TRAVERSE enrolled 5,204 men aged 45 to 80 with hypogonadism and either existing cardiovascular disease or increased cardiovascular risk, randomised them to testosterone or placebo, and measured major adverse cardiac events. Testosterone was non-inferior to placebo.[1]
That is the study the 2010 signal demanded, and it took thirteen years to arrive.
Why the design settles what the earlier evidence could not
Three features do the work.
It was built for the question. Not a function trial reporting cardiac events as adverse events; not a database of prescriptions. Major adverse cardiac events were the point.
It enrolled the highest-risk population. Every participant had cardiovascular disease or increased cardiovascular risk.[1] If testosterone raised cardiac risk, this is the population in which it would show — and enrolling them is what makes a reassuring result meaningful rather than merely underpowered.
It was randomised and placebo-controlled. Which removes the confounding that makes observational data about testosterone prescribing so difficult to interpret.
The sub-studies matter as much as the headline
TRAVERSE was a platform, and the nested studies answered questions the cardiovascular result does not touch. Several of them are less flattering:
Fractures. Clinical fractures occurred in 3.50% of men on testosterone versus 2.46% on placebo — hazard ratio 1.43.[2] More fractures on treatment, not fewer. This is the single most misreported TRAVERSE finding.
Sexual function. Testosterone improved sexual activity, hypogonadal symptoms and sexual desire — but not erectile function.[3]
Mood. Modest improvements in mood and energy, with no significant benefit in men meeting strict criteria for persistent depressive disorder, and no effect on cognition or sleep quality.[4]
A trial that had simply been a marketing exercise would not have produced that set of results.
What it did not do
It did not test every population. The participants were middle-aged and older men with hypogonadism and cardiovascular risk. It says nothing about young men, or men with normal testosterone.
It did not test every formulation. The sexual function sub-study used 1.62% testosterone gel.[3]
It did not make testosterone protective. Non-inferiority is the finding.[1]
What changed as a result
The FDA issued class-wide labeling changes for testosterone products in February 2025.[5] That is the regulatory system catching up to a 2023 result — and public perception still lags both.
Details of what the finding means in practice are in what TRAVERSE means for TRT today, and the full main-trial explainer is in the TRAVERSE trial.
Frequently asked questions
Does TRAVERSE prove TRT is heart-safe? It found testosterone non-inferior to placebo for major adverse cardiac events in men with hypogonadism and cardiovascular disease or risk.[1] That is a strong result within its population and design.
Does it apply to me? If you are outside the enrolled population — younger, or without cardiovascular risk — the trial's direct applicability is limited, though the direction is reassuring.
What about the fracture finding? Real and important: 3.50% versus 2.46%, HR 1.43.[2] It belongs in any monitoring conversation, particularly for older men — see starting TRT after 50.
Next in this series
A definitive answer to one question raises the next: what does it actually change for someone deciding today?
Continue with what TRAVERSE means for TRT today.
References
5 sources
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107–117. doi:10.1056/NEJMoa2215025 · PMID 37326322
- Snyder PJ, Bauer DC, Ellenberg SS, et al. Testosterone Treatment and Fractures in Men with Hypogonadism. N Engl J Med. 2024;390(3):203–211. doi:10.1056/NEJMoa2308836 · PMID 38231621
- Pencina KM, Travison TG, Cunningham GR, et al. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. J Clin Endocrinol Metab. 2024;109(2):569–580. doi:10.1210/clinem/dgad484 · PMID 37589949
- Bhasin S, Seidman S, Travison TG, et al. Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy. J Clin Endocrinol Metab. 2024;109(7):1814–1826. doi:10.1210/clinem/dgae026 · PMID 38205962
- U.S. Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products. February 28, 2025. fda.gov
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