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

Functional gastrointestinal (GI) disorders (FGIDs) are a result of central and peripheral mechanisms.

It is suggested that biological disturbances, such as persistent mucosal inflammation after acute gastroenteritis that interacts with other environmental factors and psychological stressors, which influence the brain and gut to alter GI tract motility or sensation, thereby causing symptoms. 

FGIDs cause chronic remitting-relapsing symptoms, and are associated with comorbid conditions and impaired quality of life. 

Functional dyspepsia (FD) and irritable bowel syndrome (IBS) together affect approximately 1 in 4 people in the United States. 

Functional GI diseases 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 are more common in women.

Diarrhea is more common in men.

Slow gastric emptying and colon transit are more common in healthy women than in men.

Approximately one third of the adult population has 1 or more gastrointestinal symptoms: dyspepsia, constipation, diarrhea, chronic abdominal pain, or fecal incontinence.

FGID account  for a majority of gastroenterology consultations.

FGID patients often have chronic remitting-relapsing symptoms, comorbid conditions, such as, fibromyalgia, anxiety, depression, and impaired quality of life (QOL).

Functional gastrointestinal disorders

are disorders of gut functions, especially gastrointestinal (GI) tract motility and sensation. 

There may be subtle 

abnormalities of microscopic inflammation, or altered gut microbiota in some patients. 

Psychosocial conditions and stressors contribute to the development, perception, and management of FGIDs.

The 2 most common FGIDs: functional dyspepsia (FD) and irritable bowel syndrome (IBS).

Similar to other disorders accompanied by chronic pain, such as fibromyalgia, migraine, and rheumatoid arthritis, functional dyspepsia and IBS are more common in women than in men. 

Chronic constipation estimate is prevalence of 16%, and the female:male ratio (1.5:1).

Among patients with IBS, constipation 

Is more common in women. 

Among patients with IBS, diarrhea is more common in men.

Bloating in IBSb is more common in women.

Women with IBS have more severe symptoms during menses.

Anxiety and depression are more common in female than male patients with IBS. 

The level of anxiety correlates with some IBS symptoms in women, but not men.

Women are at increased risk for postinfectious IBS after acute gastroenteritis illness.

Gastric emptying and colon transit are slower in healthy women than men.

Studies  find that during rectal distension there is greater activation of affective and autonomic regions in women, while in men there is activation of regions belonging to a corticolimbic pain inhibition system.

In a pharmacologic model using intravenous hydrocortisone, the 

acute stress of intravenous hydrocortisone increases  rectal sensation of distention in women but not men.

In IBS, colonic mucosal biopsies have more mast cells but fewer CD3+ and CD8+ T cells for women than men.

Men have greater hypothalamus-pituitary-adrenal axis and sympathetic responses to stress than women.

There is slower gastric emptying and colon transit in healthy women than in men.

Progesterone accelerates colonic transit in postmenopausal healthy women.

There is no evidence of sex-related differences for fecal or colonic mucosal microbiome in IBS.

The  overall questionnaire-based prevalence of dyspepsia has a female:male ratio of 11:7.

For adults older than 65 years, the prevalence of dyspepsia is similar in men and women. 

There may be gender-based differences in communicating bodily discomfort, with women choosing more diverse, detailed, and emotional terms and a broader spectrum of presenting symptoms compared with men when expressing discomfort.

IBS disease is more common in women (14%) than in men (9%).

In tertiary centers, the female:male ratio is generally higher, at 3:1.

A meta-analysis of clinic-based studies of IBS:  

constipation predominant women, 40%; men, 21%.

diarrhea predominant women, 31%; men, 50%.

Mixed IBS, constipation and diarrhea, did not show a statistically significant difference between men and women. 

Gastrointestinal symptoms of bloating and abdominal distention are more common and severe for women than men with IBS.

Women with IBS report harder stools, more somatic symptoms, less sense of coping, general anxiety and GI tract–specific anxiety, and impaired quality of life.

Approximately 6.6% of the US population had chronic diarrhea.

The prevalence of chronic diarrhea is greater in women than in men.

Microscopic colitis causes diarrhea, and it is more common in women than in men.

There is a greater prevalence of IBS–constipation type (IBS-C) in women than in men. 

Bloating is more commonly a source of physical discomfort and psychological distress for women.

Sex-related differences in the prevalence of upper gastrointestinal symptoms seem smaller than corresponding differences in lower gastrointestinal symptoms. 

Patients with IBS were approximately 3-fold more likely to have anxiety, which was more common in women than in men.

Depressive symptoms also were more common in women than in men.

