B tier · viable
Uniquely among these five compounds it carries a genuine randomized human evidence base — 14 RCTs and 2,822 patients in a 2025 burn meta-analysis plus a 5-year pediatric RCT — but effect sizes are heterogeneous, no mortality benefit is shown, and the FDA formally determined the product was withdrawn for reasons of safety or effectiveness.
oxandrolone
Oxandrolone is the only compound in this group with a substantial modern randomized evidence base, concentrated almost entirely in severe-burn catabolism and paediatric growth indications. That evidence appears to show reproducible gains in bone mineral content and height velocity and reduced length of stay, but it does not demonstrate a mortality benefit and is limited by extreme statistical heterogeneity.
the explanation
Oxandrolone is an oral steroid that was genuinely studied in hospitals, mostly in children with severe burns, where trials suggest it helped them rebuild bone and grow. Despite that real research record, US regulators pulled it from the market in 2023 and formally classified the withdrawal as being for safety or effectiveness reasons.
regulatory status
US Schedule III controlled substance; UK Class C (Misuse of Drugs Act, Schedule 4 Part II). US marketing approval withdrawn.
Oxandrolone historically held FDA approval as adjunctive therapy for weight gain after weight loss following extensive surgery, chronic infection, or severe trauma, and for bone pain in osteoporosis. FDA withdrew approval of the Oxandrin NDA and four oxandrolone ANDAs in June 2023, and on 8 September 2023 published a determination under 21 CFR 314.161 that the tablets 'were withdrawn for reasons of safety or effectiveness,' adding that it will 'not accept or approve ANDAs that refer to this drug product.' It therefore retains NO approved US medical indication. It remains Schedule III under the Controlled Substances Act and Class C in the UK.
how it works · proposed mechanism
Oxandrolone acts as an androgen receptor agonist whose 2-oxa and 17α-methyl modifications confer oral bioavailability and a comparatively high anabolic-to-androgenic ratio.
Androgen receptor agonism
Oxandrolone binds the nuclear androgen receptor, which translocates to the nucleus and modulates transcription of genes governing skeletal muscle protein synthesis. The resulting nitrogen retention is the proposed basis for its anti-catabolic effect in burn injury.
2-oxa ring substitution
Replacement of the C2 carbon with oxygen in the A-ring distinguishes oxandrolone from other DHT derivatives and is associated with resistance to hepatic metabolism. This contributes to oral activity and to a larger renal elimination fraction than most 17α-alkylated agents.
17α-alkylation and first pass
The 17α-methyl group sterically blocks hepatic 17β-hydroxysteroid dehydrogenase oxidation, permitting oral dosing to reach systemic circulation. This same modification is the structural feature responsible for the cholestatic and neoplastic liver injury documented across this drug class.
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 randomized evidence is real but narrow — it addresses severe burn catabolism and paediatric growth, not general body composition in healthy adults, and the pooled analyses carry heterogeneity of I² ≥ 95% that the authors themselves flag as limiting interpretation. A regulator that reviewed this same record concluded the product's risks were not outweighed by demonstrated benefit and removed it from the US market.
key published findings
- Human RCT (5-year follow-up, 119 severely burned children ≥30% TBSA, 35 treated vs 84 control): whole-body bone mineral content significantly increased from 4.5 years post-burn (p<0.02); lumbar spine BMD z-score 0.055 in treated vs −0.73 in controls (p=0.0009).
- Human RCT (same cohort): 12% (6/49) of control children had BMD z-scores below −2.0 versus 0% of the oxandrolone cohort (p=0.039); height velocity was greater at post-burn year 1 (p=0.0008) and year 2 (p=0.02).
- Human meta-analysis (14 RCTs, 2,822 patients, 2005-2025): significant reduction in number of surgical procedures (SMD −1.25, 95% CI −2.45 to −0.04, p=0.04) but I²=97.2%.
- Human meta-analysis (same): NO mortality benefit (RR 1.04, 95% CI 0.47-2.32, p=0.913) and no change in infection rate (RR 0.83, 95% CI 0.67-1.02, I²=0.0%); lean body mass in the recovery phase was not significantly improved (SMD 0.14, 95% CI −2.02 to 2.29).
- Human safety signal (same meta-analysis): adults showed higher transaminase elevations than placebo, 19% versus 5% (p=0.002), while the paediatric 5-year RCT reported no significant ALT/AST alteration and no liver enlargement.
limitations of the evidence
- Extreme statistical heterogeneity (I² ≥ 95%) across the principal pooled outcomes means the summary effect estimates are unstable and may not represent any single population.
