One question closed. The rest of the framework stands, and one new caution was added. TRAVERSE found testosterone non-inferior to placebo for major adverse cardiac events in 5,204 men with hypogonadism and cardiovascular disease or increased risk,[1] and the FDA issued class-wide labeling changes for testosterone products in February 2025.[2]
Here is the honest accounting of what that does and does not change.
What changed
The cardiovascular objection is resolved for this population. A man with cardiovascular risk who meets the diagnostic criteria is no longer facing an unquantified cardiac question.
The labelling changed — twice. February 2025, class-wide.[2] Then in June 2026 the FDA requested further updates, removing the age-related hypogonadism limitation of use that February 2025 had explicitly retained, and revising the prostate cancer and benign prostatic hyperplasia information.[7] Both steps are set out in what the 2025 label change did.
A fracture signal appeared. This is new information against treatment, from the same trial: clinical fractures in 3.50% on testosterone versus 2.46% on placebo, hazard ratio 1.43.[3] It is the most frequently reversed finding in the whole TRAVERSE literature, and it belongs in monitoring conversations for older men — see starting TRT after 50.
What did not change
The diagnostic standard. Symptoms plus unequivocally, consistently low concentrations, confirmed by repeating a fasting morning measurement.[4] TRAVERSE enrolled men with two testosterone concentrations below 300 ng/dL plus hypogonadal symptoms[5] — it did not loosen the entry criteria, it applied them.
The target. Mid-normal.[4]
The monitoring plan. Symptoms, adverse effects, compliance, serum testosterone, hematocrit, and prostate cancer risk in the first year.[4] See the 3-month panel.
The contraindications. Including fertility plans, elevated hematocrit, untreated severe sleep apnea and recent myocardial infarction or stroke.[4]
What testosterone does and doesn't improve. No erectile improvement,[5] no cognitive benefit,[6] mood improvement real but small.[7]
What it does not license
Treating men with normal testosterone. The trial enrolled men with two concentrations below 300 ng/dL and symptoms.[5] It says nothing about men who do not meet that definition.
Skipping the workup. The guideline still recommends establishing the cause of a confirmed deficiency.[4]
Marketing testosterone as cardioprotective. Non-inferiority is not benefit.[1]
Where the evidence still thins out
A contemporary review of the landmark trials' clinical implications is the best single summary of the current position.[8] Several gaps persist: long-term data beyond trial duration, younger populations, and comparative data between formulations and dosing schedules — the last of which is set out in daily vs weekly dosing.
Frequently asked questions
Is TRT safe now? For major adverse cardiac events in the population studied, TRAVERSE found non-inferiority to placebo.[1] "Safe" as a blanket term overstates any trial result — the fracture finding is a live counterexample.[3]
Should I start TRT because TRAVERSE was reassuring? Only if you meet the diagnostic criteria. The trial did not change who should be treated.[4]
Why does my doctor still seem cautious? Possibly appropriate caution about the fracture finding, contraindications, or your specific situation — all still current.
Has the FDA warning been removed? The FDA issued class-wide labeling changes in February 2025, and requested a further round in June 2026.[2][7] Your prescriber works from the current label.
Where the story goes next
Cardiovascular risk was never testosterone's only contested territory. Metabolism, women's physiology, male contraception and the state of modern practice are the remaining seasons, in progress.
In the meantime: what higher doses buy you and testosterone therapy for women.
References
9 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
- U.S. Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products. February 28, 2025. fda.gov
- 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
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364
- 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
- Resnick SM, Matsumoto AM, Stephens-Shields AJ, et al. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. JAMA. 2017;317(7):717–727. doi:10.1001/jama.2016.21044 · PMID 28241356
- 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
- Grossmann M, Anawalt BD, Yeap BB. Testosterone therapy in older men: clinical implications of recent landmark trials. Eur J Endocrinol. 2024;191(1):R22–R31. doi:10.1093/ejendo/lvae071 · PMID 38917356
- U.S. Food and Drug Administration. Testosterone Information — postmarket drug safety information for patients and providers, including the TRAVERSE results and the June 2026 requested prescribing-information updates. fda.gov
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