Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Abstract

To evaluate the efficacy of medroxyprogesterone acetate (MA) plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and early-stage grade 1 endometrial adenocarcinoma (G1 EAC) and the recurrence rate after treatment. Sixty patients (aged 20-42 years) with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups (n=30) to receive oral MA treatment at the daily dose of 160 mg (control) or MA plus oral metformin (850 mg, twice a day) for at least 6 months. The treatment could extend to 12 months until a complete response (CR) was achieved, and follow-up hysteroscopy and curettage were performed every 3 months. For all the patients who achieved CR, endometrial expressions of IGFBP-rP1, p-Akt and p-AMPK were detected immunohistochemically. A total of 58 patients completed the treatment. After 9 months of treatment, 23 (76.7%) patients in the combined treatment group and 20 (71.4%) in the control group achieved CR; two patients in the control group achieved CR after converting to the combined treatment. The recurrence rate did not differ significantly between the control group and combined treatment group (30.0% vs 22.7%, P>0.05). Ten (35.7%) patients in the control group experienced significant weight gain of 5.7±6.1 kg, while none of the patients receiving the combined treatment exhibited significant body weight changes. Compared with the control group, the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression. Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC, and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.