Testosterone
Testosterone, the principal androgen
Written by Aaron CuhaReviewed Sep 2026
Also known as: TRT, Testosterone replacement therapy, Androgen replacement
The best-evidenced hormone on this site. A 5,246-man randomised trial settled the cardiovascular question, and 36 randomised trials in 8,480 women cover the half of the population nobody talks about.
Overview
Testosterone has better human evidence than almost anything else documented here, and it is also the compound most surrounded by noise, so this page leads with what the large randomised trials actually found.
On safety in men, the question is answered. TRAVERSE randomised 5,246 men aged 45 to 80 with existing or high-risk cardiovascular disease and genuinely low testosterone, and found no excess of cardiovascular death, heart attack or stroke against placebo. That was the fear that shadowed this treatment for a decade.
On benefit, the answer is specific rather than sweeping. In the T-Trials, testosterone reliably improved sexual activity, desire and erectile function. It did not improve vitality. Walking distance improved only when all three trial cohorts were pooled. Mood and depressive symptoms improved slightly. That is a real but narrower set of effects than the marketing implies.
For women, the evidence is better than the silence around it suggests, and it points at one indication rather than at general use. See below.
Mechanism of action
A 19-carbon steroid synthesised from cholesterol, mainly in the Leydig cells of the testis under luteinising hormone control, and in smaller amounts by the ovary and adrenal in women. It acts directly on the androgen receptor, a nuclear receptor that binds DNA and alters transcription. Two conversions matter clinically: 5-alpha-reductase converts it to dihydrotestosterone, a more potent androgen responsible for much of the effect on scalp hair and prostate, and aromatase converts it to oestradiol, which is responsible for much of its effect on bone, mood and libido in men. Exogenous testosterone suppresses luteinising hormone and follicle-stimulating hormone through negative feedback, which is why it reduces sperm production and testicular size.
Human evidence
Among the strongest evidence bases on this site: a 5,246-person cardiovascular safety trial, a coordinated set of randomised trials in older men, and 36 randomised trials in women pooled into one meta-analysis.
- TRAVERSE, 5,246 men: no excess cardiovascular death, heart attack or stroke against placebo, hazard ratio 0.96 (0.78 to 1.17).
- T-Trials: sexual activity, desire and erectile function improved significantly.
- T-Trials: vitality did not improve. Walking distance improved only in the pooled analysis, not in the trial designed to test it.
- 36 randomised trials in 8,480 women: significant improvement across every sexual function domain measured in postmenopausal women.
- In those same women, LDL cholesterol rose while total cholesterol, HDL and triglycerides fell, which is why route and formulation matter.
- Exogenous testosterone suppresses luteinising hormone and follicle-stimulating hormone, reducing sperm production. This matters enormously to anyone who may want children and is routinely underexplained at the point of prescription.
What this does not tell you: TRAVERSE tested a transdermal gel titrated to a defined range in men with genuinely low levels and high cardiovascular risk. It does not license supraphysiological dosing, and it does not speak to men whose testosterone is normal. The T-Trials answer is narrower than the marketing: sexual function improved, vitality did not, and physical function improved only on pooling. In women, the evidence supports one indication and the route matters. None of this is a case for testosterone in a man with a normal level and fatigue, which is the most common reason people seek it.
Reading the research record
Two things are worth saying plainly about this drug, and they point in opposite directions.
The first is that the scare was overdone. For a decade, testosterone carried a cardiovascular cloud built on observational data and a small trial stopped early. TRAVERSE was the properly powered answer, 5,246 men at high cardiovascular risk, and it came back clean. People who avoided treatment they needed on the strength of that cloud were badly served.
The second is that the benefit is narrower than the clinics selling it suggest. In the best randomised trials, sexual function improved and vitality did not, which is notable because fatigue is the single most common reason men ask for it. A man with a normal testosterone level and low energy has not been shown to benefit, and the trials enrolled men with levels below 300 ng/dL measured twice, fasting, in the morning. That diagnostic care is the part usually skipped.
For women, the gap is different and is a genuine failure of the system rather than of the evidence. There are 36 randomised trials and a position statement endorsed by eleven societies, and in most countries no approved product, which leaves women being prescribed a fraction of a male product with no label to guide it.
