F tier · safety concern
Never an approved medicine, sold for years as an over-the-counter 'prohormone' supplement, and the only substantial human literature it generated is a body of case reports and case series documenting severe cholestatic liver injury, several with concurrent renal failure.
methasterone
Methasterone is a 17alpha-alkylated dihydrotestosterone derivative that was never developed as a prescription medicine but was sold from 2005 as the active ingredient of the over-the-counter supplement Superdrol before being placed in Schedule III. The peer-reviewed human record consists almost entirely of hepatotoxicity case reports and case series describing profound cholestatic jaundice, in some instances accompanied by acute kidney injury.
the explanation
Methasterone was sold in shops as a muscle-building supplement under the name Superdrol, despite never being tested or approved as a medicine. Doctors published a series of cases in which previously healthy young men developed severe jaundice and liver injury after taking it, and it is now a controlled substance.
regulatory status
US Schedule III controlled substance; no approved medical indication, ever; formerly sold as an OTC 'prohormone' dietary supplement and subsequently scheduled
Methasterone was never a commercially available prescription drug. It appeared in 2005 as a designer steroid marketed as the principal ingredient of the over-the-counter supplement Superdrol and was sold as a dietary supplement until the DEA classified it, with prostanozol, as a Schedule III anabolic steroid by final rule in 2012. The 2014 Designer Anabolic Steroid Control Act restated it statutorily, and DEA's 2023 implementing rule notes that methasterone and prostanozol were already listed under alternative chemical names; it now appears at 21 CFR 1308.13(f)(48) as 'methasterone (2alpha,17alpha-dimethyl-5alpha-androstan-17beta-ol-3-one)'. Anabolic steroids as a class are Class C under the UK Misuse of Drugs Act 1971. Added to the WADA prohibited list in 2009.
how it works · proposed mechanism
Methasterone is an orally active, non-aromatisable androgen receptor agonist whose oral durability comes at a direct hepatic cost.
C17alpha methyl drives cholestasis
Methylation at C17alpha blocks hepatic oxidation of the 17beta-hydroxyl and forces the liver to handle a metabolically resistant androgen on first pass. LiverTox identifies this exact modification as the principal structural driver of cholestatic injury across oral androgens.
2alpha methyl blocks reduction
The 2alpha methyl group sterically impedes reduction of the 3-keto function, increasing metabolic stability and receptor residence. Combined with the 5alpha-saturated A-ring, this yields a persistent, non-aromatisable androgenic signal.
Canalicular transport disruption
Biopsy findings in reported cases describe canalicular and hepatocellular cholestasis with pigmented macrophages, consistent with impaired bile acid and bilirubin export rather than hepatocellular necrosis. This explains the characteristic pattern of extreme hyperbilirubinaemia with only modest aminotransferase rise.
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
Because methasterone was sold as a dietary supplement rather than a drug, the users who supplied its entire human evidence base did so by presenting to hepatology units with jaundice, not by enrolling in trials. Nothing about its human pharmacokinetics, dose-response or long-term risk was ever characterised before or after it reached the market.
key published findings
- Human case series (Shah NL et al., Clin Gastroenterol Hepatol 2008;6:255-258): five previously healthy patients developed jaundice roughly two weeks after stopping methasteron, presented to tertiary centres two weeks later, and bilirubin continued to peak for a further 2-3 weeks before all cases resolved fully within 12 weeks of presentation without residual liver dysfunction.
- Human case report (Nasr J, Ahmad J, Dig Dis Sci 2009;54:1144-1146): severe cholestasis accompanied by renal failure following use of the designer steroid Superdrol/Methasteron, published with a literature review of related androgenic-steroid injury.
- Human review (LiverTox 2020): the bland cholestatic pattern typical of C17alpha-alkylated androgens presents with bilirubin often above 20 mg/dL against only modest enzyme elevation, latency of 1-4 months, and recovery that remains prolonged after withdrawal.
- Structure-activity (secondary compendia): methasterone is reported at roughly 400% the anabolic and 20% the androgenic activity of methyltestosterone in rodent assay, a high nominal anabolic-androgenic ratio with no corresponding human validation.
- Regulatory (DEA final rule 2012; 21 CFR 1308.13(f)(48)): methasterone moved from open OTC supplement sale to Schedule III control, with the classification restated by the Designer Anabolic Steroid Control Act of 2014.
limitations of the evidence
- The entire human evidence base is uncontrolled case reports and small case series, which cannot establish incidence, dose-response, or the proportion of exposed users who are affected.
- Supplement-era exposures were frequently to multi-ingredient products of unverified composition, so attribution to methasterone alone is imperfect in some reports.
- No human pharmacokinetic data exist; half-life, bioavailability and clearance are reported as null because no clinical development programme was ever conducted.
documented safety signals
- Severe cholestatic liver injury is the defining documented hazard: profound jaundice with bilirubin frequently exceeding 20 mg/dL, disproportionate to modest ALT/AST elevation, with biopsy showing canalicular and hepatocellular cholestasis.
- Delayed onset and delayed peak: in the published five-case series jaundice began approximately two weeks after the product was stopped and bilirubin continued rising for a further 2-3 weeks after presentation, meaning discontinuation does not immediately halt deterioration.
- Prolonged course: full biochemical resolution took up to 12 weeks from presentation in the reported series; cholestasis from this drug class is characteristically slow to reverse.
- Concurrent renal injury: published cases document acute renal failure alongside cholestasis, and a separate report describes cholestatic jaundice with IgA nephropathy attributed to the same OTC product.
- Peliosis hepatis and hepatic adenoma/hepatocellular carcinoma are established risks of prolonged C17alpha-alkylated androgen exposure, with tumour latency typically 5-15 years.
- Marked HDL cholesterol suppression: 17alpha-alkylated androgens induce hepatic triglyceride lipase and depress HDL, producing an atherogenic lipid profile; non-aromatisable DHT derivatives offer no oestrogenic offset.
- HPG-axis suppression with reduced LH/FSH, suppressed endogenous testosterone, testicular atrophy and impaired spermatogenesis.
- Virilisation in women, including irreversible voice deepening, hirsutism and clitoral enlargement; premature epiphyseal closure if exposure occurs before skeletal maturity.
- Supplement-market specific hazard: products were sold without dose verification, purity control, or adverse-event reporting infrastructure, and often combined methasterone with other undeclared steroids.
identity
| full name | Methasterone / methyldrostanolone (2alpha,17alpha-dimethyl-17beta-hydroxy-5alpha-androstan-3-one) |
| category | Anabolic & Androgenic |
| modality | steroid |
| formula | C21H34O2 |
| molar mass | 318.5 g/mol |
| cas | 3381-88-2 |
laboratory handling
| storage | Solid; store tightly closed, protected from light and moisture at controlled room temperature; certified reference solutions are supplied and stored refrigerated or frozen in acetonitrile. |
| solubility | Practically insoluble in water; soluble in ethanol, methanol, acetonitrile and DMSO. Analytical standards are commonly distributed as acetonitrile solutions. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedFederal Register (DEA) · 2012 · official
Federal Register (DEA) · 2023 · official
NIDDK / NCBI Bookshelf · 2020 · review
International Journal of Molecular Sciences · 2016 · review
Clinical Gastroenterology and Hepatology · 2008 · observational
Digestive Diseases and Sciences · 2009 · observational
others in Anabolic & Androgenic