Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

Abstract

According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical to decipher how stress, ovarian hormones, and female brain processing of pain can translate into gut dysfunctions.

Keywords: Irritable bowel syndrome; Pathophysiology; Gender; Sex hormones; Gut; Sensori-motricity; Neurosensitization; Stress; Immune activation; Permeabilization

Core tip: This review summarizes the current knowledge on the role of ovarian hormones in the pathophysiology of irritable bowel syndrome (IBS). A better understanding of gender differences in IBS may help unveil some key mechanisms contributing to IBS development. We present data on: (1) the modulatory role of ovarian hormones on IBS symptoms; (2) influence of ovarian hormones on risk factors associated with IBS; and (3) potential mechanisms of action, by which ovarian hormones can modulate and/or induce IBS symptoms.