Menstrual and oral contraceptive pill cycles minimally influence vascular function and associated cellular regulation in premenopausal females.

Abstract

Historical exclusion of females in research has been, in part, due to the perceived influence of natural menstrual (NAT) and oral contraceptive pill (OCP) cycles on vascular outcomes. NAT and OCP cycle phases may influence brachial artery (BA) endothelial function, however, findings are mixed. Minimal research has examined arterial stiffness, smooth muscle and lower limb endothelial function. The purpose of this study was to investigate the influence of NAT and OCP cycles on cardiovascular outcomes and cellular regulation. Forty-nine premenopausal females (n=17 NAT, n=17 2nd generation OCP, n=15 3rd generation OCP) participated in two randomized order visits in the low (LH: early follicular/placebo) and high (HH: mid-luteal/active) hormone cycle phases. BA and femoral artery (SFA) endothelial function [flow-mediated dilation (FMD) test], smooth muscle function (nitroglycerine-mediated dilation test) and carotid and peripheral (pulse wave velocity) arterial stiffness were assessed. Cultured female human endothelial cells were exposed to participant serum for 24h to examine endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERα) protein content. BA FMD was elevated in the HH versus LH phase, regardless of group (HH:7.7±3.5%, LH:7.0±3.3%, p=0.02); however, allometric scaling for baseline diameter resulted in no phase effect (HH:7.6±2.6%, LH:7.1±2.6%, p=0.052, d=0.35). SFA FMD, BA and SFA smooth muscle function, arterial stiffness, and eNOS and ERα protein content were unaffected. NAT and OCP phases examined have minimal influence on vascular outcomes and ERα-eNOS pathway, apart from a small effect on BA endothelial function partially explained by differences in baseline artery diameter.