Popliteal flow-mediated dilatory responses to an acute bout of prolonged sitting between earlier and later phases of natural menstrual and oral contraceptive pill cycles

Abstract

Uninterrupted sitting can impair popliteal flow-mediated dilation (FMD) responses in young, premenopausal females when endogenous or exogenous estrogen levels are low. However, it is unknown if sitting-induced FMD responses are altered when estrogen levels are elevated in females who naturally menstruate (NAT) or those using combined, monophasic oral-contraceptive-pills (OCP). This study tested the hypothesis that the decline in popliteal FMD following an acute bout of prolonged sitting would be attenuated during the later versus earlier phases of a natural menstrual or OCP cycle. Popliteal FMD was measured before and after 3-h of sitting in NAT-females (n=9; 23±3 years) and OCP-females (n=9; 23±3 years) during both of their respective phases. At pre-sit, relative FMD was greater in the later phase versus earlier phase in NAT (4.6±1.6% to 5.8±1.5%; P=0.002), but not between pill phases among OCP (4.4±1.2% to 4.8±1.6%; P=0.32). Both groups exhibited similar prolonged sitting-induced impairments in popliteal FMD (Pre-Post Sitting Time: P<0.001; Group ΔFMD: P=0.66; Phase ΔFMD: P=0.42; Interaction ΔFMD: P=0.72), regardless of menstrual cycle phase (earlier: -2.5±1.5%; later: -2.4±1.0%) or pill phase (inactive-pill: -2.4±1.4%; active-pill: -2.1±1.1%). Our findings demonstrate that lower-limb arterial endothelial-dependent vasodilatory function was enhanced in the later versus earlier menstrual phase among NAT, but unaffected by combined, monophasic pill phases in OCP. Furthermore, healthy, young females exhibited pronounced negative lower-limb vascular effects in response to prolonged sitting regardless of whether they were in the earlier or later phases of a natural menstrual or contraceptive pill cycle.

Vascular Responses to Passive and Active Movement in Premenopausal Females: Comparisons across Sex and Menstrual Cycle Phase

“…Cardiovascular disease risk is consistently reported to be lower in premenopausal females (PMF) when compared with their male counterparts and postmenopausal women (1), with speculation that this lower CVD risk may derive in part from the direct and indirect benefits of the sex hormone estrogen (E2-estradiol) on peripheral vascular function. This speculation is supported in prior research that highlighted significant improvements in vascular function during the phase of the menstrual cycle where circulating estrogen levels are typically highest (e.g., late follicular [LF] vs early follicular [EF] phase) (2–7). In contrast, current research in PMF using more standardized vascular assessments and menstrual cycle phase methodology have identified similar, or lower (8), vascular function when compared with age-matched men (9,10), as well as no intraindividual differences across menstrual cycle phases (8,11,12).…”

“…The sex hormone estrogen, specifically 17β-estradiol, E2, has numerous proposed genomic and nongenomic effects on vascular function and blood flow regulation, such as the upregulation of NO bioavailability via direct NO production or augmented scavenging of factors that can neutralize NO and other vasoactive components (reactive oxygen-nitrogen species). Thus, to minimize fluctuations in macrovascular and microvascular function observed throughout the menstrual cycle that had previously been reported (2–7), prior studies evaluated vascular function in the EF phase when circulating sex hormone (e.g., estrogen, progesterone) levels are lowest. Interestingly, recent literature in this area now suggests limited alterations to vascular function across menstrual cycle phases (8,11,12), with a recent meta-analysis and systematic review indicating a “very low” impact of menstrual cycle phase on both macrovascular and microvascular function (17).…”

Sex comparisons in physiological and cognitive performance during hypoxic challenge

“…Increased report of headache during hypoxia for females is particularly relevant in an aeromedical context because headache frequency is a major factor influencing suitability for aviation service ( Hesselbrock and Haynes, 2020 ). Hormonal contraceptive use is related to cerebrovascular and cognitive changes, which could be further altered during hypoxic conditions; future works should explore the association between hormonal contraceptive use and headache reports ( O’Brien et al, 2020 ; Theunissen et al, 2022 ). The risk of migraine recurrence is also an important factor for aeromedical readiness, particularly in pilot applicants who incur a substantial training investment.…”

Impact of habitual sedentary patterns on popliteal artery endothelial-dependent vasodilation in healthy adults

“… 4 , 16 , 17 Measures of popliteal blood flow, SR, shear rate area under curve (SR AUC ), and absolute and relative FMD were determined using standardized calculations. 18 – 20 The statistical assumptions required to conduct allometric scaling or SR AUC -normalization of FMD were not met. Specifically, the regression between relative FMD (β = 8.33E −5 , 95% CI = 1.81E −5 , 14.85 −5 ; y-intercept = 3.566, 95% CI = 2.821, 4.311) and absolute FMD (β = 4.19E −6 , 95% CI = −0.01E −6 , 8.38E −6 ; y-intercept = 0.175, 95% CI = 0.175, 0.271), with SR AUC did not have an intercept of zero.…”