TRT and the TRAVERSE Trial: What the Cardiovascular Data Means

Written by Adam Maggio | Medically reviewed by Dr. Mitchell Ross, MD, ABAARM

The TRAVERSE trial demonstrated that testosterone replacement therapy (TRT) does not increase the risk of major adverse cardiovascular events in men with hypogonadism and existing cardiovascular disease or high risk. However, it did identify increased incidences of atrial fibrillation, acute kidney injury, and pulmonary embolism, underscoring the need for careful patient selection and monitoring.

TRT and the TRAVERSE Trial: Understanding Cardiovascular Safety

When considering testosterone replacement therapy (TRT), a primary concern for many patients and clinicians is its impact on cardiovascular health. The TRAVERSE trial, a landmark study published in the New England Journal of Medicine in June 2023, provides crucial insights into this very question. It's the most definitive answer we're likely to get regarding TRT's cardiovascular safety in a specific patient population.

The TRAVERSE trial was a large, multicenter, randomized, double-blind, placebo-controlled, noninferiority study involving over 5,200 men aged 45 to 80 years. These participants all had documented symptomatic hypogonadism, defined by two fasting morning testosterone levels below 300 ng/dL, and either pre-existing cardiovascular disease or a high risk for it. Unlike many smaller studies that lacked the power or duration to assess cardiovascular outcomes adequately, TRAVERSE was specifically designed to address the FDA's mandate for clearer data on TRT's cardiovascular effects.

Key Findings: Cardiovascular Events

The primary endpoint of the TRAVERSE trial was a composite of major adverse cardiovascular events (MACE), including cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. Over a mean follow-up period of 33 months, the results were reassuring: MACE occurred in 7.0% of men in the testosterone group compared to 7.3% in the placebo group. This yielded a hazard ratio of 0.96 (95% confidence interval, 0.78-1.17), demonstrating that TRT was noninferior to placebo regarding MACE. This means that for men with hypogonadism and cardiovascular risk, TRT did not increase their risk of these serious cardiovascular events.

Important Nuances and Adverse Events

While the overall cardiovascular safety profile was favorable, the TRAVERSE trial did highlight some important nuances and specific adverse events. A higher incidence of certain conditions was observed in the testosterone group:

• Atrial fibrillation: 3.5% with testosterone vs. 2.4% with placebo
• Acute kidney injury: 2.3% with testosterone vs. 1.5% with placebo
• Pulmonary embolism: 0.9% with testosterone vs. 0.5% with placebo

These findings are critical. While the increased risk of pulmonary embolism aligns with some previous observations, the elevated rates of atrial fibrillation and acute kidney injury were novel. This doesn't mean TRT is unsafe, but it underscores the importance of careful patient selection and ongoing monitoring. For instance, men with a history of thromboembolic events should be approached with caution when considering TRT.

Who Benefits from These Findings?

It's crucial to understand that the TRAVERSE trial's findings apply specifically to the population studied: middle-aged and older men with documented symptomatic hypogonadism and existing cardiovascular disease or high cardiovascular risk. This isn't a blanket endorsement for all men. The results don't apply to individuals without low testosterone levels, those taking super-physiological doses, or men receiving TRT from 'low T centers' without proper diagnosis and monitoring. In those settings, the careful titration of testosterone doses to maintain levels between 350-750 ng/dL and hematocrit below 54%—as was done in TRAVERSE—is often absent.

Practical Takeaway

For men with symptomatic hypogonadism and cardiovascular concerns, the TRAVERSE trial offers significant reassurance regarding the cardiovascular safety of TRT when used appropriately. However, it's not a therapy without risks. You'll need to have your testosterone levels carefully monitored, and your doctor will watch for potential side effects like atrial fibrillation, acute kidney injury, and pulmonary embolism. Always discuss your full medical history with your physician to determine if TRT is the right choice for you, ensuring it's prescribed and managed within established clinical guidelines.