Sex-Specific Difference in Health-Related Altitude-Effects and Their Prevention by Acetazolamide. Data from a Randomized Controlled Trial.

Häfliger, Alina, Aline Buergin, Laura C. Mayer, Maamed Mademilov, Mona Lichtblau, Talantbek Sooronbaev, Silvia Ulrich, Konrad E. Bloch, and Michael Furian. Sex-specific difference in health-related altitude-effects and their prevention by acetazolamide. Data from a randomized controlled trial. High Alt Med Biol. 26:195-203, 2025. Background: Women are underrepresented in studies on acute mountain sickness (AMS), altitude-induced sleep-disordered breathing and preventive acetazolamide use. Methods: We analyzed sex-specific altitude-effects in participants of a randomized, placebo-controlled, double-blind trial in healthy lowlanders >40 years. Participants took 375 mg/day acetazolamide or placebo starting 24 hours before ascent to and while staying 2 days at 3,100 m. Main outcomes of this analysis were sex-specific incidence of AMS (Lake Louise score ≥3), nocturnal pulse oximetry (SpO2) and apnea-hypopnea index (AHI) at 3,100 m. Results: With placebo, 30 of 119 (25%) women and 4 of 51 (8%) men developed AMS (p = 0.009 between sexes) at 3,100 m. Among women assigned to placebo, SpO2 (mean ± SE 84 ± 0%) and AHI (16.9 ± 1.3/h) in night 1 at 3,100 m were lower compared to men (SpO2 86 ± 0%; AHI 28.3 ± 1.9/h), despite similar baseline values at 760 m. Mean between-sex difference in altitude-effects (women-men) in SpO2 was -1.4% (95% CI, -2.4 to -0.3%); AHI -10.7/h (95% CI, -15.7 to -5.7/h). The impact of acetazolamide on AMS was not significant for either sex but acetazolamide improved AHI in men (difference men-women, -9.8/h [95% CI, -16.8 to -2.7/h]). Conclusion: This study suggests sex-specific differences in altitude-induced hypoxemia, periodic breathing, AMS incidence, and in the response to preventive acetazolamide treatment.