Increased GnRH pulse generation in the hypothalamus increases LH pulse frequency, amplitude as well as 24-hour mean serum concentrations. Increased luteinizing hormone (LH) secretion together with enhanced theca cell responsiveness drives the production of excess androgen. The increased androgen production may inhibit sex steroid (estradiol/progesterone) negative feedback on hypothalamic Gonadotropin Releasing Hormone (GnRH) pulse generation resulting in the rapid LH pulse frequency seen in PCOS women. Additionally, increased androgens are associated with android obesity, visceral fat deposition, and dyslipidemia, all of which may contribute to insulin resistance and compensatory hyperinsulinemia. Hyperandrogenemia, obesity, and hyperinsulinemia decrease Sex Hormone Binding Globulin (SHBG), thereby increasing free, bioactive androgens. Exacerbating the ovarian and adrenal androgen excess is the observation that PCOS women have enhanced peripheral and hepatic 5a reductase activity as well as high concentrations of 5a reductase in the follicular fluid. Increased androgen production may also have direct effects on the ovary to increase follicle number, follicle size, and possibly enhance granulosa cell responsiveness to Follicle Stimulating Hormone (FSH).
