Association between serum concentrations of nitric oxide and transition to menopause

Abstract

Objective Menopausal status may increase cardiovascular disease (CVD) risk. Nitric oxide plays a role in the protection against CVD onset and progression but has not been studied around the time of menopause. We investigated associations between serum nitric-oxide metabolite (NOx) concentrations and menopausal status. Design Comparative case-control cross-sectional study. Setting Tehran Lipid and Glucose Study, university center. Sample Sub-groups from a cohort of 2137 women, of whom 213 met enrollment criteria. Methods We studied four sub-groups in a 1.2 ratio: (1) post-menopausal women (n = 29) with natural amenorrhea for 13-24 months, (2) age- and BMI-matched controls (n = 58) with regular menstrual cycles; (3) peri-menopausal women (n = 42) with natural amenorrhea for 1-12 months, and (4) age- and BMI-matched women as controls for the last group of women (n = 84). Main outcome measure Serum nitric oxide concentrations. Results Medians (inter-quartile ranges) of NOx in post-menopausal women and their controls were 31 (21.7-40.2) and 23.5 (17.2-31) μmol/L, respectively (p = 0.012). In peri-menopausal women and their controls the medians (inter-quartile ranges) were 28 μmol/L (18.5-50.5) and 25 (20-31.25) μmol/L, respectively (p = 0.035), but were not significantly different between peri- and postmenopausal women and were unchanged after adjustment for lipids. In a conditional fixed-effect logistic regression model, the risk of "transition to menopause" and "menopause" rose respectively 2.44- and 2.27-fold for a one-score increase in the NOx standard deviation. Conclusion Menopausal status, by itself and not as a consequence of aging, is associated with increased serum nitric oxide concentrations. Identification of variables associated with menopausal cardiovascular consequences may be used to improve women's health after menopause.