Efficacy and safety of the levonorgestrel-releasing intrauterine system compared with oral progestogens for endometrial hyperplasia: a systematic review and meta-analysis of randomized controlled trials

Abstract

Abstract Objective To compare the efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with oral progestogens for histologic regression of endometrial hyperplasia using randomized controlled trial data. Methods A systematic review and meta-analysis of randomized controlled trials was conducted. The primary outcome was histologic regression. Log risk ratios (RRs) were pooled with inverse-variance random-effects models using restricted maximum likelihood (REML) estimation of τ² and Hartung-Knapp confidence intervals; a 95% prediction interval was calculated. Prespecified subgroup analyses and exploratory meta-regression by follow-up duration and oral progestogen type were performed. Safety outcomes were summarized narratively because reporting was heterogeneous. Results Twelve randomized controlled trials involving 1,199 randomized participants were included. LNG-IUS was associated with a higher likelihood of histologic regression than oral progestogens (RR, 1.21; 95% CI, 1.14–1.29; I² = 21.7%; 95% prediction interval, 1.08–1.36). The association was present in non-atypical hyperplasia (RR, 1.28; 95% CI, 1.14–1.44) and in the combined mixed-or-atypical subgroup (RR, 1.19; 95% CI, 1.10–1.28), which should not be interpreted as a pure atypical-hyperplasia estimate. Exploratory meta-regression did not identify follow-up duration (ratio of RRs per month, 0.996; 95% CI, 0.988–1.004; P = 0.310) or oral progestogen type (omnibus F(3, 8) = 0.58; P = 0.642) as statistically significant effect modifiers. Egger-type testing was not statistically significant ( P = 0.137), but with 12 trials it had limited ability to exclude publication bias. Conclusions In randomized trial data with extractable event counts, LNG-IUS was associated with higher histologic regression than oral progestogens. Safety evidence was insufficient for a comparative pooled conclusion, and treatment selection should account for histologic risk, surveillance feasibility, fertility goals, and patient preference. Trial registration INPLASY202690020

The authors' abstract, as published at the source. BMC Women s Health, 2026 · DOI ↗