- The evidence base is dominated by severe-burn and paediatric-growth populations from a small number of centres, and does not generalise to healthy adults or to body-composition endpoints.
- Long-term oncological and cardiovascular outcomes were not the endpoint of these trials, and the FDA's own review concluded the safety profile was not offset by demonstrated efficacy.
documented safety signals
- HEPATOTOXICITY (17α-alkylated class): NIH LiverTox documents that acute cholestasis occurs in approximately 1% of patients treated with 17α-alkylated androgens, typically arising within 1-4 months but with onset delayed up to 6-24 months. Cholestasis has NOT been described with unmodified testosterone, implicating the 17α-alkyl group specifically.
- PELIOSIS HEPATIS: blood-filled enlarged hepatic sinusoids and cysts, documented after 2-27 months of therapy; may be asymptomatic or present catastrophically with hepatic rupture and haemorrhage. Documented for oxandrolone despite its historical reputation for relative hepatic safety.
- HEPATIC ADENOMA AND HEPATOCELLULAR CARCINOMA: LiverTox reports tumours arising typically after 5-15 years of long-term androgen use, though cases within 2 years exist; some adenomas regress spontaneously on discontinuation, which does not eliminate the risk of haemorrhage or malignant transformation.
- TRANSAMINASE ELEVATION: 19% of adult burn patients versus 5% on placebo (p=0.002) in pooled RCT data.
- ADVERSE LIPID EFFECTS: oral 17α-alkylated androgens as a class markedly suppress HDL cholesterol and raise LDL, an effect driven by induction of hepatic triglyceride lipase; this is a recognised class effect of oral alkylated agents rather than of parenteral testosterone.
- CARDIOMYOPATHY AND ATHEROSCLEROSIS: Baggish et al. (Circulation 2017, n=140 weightlifters) found reduced LV ejection fraction in AAS users versus non-users (52±11% vs 63±8%, p<0.001), impaired diastolic relaxation velocity (9.3±2.4 vs 11.1±2.0 cm/s, p<0.001), and greater coronary plaque volume (p=0.012), with atherosclerotic burden scaling with lifetime dose (0.60 SD units per 10 years, p=0.008).
- HPG AXIS SUPPRESSION: exogenous androgen exposure suppresses hypothalamic GnRH and pituitary LH/FSH release, producing testicular atrophy, impaired spermatogenesis and suppressed endogenous testosterone, with recovery that may be prolonged or incomplete.
- VIRILISATION IN WOMEN: documented and partly IRREVERSIBLE — voice deepening, hirsutism, male-pattern baldness, clitoral enlargement and menstrual disturbance. Voice change and clitoromegaly in particular do not reliably reverse on discontinuation.
- GROWTH-PLATE EFFECTS IN ADOLESCENTS: androgens accelerate epiphyseal maturation and can cause premature growth-plate closure with permanent loss of adult height; this risk is the reason paediatric use requires skeletal monitoring.
- REGULATORY SAFETY DETERMINATION: FDA determined in September 2023 that the product was withdrawn for reasons of safety or effectiveness and will not approve generics referencing it.
- OTHER: thromboembolic events and lipid-mediated cardiovascular risk are carried in the product's historical labelling warnings.
identity
| full name | Oxandrolone (17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one) |
| category | Anabolic & Androgenic |
| modality | steroid |
| formula | C19H30O3 |
| molar mass | 306.4 g/mol |
| cas | 53-39-4 |
| half-life | ~9.4-10.4 h; ~13.3 h reported in elderly subjects |
laboratory handling
| storage | Reference standard material is typically stored as a dry powder at controlled room temperature, protected from light and moisture; long-term storage of analytical standards is commonly at −20 °C in sealed, desiccated containers. |
| solubility | Practically insoluble in water; soluble in ethanol, methanol, chloroform and DMSO. Reported as a white crystalline solid. |
| co-studied with | This index does not describe combination use. Concurrent use of multiple 17α-alkylated oral androgens compounds hepatic and lipid toxicity in an additive-to-synergistic fashion, and combined exposure is a recurring feature of the case literature on cholestatic injury and peliosis hepatis. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedLiverTox: Clinical and Research Information on Drug-Induced Liver Injury, NIDDK/NIH (NBK548931) · 2020 · official
Federal Register, US Food and Drug Administration · 2023 · official
Shock / Shriners Hospitals for Children–Galveston (PMC4792676) · 2016 · randomized
World Journal of Emergency Surgery · 2025 · reviews
Surgery (PMID 15300183) · 2004 · randomized
Circulation · 2017 · observational
others in Anabolic & Androgenic