Anadrol

Oxymetholone (brand name Anadrol) is a synthetic anabolic-androgenic steroid and a derivative of testosterone. Chemically it is a 17alpha-alkylated, 17beta-hydroxy compound with a hydroxymethylene group at the C-2 position and a methyl group at C-17, belonging to the 5-alpha-androstane (dihydrotestosterone) structural class. Its full chemical name is 17beta-hydroxy-2-(hydroxymethylene)-17-methyl-5alpha-androstan-3-one.

The 17alpha-alkylation (addition of a methyl group at the 17-alpha carbon) is the structural feature responsible for oral bioavailability: it prevents rapid first-pass metabolism in the liver that would otherwise inactivate the steroid before it reaches systemic circulation. This modification is shared by several other orally active anabolic steroids and is also associated with the hepatotoxicity concerns noted with this drug class. Oxymetholone is approved by the US Food and Drug Administration for anemias caused by deficient red cell production.

Human study: A published review of clinical literature found that oxymetholone, a 17alpha-alkylated anabolic-androgenic steroid, has been studied for treatment of HIV-associated wasting, antithrombin III deficiency, pediatric growth impairment, and damaged myocardium, with varying degrees of success. The drug is FDA-approved for anemias caused by deficient red cell production. (PMID 11440282)

Human study: A clinical management guideline for Fanconi anemia notes that oral androgens including oxymetholone may transiently improve red blood cell and platelet counts in approximately 50% of affected individuals. The guideline also notes that all these therapies carry potential significant toxicity and recommends regular liver function tests and ultrasound monitoring during androgen therapy. (PMID 20301575)

Human study: A retrospective propensity-score-matched study of acquired aplastic anemia patients found that the one-year overall response rate to oxymetholone was 54.1% in non-severe aplastic anemia and 13.5% in severe or very severe aplastic anemia. Patients who responded to oxymetholone, even in the severe group, showed longer overall survival than non-responders. (PMID 36514313)

Human study: A real-world cost-effectiveness study in Thailand found that oxymetholone had significantly lower survival rates than rabbit-antithymocyte globulin plus cyclosporine in severe acquired aplastic anemia, while being associated with higher rates of blood transfusion need and hospitalization in the second year. Oxymetholone was identified as a viable lower-cost alternative in resource-limited settings despite inferior outcomes. (PMID 37393722)

Animal study: In a long-term mouse study using a Fanconi anemia model, oxymetholone treatment produced modest improvements in platelet count and hemoglobin levels in Fancd2-deficient animals. The combination of oxymetholone and metformin did not produce a significant synergistic effect on any hematopoietic parameter, and no adverse effects of either individual or combined therapy were observed over an 18-month treatment period. Note: Studied in Fancd2-/- mouse model of Fanconi anemia alongside metformin (PMID 38733122)

Human study: A clinical review identified hepatotoxicity as a major adverse effect of oxymetholone, with cholestatic jaundice being the most important hepatic side effect. Less common hepatic adverse effects include peliosis hepatis and hepatic tumor formation; androgenic side effects such as acne, hirsutism, hair loss, and gynecomastia are also reported. (PMID 11440282)

Human study: A clinical overview noted that children taking oxymetholone should be monitored regularly to ensure it does not interfere with normal growth, and that the drug is not always a first-line choice for HIV-associated wasting partly because of its potential for abuse. Drug interactions with cimetidine, paroxetine, and haloperidol are noted. (PMID 11365560)

Human study: The US National Toxicology Program's 15th Report on Carcinogens lists oxymetholone as a substance reasonably anticipated to cause cancer in humans, based on review of cancer studies in humans and animals and mechanistic data. This listing reflects the formal regulatory classification of oxymetholone within a US government public health document. (PMID 39456132)

Animal study: In a two-year NTP rat carcinogenicity study, oxymetholone produced clear evidence of carcinogenic activity in female rats including increased incidences of hepatocellular neoplasms, alveolar/bronchiolar neoplasms, and skin neoplasms, and equivocal evidence in male rats including subcutaneous fibromas and adrenal pheochromocytomas. In shorter-term studies, dose-related effects included erythrocytosis, hypocholesterolemia, reproductive organ toxicity (reduced sperm counts, ovarian dysgenesis), and organ weight changes in both rats and mice. Note: Administered by oral gavage in rats and mice (PMID 12571678)

Limitations:

Human study: This retrospective propensity-score-matched study of aplastic anemia patients had a relatively small matched sample of 74 patients, which may limit the generalizability of survival and response estimates. The authors note that close monitoring of therapeutic responses and switching therapy when remission is not detected are necessary given oxymetholone's limited efficacy in severe disease. (PMID 36514313)

Open questions: Several important questions remain unanswered by the available evidence. Most human efficacy data come from retrospective studies or older trials with limited sample sizes, making it difficult to establish robust dose-response or long-term safety profiles in patients. Whether the carcinogenic signals observed in rat studies (hepatocellular neoplasms, adrenal and lung tumors) translate meaningfully to human cancer risk at therapeutic exposures is not established. The combination of oxymetholone with metformin has been tested only in a mouse model of Fanconi anemia, and synergistic or additive effects in humans are unknown.

The degree to which timing of administration (circadian chronopharmacology) could meaningfully improve efficacy or reduce toxicity in clinical practice has not been evaluated in controlled trials. Long-term neurological outcomes—particularly dementia risk related to androgen dysregulation from AAS use broadly—have not been specifically studied for oxymetholone. Finally, whether findings in animal models regarding reproductive toxicity (sperm motility, ovarian dysgenesis, seminiferous tubule degeneration) apply to patients receiving therapeutic exposures remains unclear.