In short
Testosterone replacement therapy (TRT) is prescription treatment with testosterone, indicated for men with clinically diagnosed hypogonadism — consistently low testosterone levels on repeated blood tests combined with associated symptoms.
Diagnosis requires more than a single low lab value: professional guidelines (including from the Endocrine Society) call for at least two separate morning total testosterone measurements below the reference range, combined with consistent symptoms such as low libido, fatigue, or loss of muscle mass, before a hypogonadism diagnosis and TRT are appropriate. TRT is available as injections, transdermal gels or patches, pellets, and oral formulations, each with different dosing and side-effect profiles.
Long-standing safety concerns centered on cardiovascular risk and prostate cancer. The TRAVERSE trial, a large randomized controlled trial published in the New England Journal of Medicine in 2023 specifically designed to answer the cardiovascular safety question in men with hypogonadism and elevated cardiovascular risk, found that TRT was not associated with a higher rate of major adverse cardiac events compared to placebo over roughly two years of follow-up — an important, reassuring result, though the trial also found a higher incidence of atrial fibrillation, pulmonary embolism, and acute kidney injury in the testosterone group.
TRAVERSE evaluated TRT for its approved indication — diagnosed hypogonadism with symptoms — not as a longevity or anti-aging intervention in men with normal-for-age testosterone levels, which is a distinct off-label use some longevity clinics offer. Prescribing testosterone to a man without a confirmed hypogonadism diagnosis, purely to raise levels toward a younger reference range, has a materially thinner evidence base than the treatment of diagnosed low testosterone, and carries known risks including reduced fertility and testicular atrophy from suppressing the body's own production.
Worth remembering
- Requires two low morning testosterone readings plus symptoms for a hypogonadism diagnosis.
- TRAVERSE (2023, NEJM) found no increased major cardiac event rate but did find higher atrial fibrillation and blood clot rates.
- Off-label use in men without diagnosed hypogonadism has a much thinner evidence base.