Lakhani, K.; (2005) Arterial wall mechanics in women with polycystic ovary syndrome. Doctoral thesis , University of London.

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Abstract

Around 20% women of reproductive age are found to have polycystic ovaries (PCO) during ultrasound examinations and approximately 10% have symptoms of polycystic ovary syndrome (PCOS), which is associated with multiple risk factors for cardiovascular disease. The aim of this thesis was to investigate arterial mechanical properties and responsiveness to vasoactive stimuli in young women with PCOS, PCO and controls, using non-invasive ultrasound techniques. The influence of PCOS-related endocrine and metabolic perturbations on aortic function was investigated in a mifepristone-treated rat model of PCOS. The carotid artery pulsatility index was decreased in PCO and PCOS women and there was a paradoxical vasoconstrictor response to a dilator stimulus in these women relative to controls. Vascular compliance was decreased in the internal carotid artery in PCO and PCOS women PCOS women also exhibited increased intima-media thickness (IMT) of the common carotid and common femoral arteries compared with controls. In the cutaneous microcirculation, the response to the vasodilator acetylcholine (ACh) was depressed in PCOS women, whilst the response to sodium nitroprusside (SNP nitric oxide donor - NO) was unaffected. Mifepristone-treated rats exhibited increased serum luteinising hormone, testosterone, and polycystic ovaries. Ultrasound analysis indicated that aortic diameter and blood flow in vivo were unaffected in treated rats, but aortic compliance was reduced. In-vitro assessment of endothelial and vascular smooth muscle function of rat aorta demonstrated decreased relaxation with ACh, which was not abolished by L-NAME, however, the effect of SNP was greater, a finding which raises the possibility of an alternative dilator mechanism that may be independent of NO system. Since increased IMT, endothelial dysfunction and abnormal reactivity are independent risk factors for cardiovascular disease, these results also provide evidence of preclinical atherosclerotic surrogate markers in women with PCOS and PCO. These findings increase the likelihood of an association between PCOS (and probably PCO) and cardiovascular morbidity and mortality.

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