{
  "abstract": "ImportanceAcute mountain sickness (AMS) is a common high-altitude illness partly preventable by acetazolamide, but sex-specific efficacy and tolerability have not been prospectively evaluated.\n\nObjectiveTo test the a priori hypothesis that preventive acetazolamide achieves a 20% greater relative risk reduction (RRR) of AMS in female vs male lowlanders ascending to 3600 m.\n\nDesignRandomized, double-blind, placebo-controlled, parallel-group trial conducted from March 2024 to August 2025; participants, outcome assessors, and statistician were blinded until analysis was complete.\n\nSettingBaseline at 760 m in Bishkek and altitude exposure at the Kumtor High Altitude Facility (3600 m), Kyrgyz Republic.\n\nParticipantsHealthy female and male low-altitude residents (age 18-44 years, BMI 18-30 kg/m2, residence <1000 m); females were premenopausal, eumenorrheic, and not using hormonal contraception. Exclusion criteria included pre-existing disease, regular medication, pregnancy, anaemia, and altitude sojourn >2500 m within 4 weeks.\n\nInterventionAcetazolamide 125 mg or matching placebo twice daily, from 24 hours before ascent and throughout the 2-day, 2-night stay at 3600 m.\n\nMain Outcomes and MeasuresPrimary outcome was the between-sex difference in RRR of AMS, defined as a 2018 revised Lake Louise Score of 3 or higher including headache. Secondary outcomes included absolute risk reduction (ARR) and drug tolerability.\n\nResultsOf 303 randomized participants (180 females, 123 males; mean [SD] age, 23 [4] years), AMS incidence under placebo (n=155) was 34% (females 42% vs males 23%; P=.02) and under acetazolamide (n=148) was 24% (females 30% vs males 14%; P=.02). Overall RRR was 31% (95% CI, 0% to 52%) and ARR was 10% (95% CI, 0% to 22%). Sex-stratified RRR was 27% (95% CI, -9% to 52%) in females and 42% (95% CI, -28% to 74%) in males; between-sex RRR difference, -15% (95% CI, -65% to 57%). Females had a 4.8-fold higher risk of moderate-to-severe drug-related side effects than males.\n\nConclusions and RelevancePreventive acetazolamide reduced overall AMS incidence at 3600 m, but the pre-specified 20% greater RRR in females (trial powered at 90%) was not observed. The nearly 5-fold higher risk of moderate-to-severe side effects in females warrants further investigation of sex-specific dosing.\n\nTrial RegistrationClinicalTrials.gov Identifier: NCT06499727\n\nKey PointsO_ST_ABSQuestionC_ST_ABSDoes preventive acetazolamide reduce acute mountain sickness (AMS) more effectively in female than in male lowlanders ascending to 3600m?\n\nFindingsIn this randomized, double-blind, placebo-controlled trial of 303 healthy lowlanders, preventive acetazolamide did not achieve a greater relative risk reduction of AMS in females than in males; the pre-specified 20% between-sex difference, for which the trial was 90% powered, was not observed. However, females experienced a 5-fold higher risk of moderate-to- severe drug-related side effects than males.\n\nMeaningPreventive acetazolamide reduces AMS in healthy lowlanders without demonstrating sex-specific efficacy, but its worse tolerability in females warrants investigation of sex-specific dosing.",
  "abstract_shown": true,
  "affiliations": [
    "University Hospital Zurich, Pulmonology Department, Zurich, Switzerland"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "A. Taalaibekova"
    },
    {
      "name": "J. Roche"
    },
    {
      "name": "A. Haefliger"
    },
    {
      "name": "D. Hertig"
    },
    {
      "name": "M. Mademilov"
    },
    {
      "name": "K. Magdieva"
    },
    {
      "name": "A. Bolotbek"
    },
    {
      "name": "G. Mirzalieva"
    },
    {
      "name": "T. Li"
    },
    {
      "name": "K. von Gruenigen"
    },
    {
      "name": "A. Vella"
    },
    {
      "name": "S. Zahner-Ulrich"
    },
    {
      "name": "B. Champigneulle"
    },
    {
      "name": "J. Mueller"
    },
    {
      "name": "M. Lichtblau"
    },
    {
      "name": "S. Verges"
    },
    {
      "name": "K. E. Bloch"
    },
    {
      "name": "S. Ulrich"
    },
    {
      "name": "T. M. Sooronbaev"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Furian"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9zydn3y79ppyp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.09.26362614",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.09.26362614v1.full",
  "id": "9zydn3y79ppyp",
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  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.09.26362614v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "respiratory medicine"
    ],
    [
      "openalex",
      "1311|High Altitude and Hypoxia"
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  "openalex": "W7212354925",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.09.26362614v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9zydn3y79ppyp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:23Z",
      "native_id": "10.64898/2026.09.09.26362614",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.09.26362614v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|High Altitude and Hypoxia",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Sex-specific efficacy of acetazolamide for acute mountain sickness. A randomised clinical trial.",
  "title_text": "Sex-specific efficacy of acetazolamide for acute mountain sickness. A randomised clinical trial.",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:23Z",
  "url": "https://research.draconitic.com/paper/9zydn3y79ppyp",
  "venue": "medRxiv",
  "versions": []
}