F tier · safety concern
Metribolone was abandoned in early clinical investigation because severe hepatic dysfunction appeared at very low exposures, was never marketed for human use in any country, and exists in the literature almost exclusively as a radiolabelled reference ligand for androgen receptor binding assays.
metribolone
Metribolone is a 17alpha-methylated 19-nortestosterone trienone that was investigated briefly around 1970 for advanced breast cancer and abandoned; the literature describes severe hepatic dysfunction arising at very low exposures. Its enduring scientific role is as the standard high-affinity 'hot ligand' R1881 in androgen receptor binding and photoaffinity labelling assays, not as a therapeutic agent.
the explanation
Metribolone, known in laboratories as R1881, is a research chemical used to measure how strongly other substances stick to the androgen receptor. It was tested briefly in people decades ago, caused serious liver problems at very small exposures, and was never sold as a medicine anywhere.
regulatory status
US Schedule III controlled substance; never marketed for human use anywhere; no approved medical indication has ever existed
Enumerated at 21 CFR 1308.13(f)(62) as 'methyltrienolone (17alpha-methyl-17beta-hydroxyestra-4,9,11-trien-3-one)'. It was investigated briefly for advanced breast cancer in the late 1960s to early 1970s and development was abandoned; it has never held a marketing authorisation in any jurisdiction. It is not a 'prohormone' that was later scheduled — it entered the controlled list as a recognised anabolic steroid, and it is legitimately supplied as a laboratory reagent and analytical reference ligand. Anabolic steroids as a class are Class C under the UK Misuse of Drugs Act 1971; prohibited at all times in sport under WADA.
how it works · proposed mechanism
Metribolone is an exceptionally high-affinity, metabolically inert androgen receptor agonist selected by pharmacologists precisely for those properties.
Reference 'hot ligand' for AR
Tritiated metribolone (R1881) has been the standard high-affinity radioligand in cellular androgen receptor binding assays and photoaffinity labelling since the mid-1970s. Its utility rests on tight, slowly dissociating binding that resists displacement and metabolic degradation in assay conditions.
Triene ring blocks metabolism
The 4,9,11-triene 19-nor skeleton prevents both aromatisation and 5alpha-reduction, and the C17alpha methyl blocks 17beta-hydroxyl oxidation. The molecule therefore persists essentially unmetabolised, which amplifies both receptor signalling and hepatic exposure.
Promiscuous nuclear receptor binding
Beyond the androgen receptor, metribolone binds the progesterone and glucocorticoid receptors with high affinity and acts as a potent antimineralocorticoid with mineralocorticoid receptor affinity comparable to aldosterone and spironolactone. This off-target promiscuity is a documented confounder in assays and a plausible contributor to systemic toxicity.
what’s reported
evidence shape
5 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
Metribolone's extreme potency figures come from castrated rodent bioassays and receptor binding work, not from any human trial that was ever completed, so its 'strength' is a laboratory measurement rather than a clinical one. The one thing the human record does document is that hepatic dysfunction appeared at very low exposures, which is why no marketing authorisation was ever sought.
key published findings
- Rodent bioassay (secondary pharmacology compendia): in castrated male rats metribolone showed roughly 120-300 times the oral anabolic potency and 60-70 times the androgenic potency of methyltestosterone; no equivalent human potency data exist.
- In vitro (Bonne and Raynaud, Steroids 1975): methyltrienolone was characterised as a specific high-affinity ligand for cellular androgen receptors, establishing its role as the reference radioligand still used in AR binding assays.
- Human clinical history: brief investigation for advanced breast cancer around 1970 was abandoned after severe hepatic dysfunction was observed at very low exposures; no completed controlled trial data were published.
- In vitro cross-reactivity: metribolone binds the progesterone and glucocorticoid receptors with high affinity and behaves as a potent antimineralocorticoid, with mineralocorticoid receptor affinity described as comparable to aldosterone and spironolactone.
- Regulatory (21 CFR 1308.13(f)(62)): methyltrienolone is a listed Schedule III anabolic steroid despite never having had any approved human indication.
limitations of the evidence
- There is effectively no modern human pharmacology literature; half-life, bioavailability and clearance are unknown and reported as null.
- Potency claims derive from rodent castration bioassays and receptor binding constants that do not translate reliably to human dose-response.
- The historical hepatotoxicity account comes from abandoned early clinical investigation summarised in secondary sources rather than from a published, indexed trial report.
documented safety signals
- Extreme hepatotoxicity is the defining documented signal: severe hepatic dysfunction was reported at very low exposures during early clinical investigation, and this is the stated reason human development was terminated.
- C17alpha alkylation places metribolone in the structural class LiverTox identifies as most closely associated with cholestatic liver injury, peliosis hepatis, hepatic adenoma and hepatocellular carcinoma.
- Metabolic inertness means there is no meaningful clearance pathway to limit hepatic exposure, so toxicity accumulates rather than self-limiting as with metabolically labile androgens.
- Off-target glucocorticoid and progesterone receptor agonism introduces the potential for adrenal-axis and reproductive-axis disruption independent of androgenic effects.
- Potent antimineralocorticoid activity implies potential for electrolyte and blood pressure disturbance not typical of other androgens.
- Profound HPG-axis suppression is expected from a non-aromatisable, high-affinity AR agonist: suppressed LH/FSH, arrested endogenous testosterone production, testicular atrophy and impaired spermatogenesis.
- Severe adverse lipid effects: 17alpha-alkylated, non-aromatisable androgens produce marked HDL cholesterol suppression with no oestrogenic counterbalance.
- Virilisation in women would be expected to be rapid and irreversible given the compound's androgenic potency in animal assay; no safe human exposure has ever been established.
- Because no pharmaceutical-grade human product has ever existed, all non-laboratory material is by definition of unverified origin, identity and purity.
identity
| full name | Metribolone / methyltrienolone (17beta-hydroxy-17alpha-methylestra-4,9,11-trien-3-one) |
| category | Anabolic & Androgenic |
| modality | steroid |
| formula | C19H24O2 |
| molar mass | 284.4 g/mol |
| cas | 965-93-5 |
laboratory handling
| storage | Laboratory reference material; store desiccated and protected from light, typically at -20 C for solids and radiolabelled preparations. Handle as a potent controlled reagent under appropriate containment. |
| solubility | Practically insoluble in water; soluble in ethanol, DMSO and dimethylformamide. Stock solutions for binding assays are conventionally prepared in ethanol or DMSO. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedElectronic Code of Federal Regulations (DEA) · 2026 · official
NCATS Inxight Drugs, US National Center for Advancing Translational Sciences · 2026 · official
PubChem, US National Library of Medicine · 2026 · official
NIDDK / NCBI Bookshelf · 2020 · review
Steroids · 1975 · preclinical
others in Anabolic & Androgenic