Sex and Gender Differences in Peptic Ulcer Disease: A Scoping Review with Exploratory Quantitative Synthesis for Clinical Guideline Development

Background/Aims: Peptic ulcer disease (PUD) exhibits sex-based differences in epidemiology and treatment that shift across the lifespan; however, there are no sex-specific recommendations in the current guidelines.For this scoping review, sex and gender differences in PUD were mapped to inform guideline development.Methods: Following the PRISMA-ScR guidelines, we searched PubMed, Embase, the Cochrane Library, and KoreaMed through October 2025.Two reviewers independently screened articles and extracted data on epidemiology, hormonal factors, treatment responses, and outcomes. Results:Of the 940 identified records (895 from databases and 45 from manual searching), 68 studies met the inclusion criteria.Key findings were organized into three thematic domains-Epidemiology: the male-to-female PUD ratio has narrowed from 2:1 to near parity, with elderly females (≥70 years) demonstrating elevated bleeding and mortality risk, particularly with concurrent nonsteroidal anti-inflammatory drug or aspirin use; Hormonal factors: both natural and surgical menopause were consistently associated with increased PUD risk, with a stronger association for surgical menopause.Postmenopausal females had higher perforation and mortality rates; and Treatment response and pharmacology: females experienced twice as many adverse events during Helicobacter pylori therapy despite similar eradication rates and had higher H. pylori recurrence rates.Females showed approximately 30% higher plasma proton pump in- hibitor (PPI) concentrations, suggesting pharmacokinetic differences.An exploratory quantitative synthesis suggested a sex-specific benefit of PPI gastroprotection in anticoagulated females, requiring confirmation.Conclusions: Substantial sex-based differences in PUD epidemiology, hormonal factors, and treatment response remain unaddressed in current guidelines.In the future, those developing guidelines should consider incorporating postmenopausal status into risk stratification, gastroprotection measures for elderly females on antithrombotic therapy, and sex-specific pharmacokinetic differences in PPI dosing.(Gut Liver, Published online June 30,