Dunaif A, Mandeli J, Fluhr H, Dobrjansky A
Department of Medicine, Mt. Sinai School of Medicine, City University of New York, New York 10029.
J Clin Endocrinol Metab. 1988 Jan;66(1):131-9. doi: 10.1210/jcem-66-1-131.
We investigated whether obesity was a marker for a neuroendocrinologically distinct form of the polycystic ovary syndrome (PCO). Further, since women with PCO have significantly higher basal and/or glucose-stimulated plasma insulin levels, we also examined the effects of chronic hyperinsulinemia on gonadotropin and gonadal steroid secretion. Ten obese women (nine with acanthosis nigricans) and five nonobese women (one with acanthosis nigricans) with PCO as well as seven obese and six nonobese women of comparable age and weight in the midfollicular phase of their cycles were studied. Pulsatile gonadotropin release was determined for 6-24 h as well as gonadotroph sensitivity to GnRH (10 micrograms, iv). The obese PCO women had significantly increased basal and glucose-stimulated plasma insulin levels compared to the other groups, the nonobese PCO and the obese normal women had similar insulin levels, and the nonobese normal women had the lowest insulin levels. All four groups had similar plasma estradiol levels. Both the obese and the nonobese PCO women had similar and significantly higher mean plasma LH levels, LH pulse amplitude, and integrated LH responses to GnRH compared to values in both normal groups (P less than 0.01 to P less than 0.001); the obese PCO women did not differ from the nonobese PCO women. The mean LH pulse frequencies per 6 h were similar in the four groups. FSH secretion did not differ significantly in the four groups. The levels of the putative gonadal feedback steroids, plasma total and non-sex hormone-binding globulin-bound testosterone, non-sex hormone-binding globulin-bound estradiol, and estrone, were similar in both PCO groups and were significantly higher than those in both normal groups (all P less than 0.001). The only independent effect of obesity was on plasma androstenedione levels and the androstenedione to estrone ratio, both of which were significantly higher in PCO women than normal women (P less than 0.01 to P less than 0.001), but significantly lower in the obese (PCO and normal) women than in nonobese (PCO and normal) women (P less than 0.05). These findings suggest that 1) the impact, if any, of obesity in PCO is not reflected in discernible changes in gonadotropin release or in the gonadal steroid feedback environment; and 2) insulin does not have a major role in the perpetuation of PCO, since obese and nonobese PCO women had similar reproductive hormone levels despite significantly different degrees of hyperinsulinemia.
我们研究了肥胖是否是多囊卵巢综合征（PCO）一种神经内分泌学上独特形式的标志物。此外，由于患有PCO的女性基础和/或葡萄糖刺激后的血浆胰岛素水平显著更高，我们还研究了慢性高胰岛素血症对促性腺激素和性腺类固醇分泌的影响。研究了10名肥胖女性（9名有黑棘皮症）和5名非肥胖女性（1名有黑棘皮症），她们患有PCO，同时还研究了7名肥胖和6名非肥胖、年龄和体重相当且处于月经周期卵泡中期的女性。测定了6 - 24小时的促性腺激素脉冲式释放以及促性腺激素对GnRH（10微克，静脉注射）的敏感性。与其他组相比，肥胖的PCO女性基础和葡萄糖刺激后的血浆胰岛素水平显著升高，非肥胖的PCO女性和肥胖的正常女性胰岛素水平相似，而非肥胖的正常女性胰岛素水平最低。所有四组的血浆雌二醇水平相似。与两个正常组的值相比，肥胖和非肥胖的PCO女性的平均血浆LH水平、LH脉冲幅度以及对GnRH的LH综合反应均相似且显著更高（P小于0.01至P小于0.001）；肥胖的PCO女性与非肥胖的PCO女性没有差异。四组每6小时的平均LH脉冲频率相似。四组中FSH分泌没有显著差异。在两个PCO组中，假定的性腺反馈类固醇、血浆总睾酮和非性激素结合球蛋白结合的睾酮、非性激素结合球蛋白结合的雌二醇和雌酮水平相似，且显著高于两个正常组（所有P均小于0.001）。肥胖的唯一独立影响是对血浆雄烯二酮水平以及雄烯二酮与雌酮的比值，这两者在PCO女性中均显著高于正常女性（P小于0.01至P小于0.001），但在肥胖（PCO和正常）女性中显著低于非肥胖（PCO和正常）女性（P小于0.05）。这些发现表明：1）肥胖对PCO的影响（如果有的话）并未体现在促性腺激素释放或性腺类固醇反馈环境的明显变化中；2）胰岛素在PCO的持续存在中没有主要作用，因为肥胖和非肥胖的PCO女性尽管高胰岛素血症程度显著不同，但生殖激素水平相似。
