Women at Altitude: Sex-Related Physiological Responses to Exercise in Hypoxia

Abstract

Sex differences in physiological responses to various stressors, including exercise, have been well documented. However, the specific impact of these differences on exposure to hypoxia, both at rest and during exercise, has remained underexplored. Many studies on the physiological responses to hypoxia have either excluded women or included only a limited number without analyzing sex-related differences. To address this gap, this comprehensive review conducted an extensive literature search to examine changes in physiological functions related to oxygen transport and consumption in hypoxic conditions. The review encompasses various aspects, including ventilatory responses, cardiovascular adjustments, hematological alterations, muscle metabolism shifts, and autonomic function modifications. Furthermore, it delves into the influence of sex hormones, which evolve throughout life, encompassing considerations related to the menstrual cycle and menopause. Among these physiological functions, the ventilatory response to exercise emerges as one of the most sex-sensitive factors that may modify reactions to hypoxia. While no significant sex-based differences were observed in cardiac hemodynamic changes during hypoxia, there is evidence of greater vascular reactivity in women, particularly at rest or when combined with exercise. Consequently, a diffusive mechanism appears to be implicated in sex-related variations in responses to hypoxia. Despite well-established sex disparities in hematological parameters, both acute and chronic hematological responses to hypoxia do not seem to differ significantly between sexes. However, it is important to note that these responses are sensitive to fluctuations in sex hormones, and further investigation is needed to elucidate the impact of the menstrual cycle and menopause on physiological responses to hypoxia.

Fig. 1

Schematic representation of altitude-related changes in convective (calculated from V̇O₂ = cardiac output × difference in arterio-venous O₂ content, sigmoid line, [236]) and diffusive (calculated from V̇O₂ = diffusion coefficient × mixed venous O₂ pressure, straight line, [236]) components of V̇O_2max in one male and female individual matched for sea-level V̇O_2max. The full line is in normoxia, the dotted line is in hypoxia (5260 m). The individual datasets are from [237]. Cardiac output was computed with pulse wave contouring analysis. The convective component was reduced to a larger extent in female individual due to a higher altitude-induced hypoxemia and lower hemoglobin concentration, while no clear differences in cardiac hemodynamic responses were noted. Due to a higher compensatory vasodilation and lower sympathetic vasoconstrictor activity, the diffusive component of V̇O_2max was improved in female individuals in hypoxia. Therefore, female individuals seem more centrally but less peripherally limited than men when exercising in hypoxia. V̇O₂ oxygen uptake, PO₂ oxygen pressure

Fig. 2

Schematic representation of estrogen (blue curve) and progesterone (red curve) expected in eumenorrheic women and their potential influence on altitude-related physiological responses. The transition from follicular to luteal phase is determined by ovulation. The gray half circles represent each phase and the black line illustrates the schematic representation of the hormonal environment (related to the sum of estrogens and progesterone). HVRe hypoxic ventilatory response at exercise, SaO₂ oxygen arterial saturation

Fig. 3

Mechanisms of sex-related differences in response to hypoxia. HVR hypoxic ventilatory response, SaO₂ oxygen saturation, BP blood pressure, HR heart rate. References: Lung and airway volume [37, 38, 44], Ventilatory constraints [22, 23, 33], Exercise-induced hypoxemia [27, 28, 33], BP and HR during exercise [–59], Microvascular responses to occlusion and exercise [122, 127], Muscle composition [130], Substrate preferences in endurance exercise [129]