Evaluation of the Effect of Additive Metformin to Progesterone on Patients with Endometrial Hyperplasia

Document Type: Research Paper


1 Department of Gynecology and Obstetrics, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran.

2 School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.


Background and Objectives: Endometrial hyperplasia (EH) is an abnormal overgrowth of endometrium that may lead to endometrial cancer, especially when accompanied by atypia. The treatment of EH is challenging, and previous studies report conflicting results. Metformin (dimethyl biguanide) is an anti-diabetic and insulin sensitizer agent, which is supposed to have antiproliferative and anticancer effects and the potential to decrease cell growth in endometrium. While some studies have evaluated the anticancer effect of metformin, studies on its potential effect on endometrial hyperplasia are rare. To address this gap, in this comparative trial study, we evaluate the effect of additive metformin to progesterone in patients with EH. Methods: In this clinical trial, 64 women with EH were randomized in two groups. The progesterone-alone group received progesterone 20 mg daily (14 days/month, from the 14th menstrual day) based on the type of hyperplasia, and the progesterone-metformin group received metformin 1000 mg/day for 3 months in addition to progesterone. Duration of bleeding, hyperplasia, body mass index (BMI), and blood sugar (BS) of the patients were then compared between the two groups. Findings: NA mean age of 44.5 years, mean BMI of 29 kg/m2 and mean duration of bleeding of 8 days were calculated for the study sample. There was no significant difference in age, BMI, gravidity, bleeding duration, and duration of disease at baseline between the two groups. While all patients in the progesterone-metformin group showed bleeding and hyperplasia improvement, only 69% of the progesterone-alone patients showed such an improvement, with the difference between the two groups being significant (P = 0.001). Although the difference between two groups in the post treatment endometrial thickness was not significant (P = 0.55), post treatment BMI in the progesterone-metformin group was significantly lower than in the progesterone-alone group (P = 0.01). In addition, the BS reduction in the progesterone-metformin group was significantly larger than that in the progesterone-alone group (P = 0.001). Conclusions: Our results indicated that administration of progesterone 20 mg/day plus metformin 1000 mg/day can significantly decrease bleeding duration, hyperplasia, BMI and BS in women with EH.