More has been settled about testosterone in the last three years than in the previous ninety. A contemporary review of what the recent landmark trials mean for clinical practice in older men is the best single synthesis of that position.[1]
Here is the ledger.
Settled
Cardiovascular safety, in the studied population. TRAVERSE randomised 5,204 men aged 45–80 with hypogonadism and cardiovascular disease or increased risk, and found testosterone non-inferior to placebo for major adverse cardiac events.[2]
The labelling. The FDA issued class-wide labeling changes for testosterone products in February 2025,[3] and requested a further round in June 2026 that removed the age-related hypogonadism limitation of use February 2025 had kept.[7] See what the 2025 label change did. The randomised evidence has since been pooled again across 41 trials and 11,161 men, with no significant increase in cardiac or prostate cancer events.
Several benefit questions — answered in the negative. No cognitive improvement.[4] No erectile improvement, though sexual activity and desire did improve.[5] Mood improvement real and small, with no benefit in strictly defined persistent depressive disorder and no effect on sleep or cognition.[6]
Newly complicated
Fractures. Clinical fractures in 3.50% on testosterone versus 2.46% on placebo, hazard ratio 1.43.[7] A safety signal from the same trial that delivered the cardiovascular reassurance — and the finding most often reported backwards.
Unchanged
The diagnostic standard. Symptoms plus unequivocally, consistently low concentrations, confirmed on a repeat fasting morning measurement.[8]
The target. Mid-normal.[8]
The monitoring plan and contraindications.[8]
Erythrocytosis as the most common side effect, with a hematocrit action threshold of 54%.[9]
Still open
Long-term data beyond trial duration. TRAVERSE is the largest, not the longest.
Younger men. The evidence base skews middle-aged and older.
Comparative formulation and schedule data. No trial randomises the same weekly total across different delivery schedules — see daily vs weekly dosing.
Women. A global consensus statement exists;[10] the trial base behind it is a fraction of the male literature — see the research gap.
What it means for someone deciding
The cardiovascular objection is gone for men who meet the criteria. Nothing else about the decision changed: you still need a confirmed diagnosis, a cause investigation, contraindication screening and a monitoring plan — what good TRT actually looks like.
And expectations should follow the evidence, not the marketing. The things testosterone reliably does are narrower than commonly advertised, and knowing that in advance is what prevents a treatment working as predicted from feeling like a failure.
Frequently asked questions
Is TRT safe now? Non-inferior to placebo for major adverse cardiac events in the studied population.[2] The fracture finding is a real counterweight.[7]
Should more men be on it? The diagnostic criteria did not change.[8] TRAVERSE removed an objection; it did not widen eligibility.
What is the single best summary? The 2024 review of the landmark trials' clinical implications.[1]
Next in this series
From a rooster experiment to a metered spray — the whole arc in one place.
Continue with from roosters to spray bottles.
References
11 sources
- 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
- 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
- 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
- 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
- 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
- Agrawal P, Singh SM, Kohn T. Management of Erythrocytosis in Men Receiving Testosterone Therapy: Clinical Consultation Guide. Eur Urol Focus. 2023;9(1):20–21. doi:10.1016/j.euf.2022.10.008 · PMID 36335038
- Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019;104(10):4660–4666. doi:10.1210/jc.2019-01603 · PMID 31498871
- 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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