Sexual (and gender)-dimorphism in tolerance to hypobaric hypoxia increasingly matters for a differential surveillance of human activities at high altitude (HA). At low altitudes, the prevalence of anxiety and depression in women has already been found to double when compared with men; it could be expected to even increase on exposure to HA. In purposefully caring for the health of women at HA, the present work explores the potential involvement of the tryptophan (Trp)–melatonin axis in mood changes on exposure to hypobaric hypoxia. The present work highlights some already known anxiogenic effects of HA exposure. Hypoxia and insomnia reduce serotonin (5-HT) availability; the latter defect being expressed as failure of brown adipose tissue (BAT) activation and mood disorders. Rapid eye movement (REM) sleep organization and synapsis restoration that are additionally affected by hypoxia impair memory consolidation. Affective complaints may thus surge, evolving into anxiety and depression. Sex-related differences in neural network organization and hormonal changes during the menstrual cycle, and certainly also during the life cycle, underscore the possibility of 5-HT–related mood alterations, particularly in women on HA exposure. The mean brain rate of 5-HT synthesis at sea level is already 1.5-fold higher in males than in females. sexual dimorphism also evidences the overexpression effects of SERT, a 5-HT transporter protein. Gonadal and thyroid hormones, as influenced by HA exposure, further modulate 5-HT availability and its effects in women. Besides caring for adequate oxygenation and maintenance of one’s body core temperature, special precautions concerning women sojourning at HA should include close observations of hormonal cycles and, perhaps, also trials with targeted antidepressants.

High altitude (HA) exposure may affect human health and performance by involving the body timing system. Daily variations of melatonin may disrupt by HA exposure, thereby possibly affecting its relations with a metabolic parameter like the respiratory quotient (RQ). Sea level (SL) volunteers (7 women and 7 men, 21.0 ± 2.04 y) were examined for daily changes in salivary melatonin concentration (SMC). Sampling was successively done at SL (Antofagasta, Chile) and, on acute HA exposure, at nearby Caspana (3,270 m asl). Saliva was collected in special vials (Salimetrics Oral Swab, United Kingdom) at sunny noon (SMC_D) and in the absence of blue light at midnight (SMC_N). The samples were obtained after rinsing the mouth with tap water and were analyzed for SMC by immunoassay (ELISA kit; IBL International, Germany). RQ measurements (n = 12) were realized with a portable breath to breath metabolic system (Oxicon^TM Mobile, Germany), between 8:00 PM and 10:00 PM, once at either location. At SL, SMC_D, and SMC_N values (mean ± SD) were, respectively, 2.14 ± 1.30 and 11.6 ± 13.9 pg/ml (p < 0.05). Corresponding values at HA were 8.83 ± 12.6 and 13.7 ± 16.7 pg/ml (n.s.). RQ was 0.78 ± 0.07 and 0.89 ± 0.08, respectively, at SL and HA (p < 0.05). Differences between SMC_N and SMC_D (SMC_N–SMC_D) strongly correlate with the corresponding RQ values at SL (r = -0.74) and less tight at HA (r = -0.37). Similarly, mean daily SMC values (SMC) tightly correlate with RQ at SL (r = -0.79) and weaker at HA (r = -0.31). SMC_N–SMC_D, as well as, SMC values at SL, on the other hand, respectively, correlate with the corresponding values at HA (r = 0.71 and r = 0.85). Acute exposure to HA appears to loosen relations of SMC with RQ. A personal profile in daily SMC variation, on the other hand, tends to be conserved at HA.

Previous results evidenced acute exposure to high altitude (HA) weakening the relation between daily melatonin cycle and the respiratory quotient. This review deals with the threat extreme environments pose on body time order, particularly concerning energy metabolism. Working at HA, at poles, or in space challenge our ancestral inborn body timing system. This conflict may also mark many aspects of our current lifestyle, involving shift work, rapid time zone crossing, and even prolonged office work in closed buildings. Misalignments between external and internal rhythms, in the short term, traduce into risk of mental and physical performance shortfalls, mood changes, quarrels, drug and alcohol abuse, failure to accomplish with the mission and, finally, high rates of fatal accidents. Relations of melatonin with energy metabolism being altered under a condition of hypoxia focused our attention on interactions of the indoleamine with redox state, as well as, with autonomic regulations. Individual tolerance/susceptibility to such interactions may hint at adequately dealing with body timing disorders under extreme conditions.

Background: Testicular aches have been reported to occur on exposure to high altitude (HA). As a painful expression of venous congestion at the pampiniform plexus, varicocele (VC) might be a consequence of cardiovascular adjustments at HA. Chile’s National Social Security Regulatory Body (SUSESO) asked to evaluate this condition in the running follow-up study “Health effects of exposure to chronic intermittent hypoxia in Chilean mining workers.” Objectives: To investigate the prevalence of VC in a population usually shifting between sea level and HA, thereby intermittently being exposed to hypobaric hypoxia. Methodology: Miners (n=492) agreed to be examined at their working place by a physician, in the context of a general health survey, for the presence of palpable VC, either visible or not. Among them was a group exposed to low altitude (LA) 3,900 m, n=165. The Chi2 test and Kruskal-Wallis test were used in the descriptive analysis, and logistic regression was applied to evaluate the association of VC with exposure to HA. The Ethics Committee for Research in Human Beings, Faculty of Medicine, University of Chile, approved this project. Results: VC prevalence (grades 2 and 3) was found to be 10% at LA, 4.1% at MHA and 16.7% at VHA (p≤0.05). Hemoglobin oxygen saturation (SaO2) was lower, and hemoglobin concentrations were higher in workers with high grade VC at VHA compared with LA and MHA (Wilcoxon tests, p<0.001). Odds ratios (OR) for association of VC with HA were 3.7 (95%CI: 1.26 to 12.3) and 4.06 (95%CI: 1.73 to 11.2) for MHA and VHA, respectively Conclusions: Association of VC with HA, a clinically relevant finding for its own sake, may be related to blood volume centralization as mediated by hypobaric hypoxia.