Sex- and Gender-Related Differences in Common Functional Gastroenterologic Disorders

Abstract

Functional gastrointestinal (GI) disorders (FGIDs) result from central and peripheral mechanisms, cause chronic remitting-relapsing symptoms, and are associated with comorbid conditions and impaired quality of life. This article reviews sex- and gender-based differences in the prevalence, pathophysiologic factors, clinical characteristics, and management of functional dyspepsia (FD) and irritable bowel syndrome (IBS) that together affect approximately 1 in 4 people in the United States. These conditions are more common in women. Among patients with IBS, women are more likely to have severe symptoms and coexistent anxiety or depression; constipation or bloating and diarrhea are more common in women and men, respectively, perhaps partly because defecatory disorders, which cause constipation, are more common in women. Current concepts suggest that biological disturbances (eg, persistent mucosal inflammation after acute gastroenteritis) interact with other environmental factors (eg, abuse) and psychological stressors, which influence the brain and gut to alter GI tract motility or sensation, thereby causing symptoms. By comparison to a considerable understanding of sex-based differences in the pathogenesis of visceral hypersensitivity in animal models, we know less about the contribution of these differences to FGID in humans. Slow gastric emptying and colon transit are more common in healthy women than in men, but effects of gonadal hormones on colon transit are less important than in rodents. Although increased visceral sensation partly explains symptoms, the effects of sex on visceral sensation, colonic permeability, and the gut microbiome are less prominent in humans than rodents. Whether sex or gender affects response to medications or behavioral therapy in FD or IBS is unclear because most patients in these studies are women.

Figure 1.

Prevalence of Common Functional Gastrointestinal Tract and Somatic Disorders of Men and Women. Values are approximate and are derived from individual population-based studies or systematic reviews. For chronic constipation, the estimate is derived from the average prevalence (16%) and the female to male ratio (1.5:1) in systematic reviews and with the assumption that the female to male ratio is 1:1 in the general population.

Figure 2.

Sex- and Gender-Based Differences in the Pathogenesis of Common Functional GI Tract Disorders. Peripheral disturbances (ie, postinfectious irritable bowel syndrome) and central factors (eg, psychological stressors) cause GI tract sensory and motor dysfunctions that contribute to symptoms. The peripheral mechanisms include triggers (eg, postinfectious inflammation, bile acids) that stimulate enterochromaffin cells, may change mucosal permeability, and activate immune mechanisms to stimulate afferent nerves. Central sensitization may result from this peripheral sensitization and/or reduced descending inhibition, which normally gates visceral sensation in the spinal cord. Sex-related differences in activation of brain centers and mechanisms are shown in colors. Difference between male and female sexes in humans are shown in blue and dark pink; corresponding differences only observed in animal models are shown in olive. ACC indicates anterior cingulate cortex; CGRP = calcitonin gene-related peptide; CRF = corticotropin-releasing factor; 5-HT = serotonin; GDNF = glial cell line–derived neurotrophic factor; GI = gastrointestinal; HPA = hypothalamic-pituitary-adrenal; IFNγ = interferon gamma; L = left; PAG = periaqueductal gray; PAR2 = proteinase-activated receptor 2; PFC = prefrontal cortex; R = right; TNF, tumor necrosis factor.