Testosterone replacement therapy (TRT)

TRT has genuine randomised human evidence, which puts it well ahead of most longevity clinic offerings, but the evidence supports narrower claims than the marketing does. TRAVERSE (n=5,246 men aged 45 to 80 with hypogonadal symptoms, testosterone under 300 ng/dL, and existing or high cardiovascular risk; NEJM 2023) found daily 1.62% testosterone gel non-inferior to placebo for major adverse cardiac events (7.0% vs 7.3%; HR 0.96, 95% CI 0.78 to 1.17). That is a safety result, not a benefit result: TRAVERSE showed TRT does not appear to raise MACE risk in that population, while also recording small excesses of atrial fibrillation, pulmonary embolism and fracture. The Australian T4DM trial (Wittert et al., Lancet Diabetes & Endocrinology 2021; n=1,007 men aged 50 to 74 with impaired glucose tolerance or new type 2 diabetes and testosterone at or below 14.0 nmol/L, explicitly WITHOUT pathological hypogonadism) found that two years of testosterone undecanoate added to a lifestyle programme cut two-year type 2 diabetes incidence by roughly 40%, with fat loss and strength gains. Notably, T4DM's own lead investigator cautioned that testosterone is not a substitute for lifestyle intervention, and follow-up reporting indicates the diabetes-prevention effect was not durable once treatment stopped. What the evidence does NOT show: no trial has demonstrated that TRT extends lifespan, reduces all-cause mortality, slows biological ageing, or improves any validated healthspan endpoint. There is no RCT evidence supporting testosterone in men with normal testosterone levels, and the long-term effects of decades-long supraphysiological or "optimisation" dosing outside diagnosed deficiency are untested. Fertility suppression is a real and sometimes irreversible consequence. The honest grade is: strong clinical evidence for symptom and metabolic outcomes in confirmed deficiency, no evidence for the longevity claim itself.

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