Elevations in unbound serum estradiol as a possible mechanism for inappropriate gonadotropin secretion in women with PCO

Twenty-three women considered to have polycystic ovarian disease (PCO) were studied in an effort to better understand the mechanism of inappropriate secretion (IGS) which is so characteristic of these women. Criteria for PCO included oligomenorrhea, infertility, an obesity index (ponderal index, PI) < 12, and an LH:FSH ratio > 3. The mean +/- SE weight and PI for this group were 175 +/- 7.5 lbs. and 11.2 +/- 0.2 respectively. Weight was not correlated with steroid levels in PCO or control women. The mean (+/- SE) of serum androgen concentrations (DHEA-S: 2.9 +/- 0.5 micrograms/ml; androstenedione: 2.6 +/- 0.3 ng/ml; and testosterone: 47 +/- 5 ng%) were all significantly higher than those in control women (p < .05). Total serum estradiol (E2) was comparable to those of controls in the follicular phase, while estrone (E1): E2 ratios averaged 2:1. Serum sex hormone binding globulin-binding capacity (SHBG-BC) averaged 56.8 +/- 4.2 nM which was significantly lower than that of controls (p < .05). The percent unbound E2 was significantly elevated in PCO (62% vs 37%). The mass of unbound E2 was also significantly higher in PCO women (40 +/- 3 pg/ml) than in controls (17 +/- 2 pg/ml) (p < .005). Serum LH:FSH ratios had a positive correlation with the relative and absolute concentration of unbound E2. In control women, unbound E2 correlated significantly with LH levels. This suggests that IGS characteristically found in PCO patients and exemplified by elevated LH;FSH ratios, is the result of the feedback response to elevated levels of unbound (i.e., biologically active) E2.