The results from the current study showed higher AMS rate in women than in men. The female sex and greater SpO2 reduction after exercise at low altitude prior to the ascent were independently associated with increased risk of AMS. Interestingly, SpO2 reduction at low altitude was associated with the risk of AMS and higher AMS score in men but not in women. Previous studies have estimated that 10–70% of travelers will experience various degrees of AMS when ascending to elevation of 2500m or more. At 4500–5500m, the incidence of AMS in unacclimatized persons has been estimated at 50–85%. In army recruits ascending from sea level to Lhasa by aircraft, AMS incidence has been reported to be 57%. The rate of AMS at 47.5% in the current study is generally consistent with these previous reports. The discrepancy among the studies may reflect differences in a variety of factors, including field conditions, the speed of ascent, arrival altitude, ethnicity of the enrolled study subjects, as well as timing of AMS assessment after the ascent.
Sex differences in AMS have been previously reported, but with inconsistent conclusions. A meta-analysis supported higher susceptibility in women. In the current study, we confirmed higher rate of AMS in women. Notably, 75.0% of the women in the current study developed AMS upon ascent to 4100m. This rate is similar to a study in which 69.2% of women developed AMS. That study also suggested that anxiety at low altitude is an independent predictor of AMS upon ascent, and women tend to have higher levels of anxiety. The fact that anxiety levels are higher in younger adults and women may partly explain the difference in AMS susceptibility between women and men. However, some other studies failed to show a difference in the rate of AMS between men and women, and others even found higher risk of AMS in men. These inconsistent findings may be attributed to ethnic and age differences, different levels of anxiety, history of high altitude exposure, experience with hiking, and prophylactic use of pharmacological agents. In addition, resting cortisol levels at sea level are associated with fluid balance and AMS risk after ascent, suggesting the involvement of the autonomic nervous and endocrine system.
Higher incidence of AMS in women may be explained by the effects of hormones. First, testosterone has potent erythropoiesis action. High serum testosterone and hemoglobin levels are conducive to improvements in oxygen transport, normal cellular function, and thus lower susceptibility to AMS. Second, 17 beta-estradiol could reduce the operating point for osmoregulation of arginine vasopressin and contribute to fluid retention. It could also upregulate the expression of vascular endothelial growth factor (VEGF), which in turn promotes endothelial cellular proliferation, angiogenesis, and vascular permeability. Fluid retention and increased permeability of the vascular endothelium compromise the blood-brain barrier and promote brain tissue swelling and intracranial hypertension.
Under hypoxia, the sympathetic system is activated to ensure a sufficient oxygen supply. Heart rate variability (HRV) is a common indicator that reflects the balance of cardiac autonomic nervous function between the sympathetic system and the parasympathetic system. HRV has been found to be associated with AMS risk; however, the assessment of HRV requires a 12-lead electrocardiogram, and more importantly, the predictive value is limited. A more convenient indicator is needed for the general population under field conditions. A previous study suggested that decreased SpO2 at rest increases the likelihood of AMS upon ascent to high altitude. Fluid accumulation in the pulmonary vasculature and/or inflammatory reactions in the peripheral airways may reduce pulmonary gas exchange under hypoxic conditions. This may further decrease SaO2 and cause hypoxia-induced illness. Exercise testing under hypobaric conditions in the laboratory could identify subjects who will develop severe HAI upon ascent in some but not all studies. Also, such a method is apparently not suitable as a screening test to identify subjects susceptible to the less severe AMS in the general population.
In the current study, SpO2 change after arriving at 4100m was positively correlated with AMS in women. In addition to the effects of hormones, the regulation of the respiratory system and changes in physiological parameters also play important roles in the development of AMS. Relatively smaller tidal volume and higher breathing frequency in women could conceivably lead to increased strain on respiratory muscles under hypoxia and exercise conditions. Women are also more susceptible to hypoxemia, which may explain why the higher incidence of AMS in women was observed in the current and previous studies. We also showed an association between SpO2 change after exercise testing at low altitude with AMS risk in the entire cohort, and more so in men. ΔeSpO2 after exercise testing at low altitude was also positively correlated with AMS score in men, suggesting that ΔeSpO2 after mild exercise could be a useful tool to predict AMS. Subjects with higher maximal oxygen consumption (VO2max) values perform better at endurance exercise. VO2max has been shown to be strongly associated with red cell volume and hemoglobin concentration. Higher VO2max, red cell volume, and hemoglobin concentration as the result of testosterone stimulation may partly explain the low incidence of AMS in men. When subjects exercised at equal intensity, the oxygen consumption in men was more remarkable, and exercise-induced desaturation could predict AMS risk. However, this did not translate into an increased incidence of AMS in men.
Consistent with a meta-analysis study about smoking and AMS, we found a lower percentage of smokers in the AMS group. Smokers have higher basal carbon monoxide (CO), which in turn decreases cerebral blood flow velocities, and thus decreases the risk of high altitude headache and AMS. CO could occupy the binding sites of hemoglobin and decrease the oxygen content in the circulating blood. These mechanisms may explain why smokers are less susceptible to AMS in the current study. In a previous study, smoking was also a protective factor against AMS during acute hypoxia exposure. Such a finding by no means advocates smoking, since smoking could impair long-term acclimatization in addition to causing a variety of serious health problems.
Age has been inversely associated with AMS in some but not all studies. Trekkers younger than 60 years are twice as likely to develop AMS, possibly due to less experience and more rapid ascent. The ratio of cranial cerebrospinal fluid to brain volume increases with age and may serve as a compensatory adaptation to limit the effect of brain swelling and ultimately decrease susceptibility to AMS. Also, respiratory responses to hypoxia and blood oxygenation increase with age in men, and lung diffusion limitation was less prominent in older people. These findings may help to explain the wide difference in exercise-induced desaturation under hypoxic conditions across age groups.
Higher AMS score and lower SaO2 have been found in obese subjects. Such a phenomenon may be partly related to greater SpO2 reduction during the night at high altitude. In the current study, BMI was lower in the AMS group. In addition to BMI, however, other factors (e.g., waist, body fat, and body composition) may also affect the development of AMS. As a result, BMI should not be considered in isolation. For example, the female sex was strongly associated with increased AMS risk. Whether and how AMS susceptibility in women is connected to lower weight and BMI in women requires further studies.
