Cardiometabolic aspects of the polycystic ovary syndrome

[Truncated abstract] Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk factors including insulin resistance, hypertension, dyslipidaemia and obesity. Despite this, prospective long-term studies demonstrating an increased prevalence of cardiovascular events in this population are lacking. There has been a resultant increase in studies of surrogate markers of cardiometabolic risk in the setting of PCOS in order to more accurately predict the risk of future vascular events in these women. This thesis tests the principal hypothesis that PCOS is associated with cardiometabolic risk, and that this risk is modifiable. The aim of the thesis was firstly to investigate the prevalence of cardiovascular risk factors such as the metabolic syndrome (MetS), endothelial dysfunction, and arterial stiffness in PCOS, and examine relationships between metabolic characteristics of PCOS and markers of cardiovascular risk. Secondly, this thesis aimed to examine the effects of omega-3 fatty acids on liver fat and other cardiometabolic risk factors in women with PCOS. Four observation statements were derived from the principal hypothesis and tested with the studies described below. Study 1 investigated the prevalence of the MetS in PCOS by three definitions - World Health Organisation (WHO), National Cholesterol Education Program Adult Treatment Panel 3 (NCEP-ATP-III), and International Diabetes Federation (IDF) - compared with the background population. This was a cross-sectional study of 168 women with PCOS and 883 age matched controls. The prevalence of the MetS in PCOS subjects was 33% by WHO, 37% by NCEP-ATP-III, and 40% by IDF criteria, compared with 10% by NCEP-ATP-III and 13% by IDF in controls (p30 kg/m2), the prevalence of MetS was significantly higher among those with PCOS (p=0.027). Dehydroepiandrosterone sulfate was associated with a lower risk of the MetS, (OR 0.86, 95% CI 0.77-0.97, p=0.011). Study 2 investigated endothelial function and arterial stiffness in women with PCOS and is presented in two parts. Firstly, a cross-sectional case-control study was undertaken of 19 young non-obese women with PCOS, and 19 healthy controls (part A). Endothelial function was assessed with flow mediated dilatation (FMD) of the brachial artery, while arterial stiffness was assessed with pulse wave velocity (PWV) and augmentation index (AI). While there were no significant differences between PCOS vi and control subjects when assessing blood pressure, insulin resistance, lipids, or oestradiol, women with PCOS had higher free androgen index scores (5.14 (3.47) vs. 3.25 (1.42), p=0.036). PCOS subjects had significantly lower FMD compared with controls (6.5 (2.9) vs. 10.5 (4.0) %, p