in both groups). Testosterone levels in the treatment group rose significantly, while the placebo group showed minimal changes. Despite this, the primary cardiovascular outcome showed no significant difference between the two groups. The hazard ratio for major cardiac events was 0.96, indicating TRT was not inferior to placebo.

However, some side effects raised concerns. The testosterone group had a higher incidence of pulmonary embolism, though the overall numbers were small. They also experienced more cases of nonfatal arrhythmias and atrial fibrillation. Blood pressure rose slightly in the testosterone group compared to the placebo group. Prostate cancer rates were similar between groups, but PSA levels increased more in the testosterone group.

What Was Found

The findings provide reassurance about the cardiovascular safety of TRT in men at high cardiovascular risk. However, the increased rates of certain side effects, like pulmonary embolism and arrhythmias, highlight the need for caution. Men considering TRT should discuss potential risks and benefits with their healthcare provider, especially if they have a history of cardiovascular or thrombotic events.

In conclusion, the TRAVERSE trial adds valuable data to the ongoing debate about testosterone therapy’s safety. While it does not significantly increase the risk of major heart problems, some adverse effects warrant further investigation and careful consideration in clinical practice. For men struggling with symptoms of low testosterone, TRT remains an option. The treatment is not without risks that need to be carefully managed.