Sex difference in irritable bowel syndrome: do gonadal hormones play a role?

Sex and gender effects in irritable bowel syndrome (IBS) have been reported in epidemiological, physiological, and clinical treatment studies. The potential role of gonadal hormones is discussed based on the female predominance in IBS and the correlation between IBS symptoms and hormonal status. Several different models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function, including changes in GI symptoms during the menstrual cycle and differences in symptom expression in pre- and post-menopausal women as well as changes during pregnancy, hormonal treatment, or after ovariectomy. Gonadal hormones, in particular estrogens, can significantly modulate various clinical manifestations of IBS, including alterations in GI motility and visceral hypersensitivity. Additionally, sex differences in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system are considered to be contributing factors in the pathogenesis of functional bowel disorders. The modulatory effects of estrogens on visceral pain may result from interactions with numerous neurotransmitters at different levels of the brain-gut axis, with a pivotal role of estrogens' interactions with the serotonin and corticotropin-releasing factor (CRF) signaling systems. Estrogens can also modulate neuroimmune interactions triggered by stress via the brain-gut axis. Sex differences in the biological actions, pharmacokinetics, and treatment efficacy of serotonergic medications clearly suggest sex differences in pain pathways that have to be taken into consideration in therapeutic interventions.