S tier · elite
Testosterone is the only compound in this group that is an approved human medicine supported by both classical controlled efficacy trials and a modern, adequately powered randomised cardiovascular safety trial (TRAVERSE, 5,246 men randomised).
testosterone
Testosterone is the reference androgen and the only agent in this set with a regulator-approved human indication, namely replacement therapy in men with clinically and biochemically confirmed hypogonadism. Its evidence base spans randomised dose-response trials, a formal Endocrine Society guideline, and a large randomised cardiovascular safety trial, though that evidence describes treatment of a deficiency state rather than enhancement in men with normal androgen levels.
the explanation
Testosterone is the natural male hormone, and injectable versions are licensed medicines used when a man's body genuinely cannot make enough of it. It has been studied far more thoroughly than anything else on this list, but the studies were done in men with a diagnosed deficiency, not in healthy people looking for extra muscle.
regulatory status
Approved prescription medicine (US, EU, UK); DEA Schedule III controlled substance
Depo-Testosterone (testosterone cypionate) is FDA-approved for replacement therapy in males with primary hypogonadism or hypogonadotropic hypogonadism and is labelled Schedule III. Aveed (testosterone undecanoate, approved March 2014) carries a boxed warning for pulmonary oil microembolism and anaphylaxis and is dispensed only through a restricted REMS programme. Sustanon 250 is licensed in the UK for testosterone replacement in confirmed male hypogonadism and contains testosterone propionate 30 mg, phenylpropionate 60 mg, isocaproate 60 mg and decanoate 100 mg per ml (176 mg total testosterone per ml). Approved use is for diagnosed hypogonadism, not for athletic or cosmetic enhancement, and the substance is prohibited in sport.
how it works · proposed mechanism
Testosterone acts as a direct androgen-receptor agonist whose signal is tissue-selectively amplified or diverted by two enzymes, 5-alpha-reductase and aromatase.
Direct androgen receptor agonism
Testosterone binds the cytosolic androgen receptor, which dimerises and translocates to the nucleus to act on androgen response elements. In skeletal muscle this is associated with increased myofibrillar protein accretion and satellite-cell number in published human and animal work.
5-alpha-reduction and aromatisation
5-alpha-reductase converts testosterone to the more potent dihydrotestosterone in skin, scalp and prostate, while CYP19A1 aromatase converts it to oestradiol in adipose and other tissue. This dual conversion explains why androgenic skin and prostate effects and oestrogenic effects such as gynaecomastia can both arise from the same parent molecule.
Negative feedback on the HPG axis
Circulating testosterone and its oestradiol metabolite suppress hypothalamic GnRH pulsatility and pituitary LH and FSH secretion. Exogenous administration therefore reduces endogenous testicular testosterone production and spermatogenesis, which the FDA labelling records as oligospermia, testicular atrophy and subfertility at supratherapeutic exposure.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The strong evidence base describes correction of a diagnosed deficiency in men with hypogonadism, and TRAVERSE explicitly enrolled middle-aged and older men with hypogonadism plus established or high cardiovascular risk. It does not generalise to supraphysiologic use in eugonadal people, to unregulated product, or to the multi-agent regimens documented in observational cohorts of AAS users.
key published findings
- Human trial (randomised, Bhasin 1996, NEJM): 43 men received placebo or testosterone enanthate 600 mg weekly for 10 weeks with or without strength training; the testosterone-plus-exercise arm gained 6.1 ± 0.6 kg fat-free mass, with bench-press strength up 22 ± 2 kg and squat up 38 ± 4 kg, versus essentially no change on placebo without training.
- Human trial (randomised, TRAVERSE, NEJM 2023): among 5,246 randomised hypogonadal men with cardiovascular disease or high risk, major adverse cardiac events occurred in 7.0% on testosterone versus 7.3% on placebo (hazard ratio 0.96, 95% CI 0.78–1.17), meeting noninferiority over a mean follow-up of about 33 months.
- Human trial (randomised, TRAVERSE secondary safety): atrial fibrillation occurred in 3.5% versus 2.4%, acute kidney injury in 2.3% versus 1.5%, and pulmonary embolism in 0.9% versus 0.5%, testosterone versus placebo.
- Human meta-analysis (Calof 2005, 19 RCTs, 651 testosterone-treated and 433 placebo-treated men): haematocrit above 50% was roughly four times more likely on testosterone (OR 3.69, 95% CI 1.82–7.51), and combined prostate events were more frequent (OR 1.78, 95% CI 1.07–2.95).
