C tier · mixed
A genuinely approved drug with a full FDA label and decades of oncology and endocrinology use, but the evidence base is old, largely pre-modern-trial, and paired with well-documented hepatic and androgenic toxicity that has driven it out of routine practice.
fluoxymesterone
Fluoxymesterone is a 17alpha-alkylated, non-aromatisable oral androgen that retains an approved US label for male hypogonadism, delayed puberty, and palliative treatment of androgen-responsive breast cancer in a narrow postmenopausal window. Its documented pharmacology is reasonably well characterised, but the label itself carries warnings for peliosis hepatis and hepatic tumours, and published human data are dominated by older reports rather than contemporary controlled trials.
the explanation
Fluoxymesterone is an old prescription male hormone pill that is still technically approved in the US for a few narrow uses. It is chemically modified to survive being swallowed, and that same modification is what makes it hard on the liver.
regulatory status
US Schedule III controlled substance; approved medical indication retained on label
Enumerated at 21 CFR 1308.13(f)(33) as 'fluoxymesterone (9-fluoro-17alpha-methyl-11beta,17beta-dihydroxyandrost-4-en-3-one)'. The Halotestin US prescribing information (Pharmacia and Upjohn, label version 2006) is marked CIII and lists approved indications for male hypogonadism, delayed puberty, and palliation of androgen-responsive recurrent mammary cancer in women more than one but less than five years postmenopausal; branded supply has become limited. Anabolic steroids as a class are Class C under the UK Misuse of Drugs Act 1971. Prohibited at all times in sport under the WADA anabolic agent category.
how it works · proposed mechanism
Fluoxymesterone is a direct androgen receptor agonist whose fluorination and 11beta-hydroxylation confer oral durability and block oestrogen conversion.
C17alpha methyl blocks clearance
Methylation at C17alpha sterically hinders hepatic oxidation of the 17beta-hydroxyl, the main first-pass route that destroys oral testosterone. This is the modification that makes the compound orally active and is also the structural feature most consistently linked to cholestatic liver injury across this drug class.
11beta-OH prevents aromatisation
The 11beta-hydroxyl group sterically obstructs the aromatase active site, so fluoxymesterone is reported to be non-aromatisable to an oestrogen. The consequence is an androgen signal unopposed by any oestrogenic counter-regulation of lipids or gonadotrophins.
Low SHBG binding, high free fraction
Fluoxymesterone binds human sex hormone-binding globulin with under 5% of testosterone's affinity, leaving most circulating drug unbound. A large free fraction means receptor occupancy is disproportionate to total serum concentration relative to native androgens.
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
The approved-drug status makes fluoxymesterone look better evidenced than it is: the label rests on mid-twentieth-century practice rather than modern randomised data, and the same document warns of hepatic adenoma, hepatocellular carcinoma and peliosis hepatis. Its high androgenicity also means virilising effects in women are described on-label as potentially irreversible.
key published findings
- Human regulatory (FDA label, DailyMed): approved for replacement therapy in primary and secondary male hypogonadism, delayed puberty in boys, and palliation of androgen-responsive recurrent breast cancer in women 1-5 years postmenopausal.
- Human PK (secondary pharmacology literature): reported oral bioavailability of approximately 80% and elimination half-life of approximately 9.2 h, described as long relative to testosterone.
- Human label safety: prolonged high-dose androgen therapy is associated with hepatic adenomas, hepatocellular carcinoma and peliosis hepatis, characterised on the label as all potentially life-threatening.
- In vitro binding: fluoxymesterone binds human SHBG with less than 5% the affinity of testosterone, and the C11beta hydroxyl sterically blocks aromatisation.
- Human review (LiverTox, 2020): across C17alpha-alkylated androgens, cholestasis occurs in roughly 1% of treated patients, with bilirubin frequently exceeding 20 mg/dL despite only modest aminotransferase elevation; one documented case reached 53 mg/dL.
limitations of the evidence
- The approved indications rest on clinical practice and case series predating modern randomised trial standards; no contemporary controlled efficacy or safety trials define its risk-benefit.
- Published pharmacokinetic parameters (bioavailability, half-life) derive largely from secondary pharmacology compendia rather than accessible primary PK studies.
- Hepatic and lipid toxicity data for this specific molecule are extrapolated substantially from class-level C17alpha-alkylated androgen literature rather than fluoxymesterone-specific cohorts.
documented safety signals
- Hepatotoxicity from C17alpha alkylation: bland cholestasis with disproportionate hyperbilirubinaemia (often >20 mg/dL) and comparatively modest ALT/AST rise; latency typically 1-4 months and recovery frequently prolonged after cessation (LiverTox).
- Peliosis hepatis: blood-filled hepatic sinusoids and cysts carrying a risk of rupture and intra-abdominal haemorrhage; explicitly warned on the Halotestin label as potentially life-threatening.
- Hepatic neoplasia: hepatocellular adenoma and hepatocellular carcinoma reported with prolonged androgen exposure, with typical latency of 5-15 years; some lesions regress after drug withdrawal.
- HDL suppression: 17alpha-alkylated androgens characteristically induce hepatic triglyceride lipase and lower HDL cholesterol, an atherogenic shift; the label additionally notes serum cholesterol may increase during androgen therapy.
- HPG-axis suppression: exogenous androgen suppresses LH and FSH, producing reduced endogenous testosterone production, testicular atrophy and impaired spermatogenesis, which may not fully recover.
- Virilisation in women: the label warns that deepening of the voice and clitoral enlargement may be irreversible and that therapy must be discontinued at the first sign of mild virilism to prevent irreversible change.
- Non-aromatisable androgen load without oestrogenic buffering may adversely affect bone and lipid regulation relative to aromatisable androgens.
- Additional class effects documented for androgens include sodium and fluid retention, polycythaemia, prostatic hypertrophy and androgenic alopecia; in prepubertal use, premature epiphyseal closure.
identity
| full name | Fluoxymesterone (9-fluoro-11beta,17beta-dihydroxy-17alpha-methylandrost-4-en-3-one) |
| category | Anabolic & Androgenic |
| modality | steroid |
| formula | C20H29FO3 |
| molar mass | 336.4 g/mol |
| cas | 76-43-7 |
| half-life | Approximately 9.2 h (elimination; secondary pharmacology literature) |
laboratory handling
| storage | Solid reference material; store tightly closed in a light-resistant container at controlled room temperature, or refrigerated/frozen for analytical standards. Protect from moisture. |
| solubility | Practically insoluble in water; soluble in ethanol, methanol and DMSO, as is typical for neutral C19/C20 steroids. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedDailyMed / US FDA (Pharmacia and Upjohn) · 2006 · official
Electronic Code of Federal Regulations (DEA) · 2026 · official
PubChem, US National Library of Medicine · 2026 · official
NIDDK / NCBI Bookshelf · 2020 · review
British Journal of Pharmacology · 2008 · review
others in Anabolic & Androgenic