Clinicopathologic Study of Endometrial and Hormonal Changes after Metformin Therapy in Patients with Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is a common complex genetic condition of women in the reproductive age. PCOS is a heterogeneous syndrome characterized by clinical/biochemical androgen excess, ovulatory dysfunction and polycystic ovaries. Metformin therapy has been proved to improve fertility in patients with PCOS, inducing not only high ovulation and pregnancy rates, but also reducing the incidence of miscarriages. Aim of the Work: This study was aimed to evaluate the effects of metformin therapy on hormonal profile and endometrial tissue, including pattern of immunohistochemical expression of androgen receptors (AR), in patients with PCOS. Patients and Methods: 100 patients with PCOS were included in this study. Each investigated case was submitted to detailed medical history, clinical examination that included body hair distribution, body weight, height and body mass index (BMI), transvaginal ultrasound, laboratory investigations ( included fasting insulin, free testosterone, LH and FSH levels). Endometrial pipelle samples were taken for histopathological evaluation and assessment of androgen receptor expression. These investigations were done before and after three months of metformin treatment. Results: A significant decrease of BMI of the investigated cases after metformin therapy was observed (P value <0.003). There was a significant decrease of LH level after metformin therapy from 9.17±2.84 Miu/ml to 6.18±3.6 Miu/ml and of fasting insulin level from 14.3±4.3 to 8.2±5.9. Insignificant increase of FSH level from 3.87±1.8 to 4.85±2.6 and also insignificant decrease of free testosterone level from 1.58±o.83 to 1.38±1.4 were also observed. Histopathological results of the endometrial specimens before metformin therapy revealed histologic features of early proliferative endometrium in 64 cases, 20 cases with a late proliferative endometrium and examination of the remaining 16 cases revealed features of simple endometrial hyperplasia. Among the 64 cases diagnosed as early proliferative endometrium before the therapy, 60 cases showed features of a late proliferative endometrium after treatment and the remaining 4 cases showed no histomorphologic changes. Among the 20 cases diagnosed as a late proliferative endometrium before therapy, 6 cases showed features of early secretory phase after therapy, 6 cases showed features of mid-secretory endometrium while the remaining 8 cases showed a late secretory endometrium that indicate successful ovulation after therapy. Regression of hyperplasia after therapy was noted in 6 of the 16 cases diagnosed as simple endometrial hyperplasia. Immunohistochemical (IHC) results revealed marked increase in endometrial AR expression in patients with PCOS compared to the normal fertile controls (p<0.004). Also, a significant decrease of AR expression in endometrial epithelial and stromal cells after metformin administration in patients with PCOS was noted (p<0.003). Conclusion: Metformin therapy restores normal menstrual cyclicity in patients with PCOS, induces ovulation and showing significant decrease in endometrial AR expression. [ABSTRACT FROM AUTHOR]