Polycystic Ovarian Syndrome as a State of Premature Ageing of the Nitric Oxide System

Abstract

Ageing per se represents an independent risk factor for ischaemic heart disease, but the mechanism(s) underlying this effect remains controversial. Polycystic ovarian syndrome (PCOS) appears to engender premature development of heart disease, irrespective of comorbidities. We have now evaluated the impact of ageing and menopause on vascular and platelet nitric oxide (NO) signalling in normal women aged 18–60 years, and compared these changes with an age-matched group of PCOS subjects. Methods: We evaluated platelet responsiveness to NO via whole blood aggregometry, vascular endothelial function and NO responsiveness using applanation tonometry, and utilised asymmetric dimethylarginine (ADMA) concentrations as an index of endogenous inhibition of NO generation. Results: In normal women (n = 132), platelet NO responsiveness (ANOVA, F = 9.9, p < 0.0001) and vascular endothelial function (F = 7.7, p < 0.0001) decreased whilst ADMA increased significantly (F = 6.4, p = 0.0005) with age. Detailed evaluation of 40 perimenopausal women revealed no correlation between plasma oestradiol levels and changes in NO response. In PCOS subjects (n = 109) there was no significant fluctuation of NO response (F = 1.9, p = 0.1), vascular endothelial function (F = 0.6, p = 0.6) or ADMA (F = 1.6, p = 0.2) with age. However, NO response and vascular endothelial function were impaired (2 way ANOVA, F = 4.2, p = 0.04 and F = 5.6, p = 0.02 respectively) and ADMA was elevated (F = 47.0, p < 0.0001) relative to normal women, with these anomalies already evident in women <40 years. Vascular NO responsiveness showed identical differences for both age and PCOS. Conclusions: (1) Normal female ageing is associated with progressive impairment of platelet/vascular NO signalling, (2) in PCOS subjects, similar changes are already present in young adults.