The evidence, charted
Fig. 1 · evidence composition
2of 5 citations (40%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 4 distinct years, 2016 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Approved
AU
Approved
CA
Approved
Approved in all four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2023
Cardiovascular safety of testosterone-replacement therapy
TRAVERSE. 5,246 men aged 45 to 80 with preexisting or high risk of cardiovascular disease, symptoms of hypogonadism and two fasting testosterone levels below 300 ng/dL, randomised double-blind to transdermal testosterone gel titrated to 350 to 750 ng/dL or placebo. Mean treatment 21.7 months, mean follow-up 33.0 months. Primary composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke occurred in 182 (7.0%) on testosterone and 190 (7.3%) on placebo, hazard ratio 0.96 (95% CI 0.78 to 1.17), p < 0.001 for non-inferiority.
New England Journal of Medicine - Human2016
Effects of testosterone treatment in older men
The T-Trials. Treatment raised testosterone into the mid-normal range for men aged 19 to 40. Sexual activity, sexual desire and erectile function all improved significantly. Vitality did not improve on the fatigue scale. The proportion improving 6-minute walking distance by at least 50 m did not differ in the Physical Function Trial but did when all three trials were pooled, 20.5% against 12.6%, p = 0.003. Mood and depressive symptoms were slightly better. Adverse event rates were similar.
New England Journal of Medicine - Review2019
Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data
36 randomised controlled trials, 8,480 participants. In postmenopausal women testosterone significantly improved satisfactory sexual event frequency (mean difference 0.85, 95% CI 0.52 to 1.18), sexual desire (SMD 0.36), pleasure, arousal, orgasm, responsiveness and self-image, and reduced sexual concerns and distress. Lipids moved: LDL cholesterol rose while total cholesterol, HDL cholesterol and triglycerides fell.
Lancet Diabetes and Endocrinology - Review2019
Global consensus position statement on the use of testosterone therapy for women
A consensus statement endorsed by eleven bodies including the International Menopause Society, The Endocrine Society, The North American Menopause Society and the Royal College of Obstetricians and Gynaecologists. The reference document for what testosterone therapy in women is and is not supported for.
Journal of Clinical Endocrinology and Metabolism - Review2026
Individualizing injectable testosterone replacement therapy in primary care: pharmacokinetics, symptom stability, safety monitoring, and injection interval
States that the interval between injections is sometimes chosen out of habit rather than clinical reasoning, that short-acting esters produce meaningful swings in serum exposure across the cycle especially at larger doses and longer intervals, and that every-two-week dosing should not be the automatic default. Where symptom cycling persists, the issue may be dose timing and peak-to-trough variation rather than an inadequate weekly total.
Cureus
Frequently asked questions
Does testosterone cause heart attacks?
The properly powered trial says no. TRAVERSE randomised 5,246 men with existing or high-risk cardiovascular disease and found 7.0% against 7.3% on the composite of cardiovascular death, heart attack and stroke, a hazard ratio of 0.96. That was the question hanging over this drug for a decade and it has been answered for replacement dosing in men who are genuinely low.
Will it fix my fatigue?
Probably not, and this is the most useful thing on the page. In the T-Trials, sexual activity, desire and erectile function improved significantly and vitality did not improve at all on the fatigue scale. Fatigue is the most common reason men ask for testosterone and it is the endpoint the trials failed to move.
What about testosterone for women?
Better supported than most people realise, and for one thing. A meta-analysis of 36 randomised trials in 8,480 participants found significant improvement in sexual desire, arousal, orgasm, pleasure and satisfying sexual events in postmenopausal women, with reduced distress. LDL rose while HDL and triglycerides fell, so route and formulation matter. A position statement endorsed by eleven medical societies sets out the boundaries, and in most countries there is still no approved female product.
Will it make me infertile?
It suppresses sperm production, and that is not a side effect but the expected consequence of the mechanism: exogenous testosterone shuts down luteinising and follicle-stimulating hormone through negative feedback. It is usually reversible on stopping and not always, and it is the fact most often underexplained at the point of prescription. If children are a possibility, raise it before the first injection rather than after.
Is one injection a week the right schedule?
It is often reasonable and it should not be automatic. Cypionate and enanthate are short-acting esters, so a large dose at a long interval produces high levels early and low levels late. The ester pages on this site cover the pharmacokinetics and what splitting the same weekly total does to that curve.