Efficacy and Safety of Ormeloxifene Versus Conventional Hormonal Therapy in Women With Non-structural Abnormal Uterine Bleeding: A Systematic Review and Meta-Analysis.

BACKGROUND

Abnormal uterine bleeding (AUB) is a major gynecological complaint that significantly impacts women's quality of life, particularly during their reproductive years. Non-structural AUB presents a therapeutic challenge due to the absence of an identifiable anatomical cause. Conventional hormonal therapies have been in use for a long time, but they are frequently associated with side effects. The advent of ormeloxifene (ORM), a non-steroidal selective estrogen receptor modulator, has emerged as a promising alternative. This systematic review and meta-analysis were conducted to provide a thorough assessment of the efficacy and safety of ORM compared to various hormonal therapies for AUB in cases where no structural cause is identified. The present study is the first meta-analysis, to the best of our knowledge, that compared ORM to conventional hormonal therapy in the management of non-structural AUB.

Methods

This systematic review and meta-analysis were conducted with adherence to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was conducted across various databases, including PubMed, Google Scholar, Web of Science, and Cochrane Library, from the inception of the databases to July 31, 2024. Eligible studies included randomized controlled and quasi-randomized trials that compared ORM with hormonal therapy and reported on the desired outcomes. The primary outcome was to compare the Pictorial Blood Loss Assessment Chart scores in women with non-structural AUB receiving either ORM (intervention) or hormonal therapy (control). Secondary outcomes included hemoglobin (Hb) levels, endometrial thickness, and adverse events (side effects).

RESULTS

Out of the 113 records that the first search produced, 45 articles were evaluated in full text. Five randomized controlled trials with 516 participants and two non-randomized studies with 140 participants were identified and included in the analysis. Data were extracted, and quality assessment was performed using the revised Cochrane risk-of-bias tool for randomized trials. Pooled analysis revealed that ORM was more efficacious than hormonal therapy in improving menorrhagia among women with non-structural AUB (mean difference or MD=-32.49, 95% confidence interval or CI (-52.78, -12.20), p=0.002). Similarly, there was a significant overall effect on the mean Hb level in patients after therapy with ORM (MD=0.72, 95% CI (0.28, 1.16), p=0.001). However, no significant difference was observed in the endometrial thickness in either group (MD=-0.81, 95% CI (-1.70, 0.09), p=0.08). Weight gain as an adverse event was observed to be significantly higher (MD=0.13, 95% CI (0.03, 0.52), p=0.004) in women using hormonal therapy, whereas amenorrhea was found more among women receiving ORM (MD=12.11, 95% CI (4.61,31.85), p=<0.00001).

Conclusion

The results of this study supplement the body of knowledge regarding the safety and effectiveness of ORM, although this study mostly consisted of randomized controlled trials. Further, multicenter studies with larger sample sizes are needed in the future to determine additional aspects, such as cost-effectiveness, patient satisfaction, and improvements in quality of life with ORM.