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Key Takeaway

The TRAVERSE trial changed the conversation around testosterone replacement therapy. For men with confirmed hypogonadism, TRT did not increase the risk of major cardiovascular events when testosterone levels were maintained within the normal physiological range. However, careful monitoring remains essential because some non-cardiovascular and non-major cardiovascular risks may still occur.

Why TRT Safety Has Been Controversial

For more than a decade, researchers debated whether testosterone therapy increased the risk of heart attacks, strokes, and cardiovascular death. Earlier studies produced conflicting results, creating uncertainty for both physicians and patients. The TRAVERSE trial was the first large, well-designed study capable of providing a more definitive answer.

What Is the TRAVERSE Trial?

TRAVERSE enrolled more than 5,000 men with confirmed low testosterone and elevated cardiovascular risk. Participants received either testosterone gel or placebo and were followed for more than three years. Researchers evaluated major adverse cardiovascular events (MACE), including heart attack, stroke, and cardiovascular death.

CALL OUT: Main Finding

TRT was not associated with a higher risk of major cardiovascular events compared with placebo when prescribed appropriately and monitored carefully.

Beyond Heart Attacks and Strokes

Although major cardiovascular outcomes were reassuring, researchers observed several safety signals that deserve attention. These included erythrocytosis (elevated hematocrit), atrial fibrillation, venous thromboembolism, pulmonary embolism, and acute kidney injury.

Erythrocytosis: The Most Consistent Side Effect

Among all adverse effects, elevated hematocrit was the most consistently reported. Higher hematocrit levels may increase blood viscosity and potentially raise thrombotic risk. Regular blood testing remains one of the most important aspects of TRT monitoring.

Atrial Fibrillation and Blood Clots

The study found slightly higher rates of atrial fibrillation and venous thromboembolism among testosterone users, although these differences were not statistically significant. Patients with a history of arrhythmias or clotting disorders should discuss risks carefully with their healthcare provider before starting therapy.

Blood Pressure and Kidney Health

A small increase in blood pressure was observed in some men receiving TRT. Acute kidney injury was also reported more frequently in the testosterone group, highlighting the importance of ongoing monitoring in men with pre-existing kidney disease or cardiovascular risk factors.

Organic vs Functional Hypogonadism

A critical message from modern guidelines is the distinction between organic and functional hypogonadism. Organic hypogonadism results from permanent dysfunction of the testes or pituitary gland and usually requires TRT. Functional hypogonadism is often driven by obesity, metabolic syndrome, diabetes, sleep apnea, or chronic illness and may improve when the underlying condition is treated.

Weight Loss Can Restore Testosterone

Lifestyle changes, diet, exercise, weight loss and sleep can improve testosterone levels in many men with obesity-related hypogonadism. In some cases, testosterone levels normalize without the need for long-term TRT.

Who Benefits Most from TRT?

Men with documented testosterone deficiency, persistent symptoms, and confirmed organic hypogonadism remain the best candidates for treatment. Benefits may include improved sexual function, energy, body composition, muscle mass, and quality of life.

Practical Monitoring Checklist

Before starting TRT, clinicians should evaluate hematocrit, PSA, blood pressure, cardiovascular risk factors, kidney function, sleep apnea risk, and fertility goals. Follow-up testing is typically recommended within 3–6 months and periodically thereafter.

Final Thoughts

Current evidence suggests that testosterone replacement therapy can be used safely in appropriately selected men with confirmed hypogonadism. The TRAVERSE trial provides strong reassurance regarding major cardiovascular events, but successful treatment still depends on proper diagnosis, individualized risk assessment, and ongoing monitoring.

REFERENCE:

Testosterone replacement therapy and cardiovascular safety in older men: lessons from TRAVERSE and beyond

Journal of Endocrinological Investigation

June 27, 2026

Daniele Tienforti et al.