Oxandrolone for burn patients: a systematic review and updated meta-analysis of randomized controlled trials from 2005 to 2025

Abstract

Severe burn injuries induce hypermetabolism, leading to protein catabolism, impaired wound healing, and increased infection risk. Burn patients often experience androgen depletion, exacerbating these issues. Oxandrolone, a synthetic anabolic steroid, has shown promise in counteracting these metabolic disturbances. This updated meta-analysis evaluates the efficacy and safety of oxandrolone in burn patients, incorporating recent studies, pediatric populations, long-term outcomes, and combination therapies. This PRISMA 2020-compliant systematic review searched 9 databases (PubMed, Embase, Cochrane, WOS, WHO-ICTRP, CNKI, VIP, Wanfang, CBMdisc) for RCTs published between 2005 and 2025 using validated strategies combining controlled vocabulary (MeSH/Emtree) and free-text terms for burn/trauma AND androgen analogs (e.g., oxandrolone, nandrolone). Included trials compared androgen analogs vs. controls (placebo/standard care) in burn patients, reporting ≥ 1 predefined outcome: (1) Lean body mass (recovery phase, ≥ 14 days post-burn); (2) Mild side effects (hepatic dysfunction [ALT/AST ≥ 2 × ULN] or edema); (3) Infections; (4) Mortality; (5) Surgical procedures; (6) LOS/TBSA; (7) Absolute LOS. Dual-independent screening, data extraction, and risk-of-bias assessment (Cochrane RoB 2.0 per outcome) were performed. Random-effects meta-analyses generated standardized mean differences (SMD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% CIs. Fourteen RCTs (2005–2025; n = 2822 patients: 1203 intervention vs. 1619 controls) demonstrated significant reductions in surgical procedures (SMD = − 1.25; 95% CI − 2.45 to − 0.04; p = 0.04; I2 = 97.2%) and length of stay normalized to TBSA (LOS/TBSA) (SMD = − 1.07; 95% CI − 2.43 to 0.29; p = 0.007; I2 = 98.1%), alongside enhanced anabolic recovery evidenced by increased weight gain (SMD = 0.58; 95% CI − 1.21 to 2.38; p < 0.001) and lean mass (SMD = 1.30; 95% CI − 0.47 to 3.24; p < 0.001; I2 ≥ 95.0%). However, no mortality benefit was observed (RR = 1.04; 95% CI 0.47–2.32; p = 0.913; I2 = 66.5%), with unchanged infection rates (RR = 0.83; 95% CI 0.67–1.02; p = 0.639) and no improvement in donor site healing (SMD = − 1.48; 95% CI − 2.18 to 0.77; p = 0.116). Safety analysis revealed a non-significant increase in treatment-related side effects (hepatic dysfunction/edema; RR = 1.82; 95% CI 0.52–6.42; p = 0.34), notably higher transaminase elevations in adults (19% vs. 5% placebo; p = 0.002). Oxandrolone demonstrates clinical utility in burn management by significantly reducing surgical burden (SMD = − 1.25; p = 0.04), shortening hospitalization (LOS/TBSA SMD = − 1.07; p = 0.007), and enhancing anabolic recovery (weight gain SMD = 0.58; lean mass SMD = 1.30; both p < 0.001). However, extreme heterogeneity (I2 ≥ 95.0%) and temporal limitations necessitate cautious interpretation. Critically, it confers no mortality benefit (RR = 1.04; p = 0.913), fails to reduce infections (RR = 0.83; p = 0.639), and elevates hepatotoxicity risk in adults (19% vs. 5%; p = 0.002). These findings support its adjunctive role in metabolic rehabilitation but mandate risk-stratified implementation.