Sex comparison of hypoxic cerebral vasodilation: Do sex hormones matter?

Background: Postmenopausal women have a higher risk of developing cardiovascular diseases compared to men and premenopausal women; a phenomenon possibly attributed to declining sex hormones. Postmenopausal women are more prone to stressors like hypoxia and susceptible to severe complications. This study investigated how sex hormones and biological sex affect cerebral blood flow (CBF) responses to hypoxia. We tested the hypotheses: 1) females exhibit greater hypoxic cerebrovascular reactivity, 2) suppression of endogenous sex hormones abolish reactivity differences, and 3) sex differences in hypoxic reactivity are magnified with returning only a single sex hormone (estrogen in females, testosterone in males). Methods: 12 healthy young subjects (5 males, 7 females; age 24±4 yr, BMI 22±2) were non-obese, normotensive, and free of cardiovascular disease. Exclusions included smoking and females on hormonal birth control or currently pregnant. The study involved three MRI visits: (1) baseline (BL), (2) after hormone suppression (HS) for 5-6 days taking oral gonadotropin releasing hormone Orilissa (plus aromatase inhibitor Anastrozole in males), (3) followed by continued Orilissa with addition of single sex hormone (Single Hormone Add-Back: SHAB; testosterone for males, estradiol for females). Female participants conducted BL scans on days 1-7 of their menstrual cycle. On study days participants avoided exercise, nonsteroidal anti-inflammatory drugs, and caffeine for 24 hours and fasted for >8 hours. The MRI protocol included pseudo-continuous Arterial Spin Labeling scans for cerebral blood flow (CBF) measurements under both room air and hypoxia conditions to decrease oxygen saturation (SpO 2 pulse oximetry) to 80-85% while maintaining normocapnia. Hypoxic reactivity was calculated as ΔCBF/ΔSpO 2 from normoxia to hypoxia. Results: Hypoxia decreased arterial content of oxygen and increased CBF (main effect, p<0.002). Contrary to our hypothesis, hypoxic vascular reactivity was not different between sexes (main effect, p=0.295) or across HS or SHAB (interaction effect, p=0.790). Interestingly, grey matter cerebral O 2 delivery was reduced in HS (main effect, p<0.047) and SHAB (main effect, p<0.0023). Conclusion: These data suggest that both sexes can maintain CBF challenges to hypoxia vasodilation despite changes in hormonal levels. Reduced grey matter cerebral O 2 delivery under HS and SHAB may hold implications for understanding the stability of brain function during hypoxia under conditions of cardiovascular or neurologic disease which are often associated with hormonal shifts. Funding NIH (R01 HL150361) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.