What is the current evidence for oxymetholone (anabolic steroid) treatment?

Current Evidence for Oxymetholone Treatment

Oxymetholone (100 mg/day) is an effective anabolic steroid for specific conditions including HIV-associated wasting and hereditary angioedema prophylaxis, but its use is severely limited by significant dose-dependent hepatotoxicity occurring in 25-43% of patients, making it a second-line option that requires careful patient selection and intensive monitoring. 1, 2, 3

FDA-Approved Indications and Clinical Applications

HIV-Associated Wasting (Primary Evidence Base)

Efficacy in Eugonadal Patients:

• Oxymetholone 100 mg/day (50 mg twice daily) produces significant weight gain of 3.5 kg compared to 1.0 kg with placebo over 16 weeks in eugonadal HIV-positive patients 2, 3
• Body cell mass increases by 3.8 kg (12.4% of baseline) with the 100 mg/day regimen, representing clinically meaningful improvements in lean body mass 2, 3
• Functional improvements include increased appetite, food intake, well-being, and reduced weakness 1, 2

Dosing Considerations:

• The 100 mg/day regimen (50 mg twice daily) is equally effective as 150 mg/day (50 mg three times daily) but with significantly lower hepatotoxicity (25% vs 43% experiencing >5x baseline transaminase elevation) 2, 3
• ESPEN guidelines note that treatment at 100 mg/day resulted in increases in body weight, muscle mass, and functional parameters in placebo-controlled trials 1

Hereditary Angioedema Prophylaxis

Role in Treatment Algorithm:

• Oxymetholone is classified as a second-line anabolic steroid for long-term prophylaxis of hereditary angioedema, after plasma-derived C1 inhibitor and lanadelumab 4, 5
• It is particularly valuable in resource-limited settings where first-line therapies are unavailable 4
• Oxymetholone is contraindicated during pregnancy and breastfeeding due to teratogenic effects and should be discontinued at least 2 months before attempting conception 4
• It should generally be avoided in children before Tanner Stage V of puberty due to effects on growth and development 4, 5

Comparative Safety Profile:

• Oxandrolone demonstrates superior hepatic safety compared to oxymetholone among anabolic steroids, though both reduce attack frequency by >90% in most HAE patients 5

Other Investigated Conditions

Myelofibrosis:

• Long-term treatment at 3-5 mg/kg body weight produced normalization or substantial improvement in peripheral blood parameters in 9 of 15 treatment courses 6
• All 5 patients requiring regular blood transfusions before treatment achieved transfusion independence 6
• Significant effects were noted on both hemoglobin values and platelet counts 6

Anemia (FDA-Approved):

• FDA-approved for treatment of anemias caused by deficient red cell production 7
• Erythropoietic effects are well-documented, though hepatotoxicity remains the major limiting factor 7

Critical Safety Concerns and Monitoring Requirements

Hepatotoxicity (Primary Limiting Factor)

Incidence and Severity:

• Dose-dependent liver toxicity occurs in 25-43% of patients, with 35% in the 150 mg/day group, 27% in the 100 mg/day group, and 0% in placebo experiencing >5x baseline ALT elevation during controlled trials 1
• Cholestatic jaundice is the most important hepatic side effect 7
• Less common but serious hepatic effects include peliosis hepatis and hepatic tumor formation 7

Long-term Carcinogenic Risk:

• The National Toxicology Program found clear evidence of carcinogenic activity in female rats, with increased incidences of hepatocellular adenomas and carcinomas 8
• Equivocal evidence of carcinogenic activity in male rats based on increased subcutaneous tissue fibromas and adrenal pheochromocytomas 8

Mandatory Monitoring Parameters

Essential Laboratory Surveillance:

• Liver function tests (ALT, AST, gamma-GT) must be monitored regularly, as 25-43% of patients will develop significant transaminase elevations 5, 2, 3
• Lipid panel monitoring is required due to dose-related hypocholesterolemia observed in clinical studies 5
• Hematocrit monitoring is necessary due to dose-related erythrocytosis 5
• Prothrombin levels require monitoring when used with anticoagulants, with dosage adjustments as needed 9

Additional Monitoring:

• Growth parameters in children (if used despite recommendations against pediatric use) 5
• Blood pressure and cardiovascular risk factors 5
• Signs of virilization in women 5

Androgenic Side Effects

Common Adverse Effects:

• Acne, hirsutism, hair loss, clitoral/phallic enlargement, vocal changes, erectile tissue stimulation, gynecomastia, amenorrhea, and changes in libido and sexual potency 7
• These effects are inherent to all anabolic-androgenic steroids 7

Clinical Context and Guideline Recommendations

HIV Wasting Management

Position in Treatment Algorithm:

• ESPEN guidelines note that almost all controlled studies were conducted before HAART introduction, and efficacy in populations with access to modern antiretroviral drugs needs reassessment 1
• Other treatment options (including HAART optimization) should be exhausted before using anabolic steroids 1
• The effect of oxymetholone was "limited by significant dose-dependent liver toxicity in 30% of patients" according to ESPEN guidelines 1

Cancer Cachexia

Current Recommendations:

• ESPEN 2021 guidelines state there are insufficient consistent clinical data to recommend currently approved androgenic steroids to increase muscle mass in cancer patients 1
• ESPEN 2017 guidelines similarly concluded insufficient evidence exists to support recommendation of androgenic steroids for cancer cachexia 1
• Fluoxymesterone (20 mg/day) resulted in less appetite stimulation compared to megestrol acetate and dexamethasone in cachectic cancer patients 1

Critical Care and Post-ICU Recovery

Emerging Evidence:

• Oxandrolone (not oxymetholone) shows positive data for clinical and functional endpoints including 6-minute walk test, muscle strength, and quality of life in burn patients 1
• More research in broader ICU populations is needed to determine optimal candidates for testosterone/oxandrolone treatment 1

Drug Interactions Requiring Attention

Clinically Significant Interactions:

• Anticoagulants: Enhanced anticoagulant effect requiring prothrombin monitoring and dose adjustment 9
• Antidiabetic drugs: Diminished antidiabetic effect necessitating monitoring for hyperglycemia and upward dosage adjustment 9
• Corticosteroids (fludrocortisone): Enhanced tendency toward edema, requiring caution especially in patients with hepatic or cardiac disease 9
• Aspirin: Increased ulcerogenic effect and decreased pharmacologic effect of aspirin 9

Common Pitfalls to Avoid

Critical Clinical Errors:

• Using oxymetholone as first-line therapy when safer alternatives exist (plasma-derived C1 inhibitor for HAE, HAART optimization for HIV wasting) 1, 4
• Failing to implement intensive hepatic monitoring, given 25-43% of patients develop significant transaminase elevations 2, 3
• Prescribing during pregnancy or within 2 months of planned conception due to teratogenic risk 4
• Using in children before Tanner Stage V puberty without compelling indication 4, 5
• Employing doses higher than 100 mg/day, as 150 mg/day provides no additional efficacy but significantly increases hepatotoxicity (43% vs 25%) 2, 3

Outdated Clinical Practice:

• Relying on pre-HAART era data for HIV wasting management without considering modern antiretroviral therapy optimization 1
• Extrapolating cancer cachexia data to support use, when current guidelines explicitly state insufficient evidence exists 1