High Altitude Medicine & Biology

Women who use hormonal contraception (HC) may have questions about their use during travel to high altitude. This scoping review summarizes current evidence on the efficacy and safety of HC and cycle control during high-altitude travel.

We performed a scoping review for the International Climbing and Mountaineering Federation (UIAA) Medical Commission series on Women’s Health in the Mountains. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including contraception) with additional publications found by hand search.

We identified 17 studies from 7,165 potentially eligible articles. No articles assessed the efficacy of contraception during a short-term high-altitude sojourn. Current data show no advantage or disadvantage in HC users for acclimatization or acute mountain sickness (AMS). Use of HC during high-altitude travel is common and safe for menses suppression. A potential concern of estrogen-containing HC is the increased thrombotic risk, which theoretically could be compounded in hypobaric hypoxia.

Evidence is limited for the interaction of HC and high altitude on performance, thrombosis, and contraceptive efficacy. HC does not affect the risk of AMS. The most efficacious and safest method at high altitude is generally the one women are most familiar with and already using.

Although some variables related to oxygen transport and utilization such as ventilation, pulmonary vascular responses to hypoxia, heart rate (HR), cardiac output, hemoglobin (Hb), and oxygen saturation (SpO₂) are used to compare adaptation to altitude between populations, peak oxygen consumption (VO₂) constitutes an integrative measure of total oxygen transport that may reflect successful adaptation to altitude. We designed this study to make a direct comparison of VO₂ in a cardiopulmonary exercise test (CPET) between chronic obstructive pulmonary disease (COPD) patients residing at high altitude (Bogotá, Colombia: 2,640 m) (COPD-HA) and those living at low altitude (Bucaramanga, Colombia: 959 m) (COPD-LA).

All patients performed a CPET with measurements of VO₂, minute ventilation (V_E), HR, oxygen pulse (VO₂/HR), ventilatory equivalents (V_E/VCO₂), and SpO₂. Unpaired T-test or Mann–Whitney U test were used for comparisons between COPD-HA and COPD-LA.

We included 71 patients with COPD, 53 COPD-HA, and 18 COPD-LA. There were no differences between groups in age, sex, or forced expiratory volume in 1 second. The means ± SD of Hb, g/dl was slightly higher in COPD-HA (15.9 ± 1.9 vs. 14.7 ± 1.8, p = 0.048), without differences in VO₂, % pred (71.6 ± 17.9 vs. 69.0 ± 17.0, p = 0.584), VO₂/HR, % pred (92.1 ± 22.0 vs. 89.7 ± 19.8, p = 0.733) or V_E/MVV, % (75.5 ± 14.1 vs. 76.5 ± 14.3, p = 0.790) at peak exercise between groups. Median (IQR) of V_E/VCO₂ nadir [38.0 (37.0–42.0) vs. 32.5 (31.0–39.0), p = 0.005] was significantly higher, and SpO₂, % at rest [88.0 (86.0–91.0) vs. 95.0 (94.0–96.0), p < 0.001] and at peak exercise [84.0 (77.0–90.0) vs. 93.0 (92.0–95.0), p < 0.001] were significantly lower in COPD-HA.

Despite higher desaturation at rest and during exercise in COPD-HA, there were no differences in VO₂ peak between COPD-HA and COPD-LA, suggesting a potential altitude adaptation in those patients chronically exposed to hypoxia.

Exercising in hypoxia may confer multiple health benefits, but the evidence for specific benefits is scarce.

We investigated effects of intermittent hypoxic training (IHT) on the quality of life and functional fitness of healthy adult women, in a double-blind, randomized, placebo-controlled study. Subjects performed 36 sessions of IHT (experimental group, n = 41; fraction of inspired oxygen [FIO₂]: 0.17) or the same training in normoxia (control group, n = 41; FIO₂: 0.21). Health-related quality of life, fitness tests, and hemoglobin levels were assessed before (T1), directly after (T2), and 4 weeks after (T3) cessation.

At T2, upper body strength (+14.96%), lower body strength (+26.20%), and agility (−4.94%) increased significantly in the experimental group compared to baseline but not in controls. The experimental group improved lower body strength more (by 9.85%) than controls at T2 and performed significantly better in walking (by 2.92%) and upper body strength testing (by 16.03%), and agility (by 4.54%) at T3. Perceived general health and vitality was significantly greater in the experimental group at T2 and T3 compared with T1. None of these improvements were observed in the control group.

IHT is a promising strategy to induce long-lasting fitness benefits in healthy adult women.

The regulation of noncoding ribonucleic acid (ncRNA) has been shown to be involved in cellular and molecular responses to hypoxic preconditioning (HPC), a situation created by the induction of sublethal hypoxia in the brain. The ncRNAs metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and nuclear paraspeckle assembly transcript 1 (NEAT1) are abundantly expressed in the brain, where they regulate the expression of various genes in nerve cells. However, the exact roles of MALAT1 and NEAT1 in HPC are not fully understood.

