Cutaneous Microvascular Endothelial Function: Effects of Sex and Menopause Stage

Abstract

BackgroundEndothelial dysfunction and increased arterial stiffness are both associated with increased risk of cardiovascular events and mortality.Vascular aging has been characterized by deteriorating endothelial function accompanied by increasing vascular stiffness that occurs with increasing chronological age, with the onset of these changes varying by sex. Deteriorating large artery vascular function has been reported across the menopause transition in women, but it is unclear if this relationship extends to the cutaneous microvasculature, which may have critical implications for both thermal regulation and general cardiovascular health.Purpose & HypothesisThe primary purpose of this study was to determine the impact of sex and menopausal stage on cutaneous endothelial dependent (EDD) vasodilation. We hypothesized that cutaneous EDD vasodilation would decrease in women in a graded manner across the transition from pre, to peri, to postmenopause with differences compared to age matched men. Secondly, we hypothesized that there would be no differences in cutaneous EDD vasodilation between natural and surgical (i.e., hysterectomy) menopause.MethodsPremenopausal, (n=8, 44±5y), perimenopausal (n=6, 51±2y), and postmenopausal women (n=9, 60±7y) as well as men age matched to the postmenopausal group (n=6, 59±7y) volunteered for this study. Cutaneous EDD vasodilation was measured by local iontophoresis of Acetylcholine (Ach) administration into the forearm vasculature. Red blood cell flux was determined by laser Doppler flowmetry at baseline and after 200µL of Ach. CVC was calculated as the quotient of red blood cell flux and mean arterial pressure and expressed as the percentage increased from baseline (CVC%). Differences were determined using a 1‐way ANOVA. Data are presented as mean ± standard error.ResultsForearm microvascular CVC% was significantly different among groups (P=0.01) after Ach administration. Post hoc analyses revealed an attenuated CVC% response in postmenopausal women (691±150%; P=0.02) and men (733±127%; P=0.05) compared to premenopausal women (1398±247%). There were no differences detected between peri‐ and premenopausal women (1290±140% vs. 1398±247%; P=0.95). Further, we performed a subanalysis in our postmenopausal group which included surgical (n=3) and natural (n=8) postmenopausal women. No differences were present between surgical and natural postmenopausal women (P=0.87), while both the surgical (646±163%; P=0.08) and natural (713±221%; P=0.05) postmenopausal women appeared to have decreased CVC responses compared to premenopausal women (1398±247%).ConclusionsOur findings indicate that cutaneous EDD vasodilation decreases from pre‐ to postmenopause in healthy women. Our data suggests that decreases in microvascular function agrees with reported decrements in large vessel vascular function associated with the menopause transition.