Thierry van Dessel H J, Lee P D, Faessen G, Fauser B C, Giudice L C
Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1999 Sep;84(9):3030-5. doi: 10.1210/jcem.84.9.5941.
Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We investigated this hypothesis in fasting serum samples from 140 women with PCOS (age, 27.4 +/- 0.4 yr; body mass index, 26.3 +/- 0.5 kg/m2; mean +/- SEM). IGF-related parameters were also studied in a group of normoovulatory women (n = 26; age, 26 +/- 4 yr; body mass index, 23.6 +/- 4.3 kg/m2). For the PCOS group, the mean testosterone (T) level was 2.5 +/- 0.1 nmol/L, and it was significantly correlated with LH (r = 0.41; P < 10(-6)), estrone (r = 0.33; P = 0.016), estradiol (r = 0.18; P = 0.04), and androstenedione (AD; P < 10(-6)), but not with dehydroepiandrosterone sulfate (P = 0.71), a marker of adrenal steroidogenesis. T and AD were also related to total ovarian follicle number and ovarian size, as previously found with normoovulatory women (1). There were no differences between the PCOS subjects and the normoovulatory group for total IGF-I, IGF-II, or IGF-binding protein-3 (IGFBP-3). However, IGFBP-1 levels were significantly decreased in the PCOS group (1.0 +/- 0.2 vs. 7.3 +/- 1.1 ng/mL; P < 0.001) and were inversely correlated with serum insulin levels (r = -0.50; P < 10(-8)). Serum levels of free IGF-I (fIGF-I) were elevated (5.9 +/- 0.3 vs. 2.7 +/- 0.3 ng/mL; P < 0.001) in inverse relation with IGFBP-1 (r = -0.31; P = 0.046). Serum fIGF-I levels were related to total follicle number (r = - 0.35; P < 10(-4)) and to the ratio of sex hormone-binding globulin to T (r = -0.23; P = 0.009). However, these relationships were not independent of other variables. Despite the more than 2-fold elevation in fIGF-I levels, significant relationships between fIGF-I and markers of ovarian steroidogenesis (T, AD, estradiol, and estrone) could not be demonstrated. In conclusion, although we confirmed correlations between LH and hyperandrogenemia and have found abnormalities in the IGF system in a large cohort of PCOS subjects, a direct relationship between hyperandrogenism and the IGF system could not be shown. Previous studies suggest that elevated LH and hyperinsulinemia lead to excess ovarian androgen synthesis in PCOS and that the intraovarian IGF system is important for normal follicle development and may be important in the arrested state of follicle development in PCOS. However, the data presented in this cross-sectional study suggest that insulin-related changes in circulating IGFBP-1 and subsequent elevation of fIGF-I reflect insulin resistance and have little enhancing effects on ovarian steroidogenesis in this disorder.
多囊卵巢综合征（PCOS）是女性无排卵最常见的原因。既往研究表明，PCOS的发病机制可能涉及胰岛素样生长因子（IGF）和卵巢甾体激素生成系统的相关异常。我们在140例PCOS女性（年龄27.4±0.4岁；体重指数26.3±0.5kg/m²；均值±标准误）的空腹血清样本中对这一假说进行了研究。还在一组排卵正常的女性（n = 26；年龄26±4岁；体重指数23.6±4.3kg/m²）中研究了IGF相关参数。对于PCOS组，平均睾酮（T）水平为2.5±0.1nmol/L，且与促黄体生成素（LH）显著相关（r = 0.41；P < 10⁻⁶）、雌酮（r = 0.33；P = 0.016）、雌二醇（r = 0.18；P = 0.04）和雄烯二酮（AD；P < 10⁻⁶），但与硫酸脱氢表雄酮无关（P = 0.71），硫酸脱氢表雄酮是肾上腺甾体激素生成标志物。T和AD也与卵巢卵泡总数和卵巢大小有关，如既往在排卵正常女性中所发现的那样（1）。PCOS受试者与排卵正常组在总IGF-I、IGF-II或IGF结合蛋白-3（IGFBP-3）方面无差异。然而，PCOS组的IGFBP-1水平显著降低（1.0±0.2对7.3±1.1ng/mL；P < 0.001），且与血清胰岛素水平呈负相关（r = -0.50；P < 10⁻⁸）。游离IGF-I（fIGF-I）血清水平升高（5.9±0.3对2.7±0.3ng/mL；P < 0.001），与IGFBP-1呈负相关（r = -0.31；P = 0.046）。血清fIGF-I水平与卵泡总数（r = - 0.35；P < 10⁻⁴）以及性激素结合球蛋白与T的比值（r = -0.23；P = 0.009）有关。然而，这些关系并非独立于其他变量。尽管fIGF-I水平升高超过2倍，但未能证明fIGF-I与卵巢甾体激素生成标志物（T、AD、雌二醇和雌酮）之间存在显著关系。总之，虽然我们证实了LH与高雄激素血症之间的相关性，并在一大群PCOS受试者中发现了IGF系统异常，但未能显示高雄激素血症与IGF系统之间存在直接关系。既往研究表明，LH升高和高胰岛素血症导致PCOS患者卵巢雄激素合成过多，且卵巢内IGF系统对正常卵泡发育很重要，在PCOS卵泡发育停滞状态中可能也很重要。然而，这项横断面研究中的数据表明，循环中IGFBP-1与胰岛素相关的变化以及随后fIGF-I的升高反映了胰岛素抵抗，对该疾病的卵巢甾体激素生成几乎没有增强作用。
