Purpose Menopause results in decreased ovarian hormones, potentially impacting physiological responses to hypoxia and its tolerance. This study explored menopause’s influence on physiological responses during rest and exercise in normobaric hypoxia and its role in predicting acute mountain sickness (AMS). Methods Thirteen eumenorrheic women in their mid-luteal phase (EW, age = 32 ± 8 year) and fifteen postmenopausal women (PW, age = 63 ± 2 year) were examined on two occasions. Their ovarian hormonal levels were measured. In the first visit, hypoxic ventilatory response (HVR), physiological responses (ventilation, pulse oximetry, and heart rate) at rest and exercise in normobaric hypoxia (FiO2 = 0.14) and anxiety levels were tested. On the second visit, cortisol awakening response and oxidative stress markers were measured at low altitude, with cortisol awakening response repeated during an overnight stay at high altitude (3375 m) along with evaluation for AMS using the Lake Louise Score, peripheral oxygen saturation and anxiety levels. Results PW exhibited lower estradiol (16.9 ± 16.7 vs 4.6 ± 2.3 pg/ml, p textless 0.01) and progesterone (13.39 ± 7.61 vs 0.06 ± 0.07 ng/ml, p textless 0.001) levels than EW. Despite higher ventilation at rest in EW compared to PW in normoxia (10.0 ± 1.5 vs 8.5 ± 0.9 L/min; p textless 0.01) and hypoxia (9.4 ± 1.3 vs 8.2 ± 1.3 L/min) , HVR (– 0.34 ± 0.13 vs – 0.27 ± 0.15 L/min/%) was similar between groups (p = 0.26). AMS incidence did not differ between EW (31%) and PW (40%). Conclusion In conclusion, EW had higher ventilation at rest in normoxia and normobaric hypoxia compared to PW, but similar responses and AMS incidence at high altitude. Age has minimal impact on HVR in women.