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

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.