Diane-35 combined with metformin in the treatment of polycystic ovary syndrome patients with atypical endometrial hyperplasia and early endometrial adenocarcinoma

Objective To explore the clinical efficacy and safety Diane-35 and metformin combined treatment for endometrial atypical hyperplasia (EAH) and early endometrial carcinoma (EEC) in polycystic ovary syndrome (PCOS) patients. Methods PCOS patients with endometrium lesion were re-cruited. All patients were treated with Diane-35 (1 tablet per day, for 21 d per month) plus metformin (1 000 mg, qd) for 6 months. Endometrial biopsies for pathological evaluation before, during and after treatment were conducted. Other clinical parameters included body weight (BW), body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), insulin area under curve (IAUC), homeostasis model assessment of insulin resistance (HOMA-IR) were detected as well. After successful conversion of endometrial lesions, we continued to give patients with Dydrogesterone (10 mg/d, for 14 d per month) and metformin. Results Totally 43 PCOS patients with endometrium lesion (30 EAH and 13 EEC) were re-cruited. After 6-month treatment, the endometrium in all PCOS patients was confirmed by pathological evaluation to be reversed to normal epithelia with Diane-35 plus metformin treatment. By the end of 6-month treatment, mean BMI, TT, FAI, HOMA-IR were decreased respectively (P<0.05), while SHBG were increased (P<0.05). The complete response (CR) rate was 100%. During 6-18 months of follow-up, 2 EAH patients relapsed, and both of whom did not continue to use progesterone therapy monthly; 2 EEC relapsed, who had complicated with ovary tumor. Conclusion Diane 35, a low-dose oral contraceptives with anti-androgen activity, when used in combination with metformin can completely revert the EEC and EAH to normal endometrial cell in PCOS patients, even in those who have been failure to high-dose progestin treatment before. Diane-35 with metformin combination treatment may be a good choice for the EAH and EEC in PCOS patients, which enables these patients to preserve the fertility. Key words: Polycystic ovary syndrome (PCOS); Endometrial atypical hyperplasia (EAH); Early endometrial carcinoma (EEC); Diane-35 combined with metformin