Hysteroscopic Curettage Followed by Megestrol Acetate Plus Metformin as a Fertility-Sparing Treatment for Women with Atypical Endometrial Hyperplasia or Well-Differentiated Endometrioid Endometrial Carcinoma

Abstract

Background: In reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC.

Methods: We retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model.

Results: The study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration ⩾9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births.

Conclusions: Hysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.

Keywords: Endometroid endometrial cancer; fertility-sparing treatment; hysteroscopy; megestrol acetate; metformin.

Figure 1.

Flowchart of the study. AEH indicates atypical endometrial hyperplasia; CR, complete response; EC, endometrial carcinoma; PR, partial response; SD, stable disease.

Figure 2.

Treatment outcomes of the AEH and EEC subgroups. AEH indicates atypical endometrial hyperplasia; CR, complete response; EEC, endometrioid endometrial carcinoma; PR, partial response; SD, stable disease.

Figure 3.

Recurrence-free survival curves of the patients who received conservative treatment shorter or longer than 9 months: (A) the whole cohort, (B) the AEH subgroup, and (C) the EEC subgroup. AEH indicates atypical endometrial hyperplasia; EEC, endometrioid endometrial carcinoma; P values were determined by the log-rank test.