Factor Patricia Ann A, Pasamba Koleen C
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Philippine General Hospital, University of the Philippines Manila.
Department of Obstetrics and Gynecology, Philippine General Hospital, University of the Philippines Manila.
Acta Med Philipp. 2024 Jun 28;58(11):62-71. doi: 10.47895/amp.v58i11.8155. eCollection 2024.
Metformin has been studied for its anti-proliferative effects on endometrial cells, and it is hypothesized to have a synergistic effect with progestin therapy in suppressing endometrial cell proliferation. This systematic review and meta-analysis aimed to determine the efficacy of adjunctive metformin in the clinical regression of endometrial hyperplasia and early-stage endometrial carcinoma. There have been previous systematic reviews that investigated the role of metformin with progesterone for endometrial hyperplasia and endometrial cancer, but they have included retrospective cohorts, and are thus have higher risk of bias.
This meta-analysis followed the Cochrane methodology and adhered to the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) were included if they enrolled reproductive-aged women with endometrial hyperplasia (with and without atypia) and endometrial carcinoma who were treated with progestin and metformin. The primary outcome was the complete response rate at 12-16 weeks, and secondary outcomes included relapse rate, clinical pregnancy rate, and live birth rate. Subgroup analysis of endometrial hyperplasia without atypia vs hyperplasia with atypia and early endometrial cancer was also included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used for dichotomous data.
Six RCTs were included. The addition of metformin to progestin therapy may increase the complete response rate of endometrial hyperplasia without atypia (OR 5.12, 95% CI 1.17 to 22.41; n = 102) and live birth rates (OR 2.51, 95% CI 1.34 to 4.69; n = 188) compared to progestin therapy alone, but the certainty of the evidence is low. Metformin did not have a significant effect on the clinical response of endometrial hyperplasia with atypia and endometrial carcinoma, relapse rates, and clinical pregnancy rates.
Current evidence is uncertain on the potential benefit of metformin with progestin in endometrial hyperplasia and carcinoma. Future high-quality randomized controlled trials with larger sample sizes and longer follow-up periods are needed to support practice recommendations.
二甲双胍对子宫内膜细胞的抗增殖作用已得到研究，并且据推测它在抑制子宫内膜细胞增殖方面与孕激素疗法具有协同作用。本系统评价和荟萃分析旨在确定辅助使用二甲双胍在子宫内膜增生和早期子宫内膜癌临床消退中的疗效。之前已有系统评价研究了二甲双胍联合孕激素对子宫内膜增生和子宫内膜癌的作用，但这些研究纳入的是回顾性队列，因此存在较高的偏倚风险。
本荟萃分析遵循Cochrane方法并遵守PRISMA 2020指南。纳入的随机对照试验（RCT）需纳入接受孕激素和二甲双胍治疗的患有子宫内膜增生（有或无不典型增生）和子宫内膜癌的育龄妇女。主要结局是12 - 16周时的完全缓解率，次要结局包括复发率、临床妊娠率和活产率。还包括对无不典型增生的子宫内膜增生与不典型增生及早期子宫内膜癌的亚组分析。二分类数据采用比值比（OR）和95%置信区间（CI）。
纳入了6项RCT。与单独使用孕激素疗法相比，在孕激素治疗中添加二甲双胍可能会提高无不典型增生的子宫内膜增生的完全缓解率（OR 5.12，95% CI 1.17至22.41；n = 102）和活产率（OR 2.51，95% CI 1.34至4.69；n = 188），但证据的确定性较低。二甲双胍对不典型增生的子宫内膜增生和子宫内膜癌的临床反应、复发率及临床妊娠率没有显著影响。
目前关于二甲双胍联合孕激素治疗子宫内膜增生和癌的潜在益处的证据尚不确定。需要未来进行更大样本量和更长随访期的高质量随机对照试验来支持实践建议。
