Testosterone and Cardiovascular Health: What the Latest Research Shows

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

The 2023 TRAVERSE trial — the largest RCT of TRT to date — found no increased cardiovascular risk with testosterone therapy in men with hypogonadism and pre-existing cardiovascular disease. Optimal testosterone levels (400-700 ng/dL) are associated with better cardiovascular outcomes than both low and supraphysiological levels.

The Cardiovascular Controversy in TRT

For over a decade, the cardiovascular safety of testosterone replacement therapy was one of the most contentious questions in endocrinology. Two observational studies published in 2013–2014 suggested increased cardiovascular risk with TRT, triggering an FDA safety review and a black box warning. Subsequent research has largely contradicted these findings, culminating in the landmark TRAVERSE trial published in 2023.

The TRAVERSE Trial: Definitive Evidence

The TRAVERSE trial was a randomized, double-blind, placebo-controlled trial involving 5,246 men aged 45–80 with hypogonadism and pre-existing cardiovascular disease or high cardiovascular risk. The primary finding: testosterone therapy did not increase the risk of major adverse cardiovascular events (MACE). The hazard ratio was 0.96 (95% CI 0.78–1.17), definitively establishing non-inferiority of TRT to placebo for cardiovascular safety.

Secondary Findings and Nuances

While the TRAVERSE trial was reassuring for overall cardiovascular safety, it did identify some secondary signals: testosterone therapy was associated with a higher rate of atrial fibrillation (3.5% vs 2.4%), a higher rate of acute kidney injury, and a higher rate of pulmonary embolism. These findings underscore the importance of individualized risk assessment and monitoring in TRT patients.

The U-Shaped Relationship

Epidemiological data consistently shows a U-shaped relationship between testosterone levels and cardiovascular risk: both very low testosterone (<200 ng/dL) and very high testosterone (>1,000 ng/dL) are associated with increased cardiovascular risk, while optimal levels (approximately 400–700 ng/dL) are associated with the best cardiovascular outcomes.

Hematocrit: The Real Cardiovascular Concern

The most significant cardiovascular risk associated with TRT is erythrocytosis — an increase in red blood cell mass and hematocrit. Elevated hematocrit increases blood viscosity and thrombotic risk. This is why hematocrit monitoring is essential in TRT patients, with most guidelines recommending dose reduction or phlebotomy if hematocrit exceeds 54%.