Introduction To assess the long-term efficacy of metformin in megestrol acetate(MA)-based fertility-sparing treatment for patients with endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC).

Methods Patients with EAH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).

Results The complete remission rate, disease-free survival (DFS) rate and pregnancy rate had no significant difference between two treatment groups. However, the DFS rate was higher in the metformin plus MA group than in the MA-only group in non-obese (body mass index<28 kg/m²) patients with EAH (hazard ratio [HR] = 2.677, 95% confidence interval [CI] = 1.066–6.727; Log Rank P = 0.029), while had a lower tendency in obese patients with EAH (HR = 0.224, 95% CI = 0.045–1.223; Log Rank P = 0.062). According to cox proportional hazards regression analysis, undergoing assisted reproductive treatment (HR = 2.358, 95% CI = 1.069–5.204; Log Rank P = 0.034) was identified as an independent risk factor for recurrence, whereas younger patients were found to have a higher probability to achieve pregnancy (HR = 0.568, 95% CI = 0.332–0.973; Log Rank P = 0.039).

Conclusion/Implications Currently, there is no sufficient evidence to support that the utilization of metformin plus MA can significantly improve the prognosis of patients with EAH or EEC compared to MA monotherapy. However, obese patients with endometrial lesions may benefit from the addition of metformin.