Metformin Reduces Arterial Stiffness and Improves Endothelial Function in Young Women with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled, Crossover Trial

Context: Patients with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance and display subclinical evidence of early cardiovascular disease. Metformin improves insulin sensitivity and circulating markers of cardiovascular risk in patients with PCOS, but it is unclear whether this translates into improvements in vascular function. Objective: Our objective was to evaluate the effects of metformin on arterial stiffness and endothelial function in women with PCOS. Design and Intervention: Thirty women with PCOS were assigned to consecutive 12-wk treatment periods of metformin or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout. Main Outcome Measures: The primary outcome measures were assessments of arterial stiffness [augmentation index (AIx), central blood pressure, and brachial and aortic pulse wave velocity (PWV)] and endothelial function. Anthropometry, testosterone, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high-sensitivity C-reactive protein, adiponectin, and plasminogen activator inhibitor-1) were also assessed. Results: Metformin improved AIx [-6.1%; 95% confidence interval (CI) for the difference -8.5 to -3.5%; P < 0.001], aortic PWV (-0.76 m/sec; 95% CI for the difference -1.12 to -0.4 m/sec; P < 0.001), brachial PWV (-0.73 m/sec; 95% CI for the difference -1.09 to -0.38; P < 0.001), central blood pressure (P < 0.001), and endothelium-dependent (AIx after albuterol; P = 0.003) and endothelium-independent (AIx after nitroglycerin; P < 0.001) vascular responses. Metformin also reduced weight (P < 0.001), waist circumference (P < 0.001), and triglycerides (P = 0.004) and increased adiponectin (P = 0.001) but did not affect testosterone or other metabolic measures. Conclusions: Short-term metformin therapy improves arterial stiffness and endothelial function in young women with PCOS. (J Clin Endocrinol Metab 95: 722-730, 2010)