This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. The clinical presentation of these patients includes infertility, irregular menses, obesity and hirsutism. Hyperinsulinemia and insulin-resistance is thought to play a critical role in the pathogenesis of this condition and contributes to the risk of developing type 2 diabetes mellitus (DM), hypertension and an atherogenic lipid profile. Hyperinsulinemia - insulin resistance is also known to be associated with endothelial dysfunction. Several studies have estimated the PCOS patients are at a four to five fold increased risk for development of complications of coronary and cerebrovascular atherosclerosis. Insulin-sensitizing agents like metformin with or without ovulation inducing agent - clomiphene have been shown to promote ovulation and restore menstrual regularity in these patients. Recent data indicate that metformin reverses endothelial dysfunction in patients with type 2 DM. However, the potential for these drugs to ameliorate endothelial dysfunction and the elevated cardiovascular risk in women with PCOS has not been systematically evaluated. These investigators hypothesize that women with PCOS have underlying endothelial dysfunction and that insulin-sensitizing agents like metformin can potentially reverse endothelial dysfunction in this patient population. They are investigating the in vivo effects of PCOS on both conduit and resistance vessel endothelial function, and thereafter study the effects of metformin treatment on vascular function in this cohort of patients.
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