Exploring potential sex differences in cerebral blood flow responses to hyperoxia

Background: Hyperoxia, oxygen-enriched inhalation, is used in clinical settings to support impaired cerebral oxygenation, like traumatic brain injury. However, hyperoxia can paradoxically reduce cerebral blood flow (CBF); prior studies showed decreases up to 37%, potentially due to increases in reactive oxygen species (ROS) that trigger vasoconstriction. Although higher estrogen levels are associated with lower ROS and may partly explain higher cerebral perfusion in females, the underlying mechanisms are poorly understood. Therefore, we hypothesized females would exhibit less hyperoxia-induced reductions in CBF than males. Methods: 19 healthy young adults (8F and 11M; age (yrs) = 23 ± 6 F, 22 ± 4 M; BMI (kg/m 2 ) = 22 ± 2 F, 23 ± 2 M; P all > 0.05) participated. Female were tested on days 1-5 of menstrual cycle. CBF was measured by pseudo-continuous arterial spin labeling (pcASL) MRI at whole brain and grey matter (GM) levels during normoxia, followed by scans at 5 (H1), 10 (H2), 25 (H3), and 30 minutes (H4) after the onset of ~90% inspired O 2 . Heart rate (HR), mean arterial pressure (MAP), and end-tidal CO 2 (ETCO 2 ) were recorded. Results: HR did not differ significantly between sexes at any time (P all > 0.05). Females had lower MAP during NO (78 ± 5 F vs 86 ± 6 mmHg M, P 0.05). ETCO 2 did not differ by sex at any time point (P > 0.05); despite efforts to clamp, there was a 1 mmHg increase during H1-H4 from rest (P 0.05). Also, relative reduction in GM did not differ between sexes at H1 (-14 ± 10% F, -10 ± 19% M), H2 (-19 ± 10% F, -17 ± 17% M), H3 (-20 ± 13% F, -24 ± 16% M), or H4 (-22 ± 8% F, -20 ± 17% M) (P all > 0.05). Similarly, although hyperoxia decreased cerebral oxygen delivery (CDO 2 ) in females and males, there were no sex differences in relative reductions across any hyperoxic time points (-4 ± 13% F vs 3 ± 13% M at H1; -8 ± 14% F vs -4 ± 14% M at H2; -9 ± 14% F vs -10 ± 15% M at H3; -12 ± 10% F vs -16 ± 33% M at H4; P all > 0.05). Discussion: Contrary to our hypothesis, both sexes exhibited similar reductions in CBF across all hyperoxic time points. While hyperoxia elicited robust reductions in CBF in both sexes, females consistently maintained higher cerebral perfusion. Similarly, hyperoxia-induced reductions in CDO 2 did not differ between sexes, suggesting that despite higher baseline perfusion, females experience proportional declines comparable to males. This suggests that hyperoxia may exert a uniformly constrictive and oxygen‐delivery–reducing effect across sexes, requiring the need for caution when administering oxygen therapy. Future studies should examine potential variations across menstrual cycle and incorporate mechanistic approaches to further elucidate sex-specific responses. This abstract was presented at the American Physiology Summit 2026 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.