Ventilatory and heart rate responses to hypoxia in pre‐ and post‐menopausal ethnically Tibetan women residing at ∼3800 m in Mustang, Nepal

Journal article

Humans residing at high altitude exhibit distinct physiological traits, some of which may enhance oxygen transport under conditions of chronic hypoxia. Highlanders exhibit variation in their responses to acute hypoxia, including differences in their hypoxic ventilatory response (HVR) and hypoxic heart rate response (HHRR). Little is known about whether variations in these measurements are influenced by menopausal status. We hypothesized that pre‐menopausal women living at high altitude would exhibit greater HVR and HHRR than their post‐menopausal counterparts. We measured HVR and HHRR in 374 ethnically Tibetan women (46–86 years of age) living in Mustang, Nepal (>3500 m). Pre‐menopausal women had higher oxygen saturation (P < 0.0001) and minute ventilation (P = 0.002) while breathing room air, as well as higher HVR (P < 0.0001) and higher minute ventilation in acute isocapnic hypoxia (P < 0.0001). HR did not differ between groups while breathing room air, but HR (P < 0.0005) and HHRR (P < 0.0001) were higher in pre‐menopausal women during isocapnic hypoxia. HVR and HHRR were associated with higher oxygen saturation in both groups (P < 0.0001) and negatively associated with age only in the post‐menopausal group (P < 0.0001). Genetic analyses revealed genotype–phenotype associations with both end‐tidal carbon dioxide ( P ETC O 2 ${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ) in room air and ventilation during hypoxia. These data suggest ventilatory and heart rate responses to hypoxia wane in Tibetan women residing at high altitude after menopause, when their contributions to reproductive fitness shift from bearing additional children to supporting the survival and care of existing offspring. image Key points: Hypoxic ventilatory (HVR) and heart rate responses (HHRR) vary among high‐altitude Tibetans, but the contribution of menopausal status to this variation has been largely unknown. In 374 Tibetan women living >3500 m in Nepal, pre‐menopausal women had higher oxygen saturation and ventilation at rest and during acute hypoxia than post‐menopausal women, while resting heart rate did not differ by menopausal status. Pre‐menopausal Tibetan women also showed significantly higher minute ventilation and heart rate during isocapnic hypoxia, as well as higher HVR and HHRR. HVR and HHRR positively correlated with oxygen saturation at both life stages but declined with age only in post‐menopausal women. These findings demonstrate that menopause and ageing independently reduce hypoxic cardiorespiratory responses, highlighting life‐stage‐specific physiological adaptation in high‐altitude Tibetan women.

Authors: Moya, EA; Yu, JJ; Craig, SR; Di Rienzo, A; Witonsky, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: The Journal of Physiology
• Article number: JP290648
• Publication date: 2026-06-12
• Acceptance date: 2026-04-27
• DOI: 10.1113/jp290648
• EISSN: 1469-7793
• ISSN: 0022-3751
• Language: English
• Keywords: hypoxic heart rate response; high altitude; Tibetan women; menopause; hypoxic ventilatory response; adaptation; aging; hypoxia