Metformin and progestins in women with atypical hyperplasia or endometrial cancer: systematic review and meta-analysis

Purpose: To assess metformin's effectiveness in adding it to progestin-based hormone therapy for treating atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC).

Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines (registration number CRD42023399094). We searched databases for studies up to March 2023, including randomized and non-randomized clinical trials in English.

Results: Out of 280 studies, 9 studies (1104 patients) were eligible. A total of 408 patients were allocated to receive metformin, and 696 patients entered the control group. Primary analysis focused on evaluating the CR showed a significant difference in patients with AEH treated with metformin (RR = 1.10, 95% CI 1.02-1.20, p = 0.02). Relapse rate (RR = 0.62, 95% CI 0.33-1.17, p = 0.14) was also evaluated. Secondary analysis indicated higher pregnancy rates (RR = 1.28, 95% CI 1.04-1.57, p = 0.02) with no significant difference in live birth rates (RR = 0.56, 95% CI 0.29-1.10, p = 0.09).

Conclusion: Combined therapy is effective. Metformin shows superiority to the standard regimen in achieving better CR rate in patients with AEH and benefits pregnancy rates but not recurrence or live birth rates. Therefore, the ideal fertility-sparing treatment for EC has not yet been determined and further clinical trials are needed.