Brachial artery endothelial function is stable across a menstrual and oral contraceptive pill cycle but lower in premenopausal women than in age-matched men

Sex hormone concentrations differ between men, premenopausal women with natural menstrual cycles (NAT), and premenopausal women using oral contraceptive pills (OCP), as well as across menstrual or OCP phases. This study sought to investigate how differences in sex hormones, particularly estradiol, between men and women and across cycle phases might influence brachial artery endothelial function. Fifty-three healthy adults (22 ± 3 yr, 20 men, 15 NAT women, and 18 second-, third-, or fourth-generation OCP women) underwent assessments of sex hormones and endothelial [flow-mediated dilation (FMD) test] and smooth muscle [nitroglycerin (NTG) test] function. Men were tested three times at 1-wk intervals, and women were tested three times throughout a single menstrual or OCP cycle (NAT: menstrual, midfollicular, and luteal phases and OCP: placebo/no pill, “early”, and “late” active pill phases). Endogenous estradiol concentration was comparable between men and women in their NAT menstrual or OCP placebo phase ( P = 0.36) but increased throughout a NAT cycle ( P < 0.001). Allometrically scaled FMD did not change across a NAT or OCP cycle but was lower in both groups of women than in men ( P = 0.005), whereas scaled NTG was lower only in NAT women ( P = 0.001). Changes in estradiol across a NAT cycle were not associated with changes in relative FMD ( r2 = 0.01, P = 0.62) or NTG ( r2 = 0.09, P = 0.13). Duration of OCP use was negatively associated with the average relative FMD for second-generation OCP users only ( r = −0.65, P = 0.04). Our findings suggest that brachial endothelial function is unaffected by cyclic hormonal changes in premenopausal women but may be negatively impacted by longer-term use of second-generation OCPs. NEW & NOTEWORTHY We demonstrate that brachial artery flow-mediated dilation does not change across a menstrual or oral contraceptive pill cycle in premenopausal women but is lower in women than in men. Although unaffected by within-cycle changes in estradiol, brachial flow-mediated dilation is negatively correlated with duration of oral contraceptive pill use for second-generation pills. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/behind-the-bench-episode-2/ .