Current concepts in the polycystic ovary syndrome.
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.
Dunaif
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Division of Women's Health, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. adunaif@partners.org
Thomas
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D000728:Androgens / Q000502:physiology; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006062:Gonadotropins / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D009017:Morbidity; D010375:Pedigree; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D015995:Prevalence; D011972:Receptor, Insulin / Q000235:genetics; D012307:Risk Factors
D000728:Androgens; D008078:Cholesterol, LDL; D006062:Gonadotropins; D011972:Receptor, Insulin