Endocrine Abstracts

Background Polycystic ovary syndrome (PCOS) affects between 5-10% of premenopausal women and is characterised by insulin resistance. PCOS also carries with it an increased lifetime risk of diabetes, hypertension and possibly coronary heart disease. The underlying mechanisms are unknown but we have proposed that metabolic insulin resistance may be associated with endothelial dysfunction, leading to increased vascular stiffness, abnormalities of fibrinolysis and increased platelet aggregation. Methods We measured in 31 women (19 PCOS, 15 control): (i) pulse wave velocity (PWV) (ii) markers of haemostasis (iii) insulin sensitivity (iv) platelet aggregation. Control subjects were matched for BMI. For the aggregation studies, the effect of insulin on a concentration response curve (CRC) to ADP was carried out by performing a CRC at baseline and during the hyperinsulinaemic clamp. Results The PCOS group had a higher brachial PWV (9.08 vs. 8.27 ms-1, p =0.03). t-PA concentration was significantly (age-adjusted p=0.013) elevated in women with PCOS. T-PA correlated with BMI in both PCOS and controls (r= 0.428, p<0.01 and r= 0.686, p<0.01) and inversely with M/I (r= -0.590 p<0.05 and r= -0.620, p<0.05, respectively. There was also a significant difference between the PCOS group vs. control group for the change in the ADP EC50 following insulin incubation. (126±38.5 vs. 164±19 % respectively, p=0.032). This change correlated inversely with brachial PWV (r=-0.568, p=0.034). Conclusion Women with PCOS exhibit increased large artery stiffness, a defect that correlates with abnormalities of insulin action on platelet aggregation. They also exhibit elevated t-PA levels, a marker shown to correlate both with the severity of coronary artery disease at angiography and independently with CHD event rate. Thus, increased vascular stiffness, abnormal fibrinolysis and platelet aggregation, in a group of young women with PCOS, may help explain the increased prevalence of hypertension and cardiovascular disease seen in later years.