Effects of age on hypoxic tolerance in women
Authors: Citherlet Tom , Raberin Antoine , Manferdelli Giorgio , Millet Grégoire 
Published: February 2023

Introduction
The prevalence of acute mountain sickness (AMS) is increasing with altitude (i.e., 10-25% at 2,500 m and 50-85% at ~ 5,000 m; Bärtsch & Swenson, 2013). While there is no error-free test to predict its occurrence, several risk factors and tests have been proposed. For example, the hypoxic ventilatory response (HVR) measures the ratio between the increase in ventilation (VE) and the decrease in pulse saturation (SpO2) during hypoxic exposure. Some studies reported an increased (Lhuissier et al., 2012), no difference (Pokorski and Marczak, 2003), or a decreased HVR (Kronenberg and Drage, 1973) with age. The effect of sex remains also debated since women have been reported to have a higher (Richalet et al., 2012) or lower (Schneider et al. 2002; Vardy et al., 2006) AMS prevalence. Therefore, we aimed to compare measurements of HVR, VE and SpO2 between pre- (PreM) and post-menopausal (postM) women and to investigate if they are related to AMS. We hypothesized differences in hypoxic tolerance between age groups.
Methods
We screened pre-menopausal women (PreM; n = 13; age = 31.7 ± 7.8yr; weight = 63.5 ±9.6 kg; height = 167 ±10 cm) during three phases (early follicular, Fol1; late follicular, Fol2; luteal, Lut3) of their menstrual cycle and post-menopausal women (PostM; n = 15; age = 62.8 ±2.3 yr; weight = 56.1 ±8.3 kg; height 163 ±5 cm) on one occasion. They were evaluated with a pure nitrogen breathing test (N2T; Solaiman et al., 2014) for HVR and with a cycling exercise (5 min of rest followed by 5 min of cycling at 1.5 W/kg) in hypoxia (FiO2 = 14%; simulated altitude of 3,500 m) with measurement of SpO2 and VE. They were then exposed to one night in real altitude (3,375 m) with AMS assessment (Lake Louise Score; Roach et al., 2018).
Results
PreM had a higher resting VE in normoxia (9.95-10.07 vs 8.50 L/min; P < 0.05) and increased VE (7.49-8.78 vs 5.41 L/min; P < 0.05) during the N2T at the three measurements points than PostM. Moreover, only at Fol2, HVR (-0.43 vs -0.27 L/min/%; P = 0.023), VEpeak (18.9 vs 15.0 L/min; P = 0.025) during N2T and resting SpO2 in normoxia (95.9 vs 94.9, P = 0.093) were higher in PreM. The prevalence of AMS was similar between PreM and PostM (30.8 vs 40.0%). When AMS positive and AMS negative subgroups were compared, no difference in HVR was found while there were differences in SpO2 and VE.
Discussion/Conclusion
The main finding of the present study is that HVR was higher in PreM than in PostM only during the late follicular phase of the former. Since estrogen is known to have a stimulatory effect on both pulmonary ventilation and blood vessel vasodilation and peaks during this phase, this suggests that it is the main trigger of the observed differences in HVR. The prevalence of AMS was in line with the literature for a similar altitude (34% at 3,650m; Maggiorini et al., 1990). Contrary to Richalet et al. (2012), HVR did not diagnose AMS in any group nor was lower in the older age group. No other parameter showed to be a solid predictive metric for AMS. Given conflicting results in this study (i.e., HVR and AMS) and in the literature, there is no clear evidence of an effect of age on hypoxic tolerance and on AMS prediction.
References
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