Dunaif A, Thomas A
Division of Women's Health, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
Annu Rev Med. 2001;52:401-19. doi: 10.1146/annurev.med.52.1.401.
Over the past 20 years, it has been clearly documented that the polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and that insulin resistance plays an important role in the pathogenesis of the reproductive disturbances of the disorder. Family studies have indicated a genetic susceptibility to PCOS. Polycystic ovaries and hyperandrogenemia are present in approximately 50% of sisters of affected women. Increased androgen secretion and insulin resistance persist in cultured theca cells and skin fibroblasts, respectively, from women with PCOS; this finding suggests that these are intrinsic, presumably genetic, defects. Insulin resistance and elevated low-density lipoprotein (LDL) levels also cluster in the sisters of women with PCOS, consistent with genetic traits. Moreover, the brothers of women with PCOS have insulin resistance and elevated dehydroepiandrosterone sulfate (DHEAS) levels, which supports a genetic basis for these findings. Family-based studies of linkage and association have implicated several genes in the pathogenesis of PCOS. The strongest evidence to date points to a gene in the region of the insulin receptor. Insulin-sensitizing therapy mitigates the reproductive disturbances of PCOS.
在过去20年中，已有明确记录表明多囊卵巢综合征（PCOS）存在与胰岛素抵抗相关的主要代谢后遗症，且胰岛素抵抗在该疾病生殖功能紊乱的发病机制中起重要作用。家族研究表明PCOS存在遗传易感性。患病女性约50%的姐妹存在多囊卵巢和高雄激素血症。分别来自PCOS女性的培养卵泡膜细胞和皮肤成纤维细胞中，雄激素分泌增加和胰岛素抵抗持续存在；这一发现表明这些是内在的、可能是遗传的缺陷。胰岛素抵抗和低密度脂蛋白（LDL）水平升高在PCOS女性的姐妹中也聚集在一起，这与遗传特征一致。此外，PCOS女性的兄弟存在胰岛素抵抗和硫酸脱氢表雄酮（DHEAS）水平升高，这支持了这些发现的遗传基础。基于家族的连锁和关联研究表明，有几个基因与PCOS的发病机制有关。迄今为止最有力的证据指向胰岛素受体区域的一个基因。胰岛素增敏治疗可减轻PCOS的生殖功能紊乱。
