Polycystic ovarian syndrome (PCOS) is a highly prevalent heterogeneous syndrome associated with abdominal obesity, insulin resistance and the metabolic syndrome. This clustering of risk factors could translate into an adverse cardiovascular disease (CVD) risk profile. Endothelial dysfunction, an early barometer of CVD, has been exhibited by women with PCOS; however, it remains unclear whether endothelial dysfunction is independent of CVD risk factors in this population. Exercise training has been found to enhance conduit artery and cutaneous microvessel endothelial function in various populations. Nevertheless, limited research exists regarding the cardiovascular effects of exercise in PCOS, and its impact on endothelial function in conduit arteries and cutaneous microvessels, has not been explored. The primary aim of this thesis was to examine nitric oxide (NO)-mediated endothelial function at different levels of the vascular tree in women with PCOS and to establish whether supervised exercise training induces a therapeutic effect on endothelial function. A systematic review of published studies comparing FMD in PCOS and control women was conducted. Twenty-one published studies were identified for inclusion (pCOS n=908; controls n=566). Differences in FMD between PCOS and controls were synthesised and meta-regressed against BMI and age. The pooled mean FMD was 3.5% lower (95% CI=3.4, 3.7%; P < 0.001) in women with PCOS compared with controls; and the PCOS-mediated reduction in FMD was most evident in studies involving less obese women. PCOS [n=35, 28y (95% CI=26, 30), 31kg/m2 (95% CI=27, 35)] and control women [n=16, 32y (95% CI=30, 35), 30kg/m2 (95% CI=25, 32)] were recruited. Brachial artery endothelial function was assessed using flow-mediated dilation (FMD). Internal adipose tissue (lAT), subcutaneous (SAT), visceral (VAT) and abdominal SAT was quantified using whole body magnetic resonance imaging and IH magnetic resonance spectroscopy quantified liver and skeletal muscle fat. Cardiorespiratory fitness, glycaemic control, reproductive hormone and lipid profiles were also assessed. FMD was impaired in PCOS when compared with control women [-4.5% (95% CI=-6.3, -2.8), P < O.OOl]. When FMD was adjusted for individual differences in IAT [-4.3% (95% CI=-6.l, -2.4), P < O.OOl], VAT [-4.4% (95% CI=-6.3, -2.5), P < O.OOl] and insulin resistance [-3.9% (95% CI=-5.6, -2.1), P < O.OO 1], the difference in FMD between groups remained. Ten women with PCOS [27y (95% CI=23, 32), 31 kg/rrr' (95% CI=28, 34)] completed a 16-week supervised exercise programme while 7 women with PCOS [29y (95% CI=24, 35), 35kg/m2 (95%CI=31, 40)] opted for conventional care and followed simple lifestyle advice. Exercise training improved FMD to a greater degree than conventional care [3.4% (95% CI=1.8, 5.1), P > 0.0005] and in parallel greater improvements in cardiorespiratory fitness were observed with exercise [4.7ml/kg/min (95% CI=1.4, 7.9), P=0.005]. These changes with exercise occurred independently of changes in VAT, SAT or insulin resistance. NO-mediated vasodilation in the cutaneous microvessels was examined in 11 PCOS [29y (95% CI=25, 34), 34kg/m2 (95% CI=30, 38)] and 6 control women [29y (95% CI=21, 37), 34kg/m2 (95% CI=28, 39)] using laser Doppler flowmetry combined with intra-dermal microdialysis of L-NG-monomethyl arginine to assay the NO dilator system in response to incremental local heating of the forearm. Six women with PCOS [30y (95% CI=22, 37), 31kg/m2 (95% CI=25, 37)] then undertook a 16-week exercise-training programme. Nitric oxide contribution was attenuated in women with PCOS at peak heating [-16.0CVCmax (95% CI=-32.5, 0.6), P=0.05] and during prolonged maximal heating [-15.4CVCmax (95% CI=- 29.6, -1.3), P=0.04], compared with control women. Cardiorespiratory fitness improved by 5.0ml/kg/min (95% CI=0.9, 9.2) following exercise training (P=0.03). This was accompanied by increased NO contribution to cutaneous blood flow between 36.5-42°C (P < 0.05), at peak heating [19.6CVCmax (95% CI=4.3, 34.9), P=0.02] and during prolonged maximal heating [17.1CVCmax (95% CI=2.2, 32.2), P=0.03]. The findings from this thesis suggest that endothelial dysfunction is an intrinsic characteristic of PCOS and that supervised exercise training enhances endothelial function in both conduit vessels and cutaneous microvessels, independent of adiposity or traditional CVD risk factors. The direct impact of exercise training on the vasculature of women with PCOS may decrease the risk of CVD morbidities, such as hypertension, and consequently reduce cardiovascular mortality in post-menopausal years.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:570704 |
| Date | January 2012 |
| Creators | Sprung, Victoria Spencer |
| Publisher | Liverpool John Moores University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://researchonline.ljmu.ac.uk/6119/ |
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