Hormonal status and reproductive life-course states as modulators of women's physiological responses to acute and chronic hypoxia: insights, challenges, and perspectives.

Hypoxia research has significantly advanced our understanding of how the human body responds to low-oxygen environments, yet women are still frequently studied without adequate consideration of hormonal status or reproductive life-course stage. This review examines the complex interactions between hormonal status across the female life course and the specific physiological responses of women to acute and chronic hypoxia, focusing on the menstrual cycle, hormonal contraception, pregnancy, menopausal status, hormone replacement therapy, gender-affirming hormone therapy, and reproductive health in high-altitude environments. Estrogen and progesterone significantly modulate ventilatory, cardiovascular, hematological, vascular, and muscular/metabolic responses to hypoxia, with distinct effects across different menstrual cycle phases, contraceptive regimens, and life-course states. Menopause introduces additional complexities, as declining hormone levels alter the body's ability to acclimatize to low-oxygen conditions. Additionally, we examine how chronic and lifelong hypoxia impacts reproductive health, including fertility and pregnancy outcomes, in women living at high altitudes, highlighting both physiological adaptations and contextual factors. While current research has made progress, further studies are needed to better understand these sex-specific responses. We propose that future research should integrate stratified approaches, accounting for hormonal status (cycle phase, contraceptive use, pregnancy, HRT, GAHT) and reproductive status, to optimize health and performance recommendations for women exposed to hypoxic environments.