Hyperfunction of the Hypothalamic-Pituitary Axis in Women with Polycystic Ovarian Disease: Indirect Evidence for Partial Gonadotroph Desensitization*

To examine gonadotropin secretory frequency as a component of the disordered neuroendocrine regulation of gonadotropin secretion in women with polycystic ovarian disease (PCOD), we measured serum gonadotropin concentrations in 12 women with PCOD at 10-min intervals for periods of 12-24 h. The patterns of LH and FSH release in these patients were compared to the findings of 24 studies in 21 age-matched normal women during the early, mid- and late follicular phases (EFP, MFP and LFP) of their cycles. Serum sex steroid levels during the 12-24 h of study in the women with PCOD were compared to those in normal women studied during the follicular phase. The mean serum estradiol (E2) level in the women with PCOD was similar to that in normal women studied in the EFP, but lower than those in normal women in the MFP (P less than 0.05) and LFP (P less than 0.01). Mean serum estrone, however, was significantly higher in women with PCOD than in women in the EFP and MFP (P less than 0.05 and P less than 0.02, respectively), but lower than that in women in the LFP (P less than 0.02). Total and unbound testosterone (T) levels were significantly elevated in women with PCOD compared to those in normal women at all stages of the follicular phase (P less than 0.001). The mean serum LH concentration and LH pulse amplitude were markedly elevated in the women with PCOD compared to normal women at all three stages of the follicular phase (P less than 0.05 or less). In addition, LH pulse frequency was faster in women with PCOD 24.8 +/- 0.9 ( +/- SE) pulses/24 h than that in women in the EFP (15.6 +/- 0.7; P less than 0.01), MFP (22.2 +/- 1.1; P less than 0.05) and LFP (20.8 +/- 1.2; P less than 0.01). This increased LH pulse frequency in women with PCOD correlated with ambient serum E2 levels on the day of study (r = 0.84; P less than 0.001), but not with serum estrone, T, or unbound T. Repeat studies in four women with PCOD demonstrated a similarly abnormal gonadotropin secretory pattern in each. We conclude that 1) women with PCOD have an increase in both the amplitude and frequency of LH secretion compared to those in normally cycling women throughout the follicular phase; 2) the defect in women with PCOD is reproducible.(ABSTRACT TRUNCATED AT 400 WORDS)