Hoyos, Diana B. Collantes

Background: Hypoxia challenges the regulation of arterial oxygenation (SaO 2 ), eliciting a compensatory increase in ventilation ([Formula: see text]E) to preserve blood-gas homeostasis. However, the ability to maintain blood-gas homeostasis during hypoxic exercise may differ between sexes due to differences in chemoreflex drive and the mechanical capacity to augment ventilation. The purpose of this study was to evaluate sex differences in ventilatory and blood-gas responses to progressive hypoxia during moderate walking exercise. Specifically, we asked whether females would be more susceptible to hypoxemia. We hypothesized that females would exhibit a smaller ventilatory response and a less steep ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) compared with males, resulting in a greater reduction in SaO 2 during progressive hypoxia. Methods: Twenty-six physically active adults (15M: age 35.3±9.4; [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 36.2±9.0; [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) were studies during two visits. Visit 1: we determined the participants’ maximal oxygen uptake ([Formula: see text]O 2 max) during an incremental treadmill test. Visit 2: participants walked at ~50% of their [Formula: see text]O 2 max while we reduced the fraction of inspired oxygen (FiO 2 ) progressively every 5 minutes (0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). Arterial blood samples were collected from a brachial artery catheter during the final 30 seconds of each stage; cardiometabolic and ventilatory data were averaged over the final minute of each stage. The test ended when peripheral oxygen saturation (SpO 2 ) fell below 70%. Because 0.13 FiO 2 was the lowest stage completed by all participants, Δ responses were calculated from 0.21 to 0.13 FiO 2 . Independent t-tests compared Δ responses between sexes; data are mean±SD, significance was set at p < 0.05. Results: There was no significant difference in ΔSaO 2 between sexes across hypoxia (M: −22.0±3.7%; F: −22.8±5.5%; p = 0.89). Males had higher arterial oxygen content (CaO 2 ) than females across all stages (M: 20.6±1.2 to 16.0±1.4 mL O 2 ·dL -1 ; F: 18.5±1.1 to 13.8±2.0 mL O 2 ·dL -1 ), but the ΔCaO 2 during hypoxia was not significantly different between sexes (M: −4.6±0.7; F: −4.7±1.4 mL O 2 ·dL -1 ; p = 0.86). Similarly, there was no significant difference in the change in arterial CO 2 (ΔPaCO 2 ) between sexes (M: −5.8±1.5 mmHg; F: −6.5±3.6 mmHg, p = 0.51). In contrast, males exhibited a significantly greater increase in ventilation (Δ[Formula: see text]E: +13.9±4.2 L·min -1 ) than females (+8.6±2.7 L·min -1 ; p = 0.003). Consequently, the ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) was steeper in males (−2.46±0.66 L·min -1 ·mmHg -1 ) compared with females (−1.57±0.68 L·min -1 ·mmHg -1 ; p = 0.004). However, when Δ[Formula: see text]E was expressed relative to maximal ventilatory capacity (%[Formula: see text]Emax), there was no sex difference (M: 8.8±2.6% vs F: 8.3±2.8%; p = 0.68). Conclusion: Females were not more susceptible to hypoxemia than males; both sexes showed comparable reductions in SaO 2 during moderate exercise in progressive hypoxia. Reductions in PaCO 2 were also similar, indicating comparable ventilatory drive. Although males exhibited a larger absolute increase in [Formula: see text]E and a steeper ventilatory CO 2 -response, this difference disappeared when Δ[Formula: see text]E was expressed relative to %[Formula: see text]Emax. These findings indicate that apparent sex differences in ventilation during hypoxia largely reflect differences in ventilatory capacity rather than true differences in oxygenation or ventilatory drive. Taken together, these findings challenge the assumption that females are inherently more susceptible to hypoxemia or have a lower ventilatory drive than males during moderate hypoxic exercise. Funding: NIH T32 DK007352, UL1 TR002377 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.

