**2.3. Prevention of endometrial hyperplasia**

The modified metabolic background associated with PCOS is basically characterized by unbalanced estrogen serum levels due to lack of progesterone production. Left untreated, the main effects of this modified environment leads to atypical endometrial hyperplasia, and endometrial dysfunction-induced infertility [18].

Even though progesterone-based oral contraceptive therapy is often efficacious [19], approximately 30% of women with PCOS fail to respond to such treatment [20] and progress to the development of atypical hyperplasia and further transformation to endometrial cancer [21].

The mechanism of progesterone resistance is determined at molecular level and based on the imbalance of two progesterone receptor (PR) isoforms PRA and PRB. Patients with PCOS have a modified ratio of PRA to PRB receptors present on stromal and epithelial cells of endometrium [21].

Progesterone resistance is associated with insulin resistance [20] and this way, a new perspective in the prevention of endometrial hyperplasia can be contoured: targeted therapy on reducing insulin resistance may benefit both endometrial tissue and serum hyperinsulinemia.
