DETERMINANTS OF ABNORMAL GONADOTROPIN-SECRETION IN CLINICALLY DEFINEDWOMEN WITH POLYCYSTIC-OVARY-SYNDROME

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of reprod uctive age women characterized in its broadest definition by the prese nce of oligomenorrhea and hyperandrogenism and the absence of other di sorders. Defects of gonadotropin secretion, including an elevated LH l evel, elevated LH to FSH ratio, and an increased frequency and amplitu de of LH pulsations have been described, but the prevalence of these d efects in a large, unbiased population of PCOS patients has not been d etermined. Sixty-one women with PCOS defined by oligomenorrhea and hyp erandrogenism and 24 normal women in the early follicular phase had LH samples obtained every 10 min for 8-12 h. Pool LH levels from the fre quent sampling studies were within the normal range in the 9 PCOS pati ents (14.8%) who were studied within 21 days after a documented sponta neous ovulation. Excluding these post-ovulatory patients, 75.0% of the PCOS patients had an elevated pool LH level (above the 95th percentil e of the normal controls), and 94% had an elevated LH to FSH ratio.In the anovulatory PCOS patients, pool LH correlated positively with 17-O H progesterone (R = 0.30, P = 0.03), but not with estradiol, estrone, testosterone, androstenedione, or DHEA-S. Pool LH and LH to FSH ratio correlated positively with LH pulse frequency (R = 0.40, P = 0.004 for pool LH, and R = 0.39; P = 0.005 for LH/FSH). There was also a strong negative correlation between pool LH and body mass index (BMI) (R = - 0.59, P < 10(-5)). The relationship between BMI and LH secretion in th e PCOS patients appeared to be strongest with body fatness, as pool LH was correlated inversely with percent body fat, whether measured by s kinfolds (R = -0.61, P < 10(-5)), bioimpedance (R = -0.55, P < 10(-4)) , or dual energy x-ray absorptiometry (DEXA) (R = -0.70, P = 0.001; n = 18 for DEXA only). By DEXA, the only body region that was highly cor related with pool LH was the trunk (R = -0.71, P = 0.001). The relatio nship between body fatness and LH secretion occurred via a decrease in LH pulse amplitude (R = -0.63, P < 10(-5) for BMI; R = -0.58, P < 10( -4) for bioimpedance; and R = -0.64, P = 0.004 for whole body DEXA), w ith no significant change in pulse frequency with increasing obesity ( R = -0.17, P = 0.23 for BMI). In conclusion: 1) the prevalence of gona dotropin abnormalities is very high in women with PCOS selected on pur ely clinical grounds, but is modified by recent spontaneous ovulation; 2) the positive relationship between LH pulse frequency and both pool LH and LH to FSH ratio supports the hypothesis that a rapid frequency of GnRH secretion may play a key etiologic role in the gonadotropin d efect in PCOS patients; 3) pool LH and LII pulse amplitude are inverse ly related to body mass index and percent body fat in a continuous fas hion; and 4) the occurrence of a continuous spectrum of gonadotropin a bnormalities varying with body fat suggests that nonobese and obese pa tients with PCOS do not represent distinct pathophysiologic subsets of this disorder.