Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome

OBJECTIVE - We aimed to determine the impact of medical therapy for symptom management on insulin resistance, metabolic profiles, and surrogate markers of cardiovascular disease in polycystic ovary syndrome (PCOS), an insulin-resistant pre-diabetes condition. RESEARCH DESIGN AND METHODS - One hundred over-weight women (BMI > 27 kg/m(2)), average age 31 years, who were nonsmokers, were not pregnant, did not have diabetes, and were off relevant medications for 3 months completed this 6-month open-label controlled trial. Randomization was to a control group (higher-dose oral contraceptive [OCP] 35 mu g ethinyl estradiol [EE]/2 mg cyproterone acetate, metformin [1 g b.d.] or low-dose OCP [20 mu g EE/100 mu g levonorgestrel + aldactone 50 ing b.d.]). Primary outcome measures were insulin resistance (area under curve on oral glucose tolerance test) and surrogate markers of cardiovascular disease including arterial stiffness (pulse wave velocity [PWV]) and endothelial function. RESULTS - All treatments similarly and significantly improved symptoms including hirsutism and menstrual cycle length. Insulin resistance was improved by metformin and worsened by the high-dose OCP. Arterial stiffness worsened in the higher-dose OCP group (PWV 7.46 vs. 8.03 m/s, P < 0.05), related primarily to the increased insulin resistance. CONCLUSIONS - in overweight women with PCOS, metformin and low- and high-dose OCP preparations have similar efficacy but differential effects on insulin resistance and arterial function. These findings suggest that a low-dose OCP preparation may be preferable if contraception is needed and that metformin should be considered for symptomatic management, particularly in women with additional metabolic and cardiovascular risk factors.