Ventilatory Response to Hypoxia and Tolerance to High Altitude in Women: Influence of Menstrual Cycle, Oral Contraception, and Menopause

Introduction: Tolerance to high altitude in women might be influenced by hormonal status since female hormones modulate ventilation. Methods: Our objectives were (i) to explore in 1060 women, the influence of the phase of menstrual cycle, oral contraception, and menopause with or without hormonal treatment, on hypoxic ventilatory response at exercise (HVRe) and hypoxic cardiac response at exercise (HCRe) measured during a routine hypoxia exercise test, before an exposure to high altitude; (ii) to determine in 260 women exposed to high altitude, the influence of menopause and oral contraceptive and other drug use, on the prevalence of severe acute mountain sickness (sAMS). Four groups were defined: premenopausal with or without oral contraception and postmenopausal with or without hormonal treatment. Results: In premenopausal women without contraception, HVRe was higher in the early luteal/midluteal phase than in the early follicular phase (0.89 ± 0.37 vs. 0.75 ± 0.27 mL/[min · kg], p = 0.03). HVRe was similar in postmenopausal versus premenopausal women. HCRe was lower in postmenopausal women (p < 0.001), due to aging. HVRe decreased from second to fourth decade of age and increased from fourth to eighth decade, while HCRe consistently decreased with aging. Oral contraception or hormonal treatment had no effect on responses to hypoxia. The prevalence of sAMS was similar in all groups. Severe high-altitude illness score was higher and HVRe lower in women with sAMS. Conclusion: (i) physiological responses to hypoxic exercise depend on the ovarian cycle phase and menopause status, (ii) oral contraception and hormonal treatment have no influence on the tolerance to high altitude, and (iii) independent of hormonal status, aging modulates physiological responses to hypoxia.