Background: During hypoxic exercise, oxygen transport becomes increasingly challenged as oxygen availability decreases. As the inspired oxygen fraction (FiO 2 ) decreases, peripheral oxygen saturation (SpO 2 ) gradually declines, then drops rapidly upon reaching the steepest point of the sigmoidal shaped, oxyhemoglobin dissociation curve. This reduction in FiO 2 creates a distinct SpO 2 “breakpoint,” which likely represents the threshold at which compensatory mechanisms, such as increases in ventilation and cardiac output, can no longer maintain arterial oxygenation. Several physiological factors may modulate this breakpoint, including hemoglobin concentration, blood volume, and ventilatory capacity. This study aimed to determine the SpO 2 breakpoint during steady-state, submaximal, hypoxic exercise and examine whether factors like sex, age, and fitness level influence the SpO 2 breakpoint. We hypothesized that SpO 2 breakpoints would differ by sex, age, and fitness level, with earlier breakpoints visible in females, older adults, and those with higher aerobic fitness. Methods: Twenty-six physically active adults (15M: age 35±9 yrs, [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 38±10 yrs, [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) participated in a two-day study. Day one: participants performed a treadmill [Formula: see text]O 2 max test. Day two: participants walked at a steady state of ~50% of their [Formula: see text]O 2 max, for 40 minutes, while FiO 2 was progressively reduced every 5 minutes in a stepwise fashion (0.25, 0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). The test was terminated when SpO 2 dropped below 70%. SpO 2 was measured continuously using a clinical-grade oximeter. Analysis was performed in RStudio by first determining each participant’s individual SpO 2 vs time breakpoint. Male and Female breakpoints were compared to assess sex-based differences. To evaluate whether SpO 2 breakpoint timing differed by age or fitness level, participants were then divided into tertiles for each variable. Age tertiles were derived from the sample distribution of chronological age, and fitness tertiles were defined using [Formula: see text]O 2 max (L/min). Mean breakpoint times were compared between the highest and lowest tertiles for both age and fitness. Mean SpO 2 breakpoints were compared between groups using independent sample t-tests. Significance was set to p< 0.05. Results: The overall mean breakpoint occurred at an SpO 2 of 90.7±2.8% during the 0.17 FiO 2 stage. No significant sex differences were observed in breakpoint SpO 2 and timing (M: SpO 2 = 90.7±2.7%, time = 18.6 min; F: SpO 2 = 90.7±3.0%, time = 17.7 min; p = 0.961). Age did not significantly influence breakpoint (younger tertile [21-30 yrs] SpO 2 = 91.0±2.4%, time = 18.4 min; older tertile [41-60 yrs] SpO 2 = 91.1±2.4%, time = 17.2 min, p = 0.953). Additionally, fitness level showed no significant difference on breakpoint (low fitness [1.91-3.01 L/min]: SpO 2 = 90.3±3.1%, time = 17.8 min; high fitness [4.38-5.25 L/min]: SpO 2 = 90.4±2.9%, time = 19.2 min; p = 0.992). Conclusion: During a hypoxic, steady state walking exercise, at ~50% [Formula: see text]O 2 max, we observed no difference in the peripheral oxygen saturation breakpoint, across sex, age, and fitness level. This may suggest that moderate exercise in hypoxia does not sufficiently challenge the cardiopulmonary system for individual variations in oxygen transport to influence the breakpoint. These findings imply that the SpO 2 breakpoint, during hypoxic exercise, may represent a physiological marker of the upper limit for maintaining oxygen saturation in healthy adults. Applying this protocol to identify SpO 2 breakpoints may offer insights for improving pharmacological interventions and our understanding of clinical populations with impaired oxygen transport. 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.

Abstract Females likely experience larger performance benefits from androgenic‐anabolic steroids than males. We set out to determine if there were temporal differences in select athletics (track and field) records between females and males. Exploratory aims included: (1) evaluating the improvements in female and male world records over time, and (2) investigating the influence of doping programs on male and female world records before and after 1990, when sports governing bodies began to implement random out‐of‐competition and systematic in‐competition drug testing. We collected the top 500 performances of all time for both sexes from an online database (worldathletics.org) in four running events (100, 200, 400 and 800 m) and two throwing events (discus throw and shot‐put). Data were stratified into quintiles based on world record ranking (1st to 100th, 101st to 200th, etc.). The temporal distribution of the top 100 female performers was significantly earlier than the top 100 male performers (year: 2000 ± 1 vs. 2005 ± 1, respectively; P < 0.0001). Within the event, the top performances occurred significantly earlier for females in the 800 m (year: 1995 ± 15 vs. 2003 ± 12; P = 0.0007) and shot‐put (year: 1992 ± 14 vs. 2003 ± 17; P = 0.0004). Among females, world records rapidly improved through the 1980s, but following 1990, the world records ceased to improve. Geographically, there was a greater representation of countries with state‐sponsored doping programs, specifically among female performances. We postulate these sex differences in the temporal distribution of top performances are likely associated with enhanced effectiveness of exogenous androgens (steroid doping) among female athletes with lower endogenous androgen hormones compared to males.