Biological, Metabolic, Lifestyle, and Clinical Factors Leading to a Faster Increase of Gallstone Disease Prevalence in Men

Abstract

Gallstone disease remains one of the most prevalent disorders of the hepatobiliary system and a major driver of healthcare utilization worldwide. Although gallstones have historically been more frequent in women, multiple populations now report a relative rise in incident gallstone disease among men, coinciding with shifts in cardiometabolic risk profiles, aging demographics, and medication exposures. This review synthesizes contemporary evidence on factors that increase gallstone incidence in men, integrating epidemiologic trends with mechanistic pathways in cholesterol supersaturation, gallbladder dysmotility, inflammation, and metabolic dysregulation. Particular emphasis is placed on male-relevant determinants: central obesity and insulin resistance, type 2 diabetes, hypertension and vascular disease, smoking, dietary quality, physical inactivity, and endocrine contexts such as androgen deprivation therapy. Interactions between nonalcoholic fatty liver disease and gallstone disease are examined as convergent outcomes of metabolic dysfunction. Evidence from large prospective cohorts, systematic reviews, and population-based studies is discussed to highlight modifiable risk factors, identify high-risk male subgroups, and inform prevention and early detection strategies. The most actionable prevention strategy in men is comprehensive cardiometabolic risk reduction: maintaining healthy body weight and waist circumference, improving diet quality, increasing physical activity, and eliminating tobacco use. Viewing gallstones in men as a potential marker of metabolic dysfunction and broader chronic disease risk can strengthen preventive care and may reduce both biliary complications and downstream cardiometabolic burden.