Ormeloxifene Versus Norethisterone for Anovulatory Abnormal Uterine Bleeding: An India-Based Systematic Review and Meta-Analysis

Abnormal uterine bleeding due to ovulatory dysfunction (AUB-O) is a frequent gynecological problem affecting women of reproductive and perimenopausal age. While norethisterone, a synthetic progestogen, has been widely used for medical management, ormeloxifene, a selective estrogen receptor modulator, has recently emerged as a promising alternative. The objective of this study is to compare the efficacy and safety of ormeloxifene versus norethisterone in the treatment of AUB-O. A systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with PROSPERO (CRD42024514294). A comprehensive search of PubMed, Google Scholar, Web of Science, and the Cochrane Library was performed up to 2025. Eligible studies included randomized controlled trials and prospective comparative studies evaluating ormeloxifene against norethisterone in women with AUB-O. Outcomes assessed were hemoglobin improvement, reduction in endometrial thickness, and change in Pictorial Blood Assessment Chart (PBAC) score. Data were extracted independently by two authors and analyzed using RevMan 5.4 (The Cochrane Collaboration, Oxford, UK) with a random-effects model. Five studies comprising 661 women were included (331 received ormeloxifene; 330 received norethisterone). Ormeloxifene significantly improved hemoglobin levels compared with norethisterone (standardized mean difference (SMD) = 0.81 g/dL, 95% CI 0.14-1.47; p < 0.00001; I² = 93%). It was also superior in reducing endometrial thickness (SMD = -0.74 mm, 95% CI -1.48 to -0.01; p < 0.00001; I² = 91%) and lowering PBAC scores (SMD = -1.06, 95% CI -1.25 to -0.87; p < 0.00001; I² = 0%). This meta-analysis suggests that ormeloxifene is more effective than norethisterone in improving clinical outcomes of AUB-O, with better control of menstrual blood loss, hemoglobin levels, and endometrial thickness. Larger, high-quality multicenter trials with longer follow-up are warranted to confirm long-term safety and efficacy.