Polycystic ovary syndrome is associated with endothelial dysfunction

Background-We recently reported endothelial dysfunction as a novel cardiova scular risk factor associated with insulin resistance/obesity. Here, we tes ted whether hyperandrogenic insulin-resistant women with polycystic ovary s yndrome (PCOS) who are at increased risk of macrovascular disease display i mpaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteri stics. Methods and Results-We studied leg blood flow (LBF) responses to graded int rafemoral artery infusions of the endothelium-dependent vasodilator methach oline chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women w ith PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group (P<0.01). Euglycemic hyperinsulinemia increased LBF above bas eline by 30% in the PCOS and 60% in OBW group (P<0.05 between groups), Acro ss all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels (r=-0.52, P<0.007). This relatio nship was stronger than with any other parameter, including insulin sensiti vity. Conclusions-PCOS is characterized by (1) endothelial dysfunction and (2) re sistance to the vasodilating action of insulin. This endothelial dysfunctio n appears to be associated with both elevated androgen levels and insulin r esistance. Given the central vasoprotective role of endothelium, these find ings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.