- Regulatory (FDA labelling): testosterone undecanoate injection carries a boxed warning for serious pulmonary oil microembolism reactions and anaphylaxis that can follow any injection including the first, requiring 30 minutes of observation in a healthcare setting.
limitations of the evidence
- TRAVERSE studied a transdermal gel formulation in men with confirmed hypogonadism, so its reassuring cardiovascular result cannot be transferred wholesale to injectable esters or to supraphysiologic exposure.
- Bhasin 1996 was a 10-week trial in 43 men and was never designed or powered to detect cardiovascular, hepatic or psychiatric harm.
- Almost all high-quality trial data come from replacement dosing in deficiency states; randomised trials replicating the doses and durations reported in observational cohorts of non-medical users would not pass ethical review.
documented safety signals
- Polycythaemia and erythrocytosis: haematocrit above 50% roughly four times more likely than placebo in randomised trials (Calof 2005); FDA labelling requires periodic haemoglobin and haematocrit monitoring on long-term androgen therapy.
- Venous thromboembolism: postmarketing reports of deep vein thrombosis and pulmonary embolism appear in the Depo-Testosterone label; pulmonary embolism was numerically higher on testosterone in TRAVERSE (0.9% versus 0.5%).
- Pulmonary oil microembolism and anaphylaxis: boxed warning on testosterone undecanoate injection, presenting as cough urge, dyspnoea, throat tightening, chest pain, dizziness and syncope during or immediately after injection.
- Atrial fibrillation and acute kidney injury: both numerically increased on testosterone in TRAVERSE.
- HPG-axis suppression and infertility: dose-dependent suppression of LH and FSH, with the label recording testicular atrophy, oligospermia, subfertility and infertility at supratherapeutic exposure.
- Adverse lipid shift: serum cholesterol may rise on therapy per the label; observational data in AAS users show marked HDL reduction (Hartgens 2004: HDL-C fell from 1.08 to 0.43 mmol/l during self-administered AAS use).
- Hepatic: prolonged high-dose androgen use is associated in labelling with hepatic adenomas, hepatocellular carcinoma and peliosis hepatis.
- Blood pressure elevation, and oedema with or without congestive heart failure in people with pre-existing cardiac, renal or hepatic disease.
- Prostate: combined prostate events more frequent than placebo in meta-analysis; known or suspected prostate or breast carcinoma is a contraindication in the Sustanon SmPC.
- Virilisation in women and accelerated bone maturation in children, some changes irreversible if exposure continues.
- Injection-related infection risk applies to any intramuscular oil injection outside clinical settings: in 366 men injecting image- and performance-enhancing drugs, 42% ever reported redness, swelling and tenderness at an injection site and 6.8% ever had an abscess or open wound (Hope 2015).
- Long-term non-medical AAS exposure is associated with myocardial dysfunction and accelerated coronary atherosclerosis (Baggish 2017: LVEF 52 ± 11% in users versus 63 ± 8% in non-users).
identity
| full name | Testosterone (injectable esters and blends) |
| category | Anabolic & Androgenic |
| modality | steroid |
| formula | C19H28O2 |
| molar mass | 288.4 g/mol |
| cas | 58-22-0 |
| half-life | Ester-dependent. The Depo-Testosterone label states the half-life of testosterone cypionate given intramuscularly is approximately eight days; enanthate is reported at roughly 4.5 days, propionate substantially shorter, and undecanoate substantially longer. |
laboratory handling
| storage | Oil-based injectable esters are stored at controlled room temperature, typically 20–25 °C, protected from light in the original carton; refrigeration is not used and can cause crystallisation. Aqueous suspension formulations require resuspension before withdrawal. |
| solubility | The free steroid and its esters are practically insoluble in water. The Depo-Testosterone label describes testosterone cypionate as an oil-soluble ester, insoluble in water and freely soluble in alcohol, chloroform, dioxane and ether; commercial injectables are solutions in vegetable oils such as cottonseed, sesame, castor or arachis oil with benzyl alcohol and benzyl benzoate co-solvents. |
| co-studied with | Reference note only, not guidance: observational cohorts of non-medical users describe near-universal polypharmacy. The HAARLEM cohort of 100 male amateur athletes reported an average of 901 mg per week of AAS equivalents across multiple agents for a median 13 weeks, and only 47% of 272 seized or submitted product samples actually contained the labelled substance. This confounds attribution of any adverse outcome to a single molecule and means observational harm data describe regimens, not compounds. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedJournal of Clinical Endocrinology & Metabolism · 2018 · official
DailyMed / US FDA · 2025 · official
DailyMed / US FDA · 2025 · official
New England Journal of Medicine · 1996 · randomized
New England Journal of Medicine · 2023 · randomized
Journals of Gerontology Series A: Biological Sciences and Medical Sciences · 2005 · reviews
others in Anabolic & Androgenic