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