Testosterone and the heart:
what TRAVERSE found

The design

TRAVERSE randomized more than 5,200 men aged 45 to 80 with symptoms of low testosterone and two low morning levels. All had existing cardiovascular disease or a high risk of it. They received daily testosterone gel or placebo gel. The main question was whether testosterone was no worse than placebo for major adverse cardiovascular events: cardiovascular death, heart attack or stroke.

The main result

Testosterone was non-inferior to placebo. The primary outcome occurred in 182 men on testosterone and 190 on placebo, a hazard ratio of 0.96. The trial found no increase in heart attacks, strokes or cardiovascular deaths. It was built to show safety, not benefit, and it does not show that testosterone protects the heart.

What rose

Some adverse events were more common on testosterone. Atrial fibrillation occurred in 3.5% of men on testosterone versus 2.4% on placebo (91 versus 63 men, P = 0.02). Acute kidney injury and pulmonary embolism were also reported more often in the testosterone group. Our physicians review clotting history, heart rhythm and kidney function before treatment and follow them during it.

Fractures

A TRAVERSE fracture substudy, published in 2024, found the opposite of what many men hoped. Clinical fractures occurred in 91 men on testosterone (3.50%) and 64 on placebo (2.46%), a hazard ratio of 1.43 (95% CI 1.04 to 1.97) over a median of 3.19 years. Testosterone did not lower fracture risk. Most fractures followed falls or trauma, most often of the ribs, wrist and ankle. The authors suggested that more physical activity could explain part of the rise; that is a hypothesis, not a finding.

Prostate

TRAVERSE found no significant increase in prostate cancer or prostate-related events. That is reassuring, but it does not replace prostate checks. The 2018 Endocrine Society guideline calls for PSA monitoring during the first year of treatment, with urologic review if PSA rises above 4 ng/mL or increases by more than 1.4 ng/mL within 12 months.

Blood counts

Testosterone raises red blood cell production in many men. Hematocrit, the share of the blood made of red cells, is measured during treatment. If it climbs above the guideline threshold, therapy is paused, and it is restarted at a lower dose only after hypoxia and sleep apnea have been evaluated.

What this does not say

• TRAVERSE tested a daily testosterone gel in men with symptoms, confirmed low levels, and existing or high heart risk. It does not describe healthy men with normal levels, and it does not describe other formulations or doses.
• The trial used a brand-name product. Our products are compounded or generic versions and were not studied in TRAVERSE.
• Non-inferiority is a safety result, not a benefit. An average does not predict what happens to one man.
• The fracture and atrial fibrillation signals are reasons for careful selection and monitoring, not reasons to rule treatment out, and the trial does not settle the long-term question.

Sources

1. 1.Lincoff AM et al. Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). N Engl J Med 2023. NEJM
2. 2.Snyder PJ et al. Testosterone Treatment and Fractures in Men with Hypogonadism. N Engl J Med 2024;390:203-211. NEJM
3. 3.Bhasin S et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2018;103:1715-1744. JCEM
4. 4.Cunningham GR et al. Prostate-Specific Antigen Levels During Testosterone Treatment of Hypogonadal Older Men: Data from a Controlled Trial. J Clin Endocrinol Metab 2019;104:6238-6246. JCEM
5. 5.Snyder PJ et al. Effects of Testosterone Treatment in Older Men. N Engl J Med 2016;374:611-624. NEJM