Session: 604 APS Sex differences in physiological responses to exercise/environmental stressors Poster Session
(604.1) Hypoxic Vasodilation is Augmented During the High versus Low Estrogen Phase of the Menstrual and Oral Hormonal Contraceptive Pill Cycle
Sunday, April 3, 2022
10:15 AM – 12:15 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E468
Dain Jacob (University of Missouri), Jennifer Harper (University of Missouri), Clayton Ivie (University of Missouri), Jacqueline Limberg (University of Missouri)
Presenting Author University of Missouri Columbia, Missouri
Background: Hypoxia elicits peripheral vasodilation to preserve oxygen delivery to metabolically active tissue. Hypoxic vasodilation, predominantly mediated by β-adrenergic and nitric oxide mechanisms, is greater in adult female participants compared to adult male participants. Greater circulating estrogen in adult females has been purported to contribute to observed sex differences in hypoxic vasodilation. Nearly 80% of adult females in the United States will take oral hormonal contraceptive pills (OCPs) in their lifetime. Adult females taking OCPs exhibit greater β-adrenergic receptor mediated vasodilation and nitric oxide production relative adult females with natural menstrual cycles (NC). Strategically utilizing the fluctuations of circulating estrogen that occur within a NC and OCP cycle, we aimed to examine the contribution of endogenous and exogenous estrogen on hypoxic vasodilation in female participants. We hypothesized female participants taking OCPs would exhibit greater hypoxic vasodilation relative to female participants with a NC. We further hypothesized hypoxic vasodilation would be greatest during the high estrogen (HE) phase of the menstrual or pill cycle compared to the low estrogen (LE) phase.
Methods: Ten female participants with a NC (25±1 yrs, 23±1 kg/m2) and ten female participants taking monophasic OCPs (24±1 yrs, 21±1 kg/m2) completed two study visits (IRB #2011312, NCT03606434). Participants were studied once during the LE phase of the menstrual or pill cycle (Cycle day: NC 3±1; OCP 5±1) and once during the HE phase of the menstrual or pill cycle (Cycle day: NC 15±1; OCP: 17±1). Forearm blood flow (venous occlusion plethysmography) and blood pressure (BP, finger plethysmography) were measured during normoxia and hypoxia (80% SpO2). Blood flow was normalized for BP and expressed as forearm vascular conductance (FVC).
Results: Hypoxia elicited an increase in FVC (% change from baseline) that was greater during the HE phase (NC: 21±10%, OCP: 41±6%) of the menstrual/pill cycle compared to the LE phase (NC: 5±8%, OCP: 10±8%) in both NC and OCP participants (Main effect of phase, plt;0.01; Main effect of group, p=0.16; Interaction of phase and group, p=0.30).
Conclusion: Hypoxic vasodilation is augmented in the HE phase of the menstrual and pill cycle in healthy young female participants, independent of whether the hormone is endogenous (NC) or exogenous (OCP). These data further our understanding of the role of estrogen in hypoxic vasodilation. These findings may have clinical implications for the vascular response to hypoxia in conditions of low estrogen (i.e., postmenopause) and/or estrogen excess, and warrant further investigation.