Impact of the menstrual cycle on oxidative stress, inflammation and iron status at high altitude

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Abstract

High altitude may alter redox balance and promote inflammation. It remains unclear if ovarian hormone fluctuations influence redox status. We sought to investigate the impact of menstrual cycle (MC) phases on oxidative stress, nitric oxide metabolism, inflammation, iron biomarkers and acute mountain sickness (AMS) during high-altitude sojourns in eumenorrheic women. Venous blood samples were collected at low altitude (1224 m) and after one night at 3375 m (Rifugio Torino, inspired O2 pressure: 96 ± 1 mmHg) during both the early follicular (EF) and mid-luteal (ML) phases. At high altitude, xanthine oxidase (XO: 0.140 ± 0.077 vs. 0.165 ± 0.084 μmol L-1 min -1; p = 1.00), total nitrites and nitrates (NOx: 38.9 ± 10.8 vs. 32.8 ± 6.1 μmol L-1; p = 1.00), interleukin-6 (IL-6: 17.3 ± 13.6 vs. 14.5 ± 13.2 ng mL-1; p = 1.00) and serum iron concentration (19.7 ± 6.8 vs. 22.1 ± 4.6 μmol L-1; p = 1.00) were not significantly different between EF and ML. However, total protein concentrations were significantly lower in EF compared to ML (75.5 ± 2.0 vs. 80.0 ± 5.1 g L-1; p = 0.010). No significant differences were observed in Lake Louise scores (AMS) between EF and ML (2.17 ± 1.64 vs. 1.50 ± 1.83; p = 0.180). High-altitude exposure increased XO, IL-6 and erythropoietin levels and decreased NOx, when compared to low altitude. These findings suggest that redox balance, nitric oxide bioavailability, inflammation and iron homeostasis are not influenced by the MC at high altitude. Overall, susceptibility to AMS was similar across MC phases.

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Tagliapietra, G., Citherlet, T., Raberin, A., Narang, B. J., Manferdelli, G., Giardini, G., … Millet, G. P. (2026). Impact of the menstrual cycle on oxidative stress, inflammation and iron status at high altitude. Nitric Oxide : Biology and Chemistry, 160, 56–62. https://doi.org/10.1016/j.niox.2025.12.001

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