Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy

Objective: To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome. Design: Randomized controlled trial. Setting: Controlled clinical study. Patient(s): Overweight age- and body mass index-matched women with polycystic ovary syndrome. Intervention(s): Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 mu g ethinyl E-2-2 ma cytoproterone acetate, n = 30). Main Outcome Measure(s): Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism. Result(s): The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL). Conclusion(s): In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear. (Fertil Steril(R) 2010;93:184-91. (C)2010 by American Society for Reproductive Medicine.)