A mouse model of acute repeated hypoxia was used as a model of HPC, and MALAT1 and NEAT1 levels in the hippocampus were measured using real-time polymerase chain reaction (PCR). The mRNA and protein levels of N-methyl-d-aspartate receptor subunit 2 B (NR2B) in the mouse hippocampus were measured using real-time PCR and western blotting, respectively. HT22 cells knocked-down for MALAT1 and NEAT1 were used for in vitro testing. Expression of NR2B, which is involved in nerve cell injury under ischemic and hypoxic conditions, was also evaluated. The levels of spectrin and cleaved caspase-3 in MALAT1 and NEAT1 knockdown HT22 cells under oxygen glucose deprivation/reperfusion (OGD/R) were determined by western blotting.

HPC increased the expression of MALAT1 and NEAT1 and decreased the expression of NR2B mRNA in the mouse hippocampus (p < 0.05). Knockdown of MALAT1 and NEAT1 increased both NR2B mRNA and protein levels nearly twofold and caused damage under OGD/R conditions in HT22 cells (p < 0.05).

MALAT1 and NEAT1 exert neuroprotective effects by influencing the expression of NR2B.

Homicides are a major public health concern and a leading cause of preventable deaths worldwide. The relationship between altitude and homicides remains unclear, and evidence of the possible effects of living at high altitudes on homicide rates is limited. This research aimed to investigate the mortality rates resulting from various types of aggression that culminated in homicides in Ecuador and to explore potential differences associated with altitude.

An ecological analysis of homicide rates in Ecuador was conducted from 2001 to 2022. Homicide cases and the population at risk were categorized based on their place of residence according to two altitude classifications: a binary classification of low (<2,500 m) and high altitude (>2,500 m), and a detailed classification according to criteria by the International Society for Mountain Medicine, which includes low (<1,500 m), moderate (1,500–2,500 m), high (2,500–3,500 m), and very high altitude (3,500–5,500 m) categories. Both crude and directly age–sex standardized mortality rates were calculated for each altitude category.

We analyzed a total of 40,708 deaths attributed to aggressions (ICD-10 codes X85–Y09). The total homicide rate for men was 21.29 per 100,000 (95% confidence interval [CI]: 9.55–32.37), whereas for women, it was 2.46 per 100,000 (95% CI: 1.44–3.27). Average rates across the 22 analyzed years were higher at low altitudes (men: 13.2/100,000 and women: 1.33/100,000) as compared with high altitudes (men: 5.79/100,000 and women: 1.05/100,000). Notably, the male-to-female rate difference was more pronounced at low altitudes (898%) than at high altitudes (451%).

Our study revealed a higher prevalence of homicides in certain provinces and significant disparities in mortality rates between men and women. Although we cannot establish a direct relationship between altitude and homicide rates, further research is needed to explore potential confounding factors and a better understanding of the underlying causes for these variations.

Hypoxia at high altitudes results in elevated uric acid (UA) and reduced estimated glomerular filtration rate (eGFR). However, the impact of a prolonged high-altitude sojourn on UA levels and renal function in patients with preexisting hyperuricemia warrants further exploration. The study was to investigate the eGFR and related factors in patients with preexisting hyperuricemia following exposure to high altitude.

The study included 345 participants, who worked at a high altitude for 1 year. Anthropometric and laboratory indices were collected before ascent (i.e., baseline), as well as 20 and 80 days after descent. The participants were categorized into individuals with hyperuricemia (HUA) or normal uric acid (NUA) group based on the presence or absence of hyperuricemia at baseline.

No difference in baseline eGFR was observed between the two groups before ascend or on day 20 after descent (p > 0.05). However, on day 80, eGFR of the HUA group was lower compared with the NUA group (p < 0.05). Correlations existed between post-descent eGFR levels and variables, including sampling time, UA levels, total and direct bilirubin, and baseline grouping.

After high-altitude exposure, the recovery of eGFR was delayed in participants with preexisting hyperuricemia. Preexisting hyperuricemia and high-altitude hypoxia jointly contribute to renal impairment.

Decreased oxygen saturation and exercise tolerance are commonly experienced at high altitude. Continuous positive airway pressure (CPAP) devices have become increasingly portable and battery powered, providing a potentially unique new therapeutic modality for treatment of altitude-related illnesses. This study evaluated the potential use of CPAP devices to improve and maintain oxygen saturation at altitude, both at rest and with exertion, to evaluate the feasibility of using this device at altitude.

Subjects were taken to Mount Blue Sky and monitored while they hiked to the summit (4,350 m), maintaining a consistent level of exertion. Subjects hiked for 0.7 km both with and without CPAP set to 10 cmH₂O pressure. Continuous vital signs were collected during the hike and recovery period.

All subjects completed the hike wearing CPAP devices at a vigorous level of exertion. Mean oxygen saturation of the CPAP group (M = 83.8%, SD = 3.72) was significantly higher than that of the control group during exertion (M = 78.7%, SD = 2.97); p = 0.005. Recovery after exertion was quicker in the CPAP group than the control group. Three subjects experienced claustrophobia requiring a brief pause, but were able to complete their exercise trial without removing equipment or experiencing adverse events. When pauses from claustrophobia were excluded, there was no difference in completion time between the groups (p = 0.06).

CPAP reliably improved oxygen saturation at rest and during vigorous exertion at high altitude. Its ability to correct hypoxemia, even with physical exertion, may prove useful after further study as a portable self-carried device to prevent and treat altitude-related illness, or to improve safety in high-altitude rescues.