Intervention
Testosterone Replacement Therapy (TRT)
Last updated Sun May 17 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
What it is
Replacement of endogenous testosterone in men with clinically and biochemically confirmed hypogonadism. Routes: intramuscular cypionate or enanthate, subcutaneous pellets, transdermal gels, oral undecanoate, nasal.
Why it’s of interest
Total testosterone declines roughly 1–2% per year after age 30 in many men. Symptomatic hypogonadism (low libido, fatigue, depressed mood, low muscle mass, low bone density) plus low total testosterone (commonly <300 ng/dL) is the canonical indication.
What TRT does well
- Improves libido, erectile function, energy in men with true hypogonadism.
- Increases lean mass and reduces fat mass (modest with TRT alone; larger with TRT + resistance training).
- Improves bone density.
- Improves haemoglobin (sometimes too much — see below).
Safety
- Erythrocytosis (raised haematocrit) — monitor and donate blood if needed.
- Cardiovascular: TRAVERSE (2023) found non-inferior major cardiovascular events vs placebo over ~3 years, somewhat reassuring; however, atrial fibrillation and pulmonary embolism rates were modestly higher.
- Prostate: TRT does not appear to cause prostate cancer but may accelerate growth of existing cancer; monitor PSA.
- Fertility: TRT suppresses spermatogenesis; preserve fertility first if family planning.
The off-label question
Use in men with "low-normal" testosterone or normal testosterone for performance or wellness purposes is not supported by long-term outcome data and carries the same risk profile.
Related entries
References
- Bhasin, S. et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 103, 1715–1744 (2018).
- Lincoff, A. M. et al. Cardiovascular safety of testosterone-replacement therapy (TRAVERSE). N. Engl. J. Med. 389, 107–117 (2023).