Sex-sensitive and insensitive endocrine responses and infradian changes while trekking in the Himalayas

Various studies have explored the effects of altitude hypoxia on hormonal changes. However, most research has been conducted on small samples and focused solely on male subjects. This project aimed to examine the effects of high-altitude trekking on the hypothalamic-pituitary-gonadal axis and the hormonal stress response, with particular attention to potential gender differences in hormonal fluctuations. A Himalayan expedition was conducted with 21 volunteers (12 men, 9 women), aged 43 ± 15 years, with a BMI of 24.2 ± 3.70 kg/m². Participants took a 250 mg pill of acetazolamide once daily. Blood samples were collected before, during, and after the ascent to a Pyramid Laboratory - Observatory (altitude approximately 5,000 m above sea level). Five females were premenopausal, all in the follicular phase of their menstrual cycle. A longer cycle duration was observed in all of them in response to the high-altitude expedition. Gonadotropin levels remained unchanged in both sexes. Differential trends according to sex emerged for: 17β-estradiol, as females showed a decrease from low to high altitude, while males’ reductions were delayed; prolactin, whose decline at high altitude was more pronounced in females; progesterone, as males exhibited higher values at high altitude than at low altitude, whereas the overall trend was flat in females. The dysregulation of the endocrine system at high altitude is subclinical and reversible in both sexes, at least up to 5,000 m a.s.l. The significant prolongation of the menstrual cycle in response to hypoxia warrants further detailed analyses. • altitude hypoxia leads to longer menstrual cycles in humans. • rather than cortisol, prolactin is a highly responsive hormone in both sexes to the combined stressors of trekking and altitude hypoxia. • prolactin, progesterone ed estradiol exhibited a sex-sensitive response.