The Comparative Effect of Combination of Metformin and Megestrol Acetate With Megestrol Acetate Alone on Endometrial Growth Disorders

Objectives: Endometrial hyperplasia has an affinity for progression toward endometrial carcinoma. This study was conducted to compare the effect of metformin plus megestrol acetate with megestrol acetate alone on endometrial histology in the patients with endometrial proliferative and hyperplastic disorders. Materials and Methods: In a single-blind clinical trial, 96 patients with abnormal uterine bleeding and endometrium with irregular or hyperplastic glands with or without atypical foundations were divided randomly into 2 equal groups. Group1 received metformin 500 mg twice a day plus megestrol acetate 40 mg daily for 3 months and group 2 received megestrol acetate 40 mg/d for 3 months. The treatment response was evaluated using pathologic samples of endometrial biopsies 2 weeks after completing the treatment. Results: In both groups, endometrial hyperplasia was resolved in most cases. Significant decrease was observed within groups in the endometrial thickness before and after the intervention. Comparison of thickness between 2 groups showed that in the megestrol acetate group, after intervention, significant decrease in the endometrial thickness was revealed (12.73 ± 6.04 mm [group 1], versus 8.55 ± 3.43 mm [group 2], P < 0.001). Lack of response to treatment was seen in 7% of group 1 and 4.9% of group 2 (P=0.68). None of the groups showed any complications and there was no hysterectomy. Conclusions: Both treatment modalities were effective in treating proliferative and hyperplastic disorders. However, the response to treatment in the megestrol group was greater than that in the megestrol plus metformin group.