It is suggested greater anxiety and depression in women alter central pain processing and predispose to more severe GI tract symptoms in women. 

Anxiety and depression in women are associated with more severe GI and non-GI somatic symptoms and a lower quality of life.

Among patients with acute gastroenteritis, self-reported anxiety and depression were each associated with a 2-fold increased risk of IBS

Among community residents, persons with anxiety or depression, or both, are at increased risk for incident functional disease, functional GI disease or IBS.

Conversely, persons with FGID at baseline were at increased risk for anxiety or depression several years later.

These outcomes are not different in men compared with women. 

There is a bidirectional relationship between anxiety, depression and the FGIDs. 

For women with IBS-C, the severity of anxiety was associated with abdominal discomfort and abdominal pain, but not with abdominal bloating. 

For men with IBS-C, the severity of anxiety did not show a statistically significant association with abdominal bloating, discomfort, or pain.


Fibromyalgia is more prevalent in women than men.

Fibromyalgia affects 26% to 65% of patients with IBS.

32% to 70% of fibromyalgia patients have IBS.

Among patients with fibromyalgia, IBS was less prevalent in men than in women.

Compared with men with IBS menstruating and postmenopausal women have significantly higher symptom scores of backache, headache, joint pain, and muscle pain.

The prevalence of sexual dysfunction (43%) is similar for men and women with functional gastrointestinal diseases.

A higher proportion of women (35%) than men (32%) with overactive bladder have concurrent IBS.

A small proportion of patients with , and more often women than men, have a history of  or an ongoing eating disorder. 

With functional dyspepsia or IBS physical and mental QOL is poorer for women than men.

Gastric emptying and colonic transit are slower, and the variation of colonic transit is greater for healthy women than for men.

Female sex is an independent risk factor for delayed gastric emptying for patients with functional disease, implicating a loss of colonic nerves and interstitial cells of Cajal.

Studies have shown that sex hormones affect pain processing in humans.

Visceral pain is often regarded as more unpleasant, and it is more difficult to localize than somatic pain.

Visceral hypersensitivity consists of 2 components: allodynia, in which an innocuous stimulus is perceived as painful, and hyperalgesia, defined as a more intense perception of a painful stimulus.

Patients with visceral hypersensitivity have more severe IBS symptoms.

A majority of patients in these studies are women.

Among patients with IBS, bowel symptoms and rectal sensation are more intense during menses than during the follicular, luteal, or premenstrual phases.

Studies suggest that bowel symptoms are worse during menses than other phases of the menstrual cycle for women with IBS.

Postmenopausal women who are being or had been treated with hormone replacement had increased risk of IBS compared with nonusers.

Assessments of somatic sensation (ie, pinprick pain sensitivity, incision-induced pain, and pinprick hyperalgesia) were significantly correlated with plasma P4 and follicle-stimulating hormone and negatively correlated with testosterone in humans. 

Among patients with IBS, rectal sensory thresholds inversely correlated with serum testosterone levels.

The spinal and vagal afferents from the GI tract indirectly project to the thalamus, insula, amygdala, prefrontal cortex, primary somatosensory cortex, secondary somatosensory cortex, and cingulate cortices, including the anterior cingulate cortex.

The intensity and location of visceral pain is reflected by the somatosensory cortices of the lateral pain system.

The cingulate cortex is the the medial pain system, and it is implicated in the emotional interpretation of the stimulus.

The insula serves to process of the affective dimension of pain, integrate it with emotional information, and inform the amygdala, hypothalamus, and periaqueductal gray. 

The amygdala is critical to affective fear, and painful sensation.

The amygdala has a key role in the descending modulation of pain.

At rest, the female brain allocates greater resources to interoceptive awareness of stimuli originating in the body, whereas the male brain relies more on cognitive function.

Differences in the effective connectivity of emotional arousal circuitry, rather than visceral afferent processing circuitry, that explain the differences between men and women in relation to GI functional disease.

Observations suggest that sex steroids do not contribute substantially to visceral hypersensitivity in patients with IBS.

Acute gastroenteritis is the most important risk factor for IBS and, to a lesser extent, functional disease in children83 and adults.

After infectious enteritis, IBS symptoms occur in 10.1% at 12 months and 14.5% at more than 12 months.

One in 6 persons in the United States has acute infectious gastroenteritis every year.

Postinfectious IBS probably accounts for a substantial proportion of new cases of IBS.

Female sex, younger age, psychological distress during or before acute gastroenteritis, and more severe acute enteritis are risk factors for postinfectious IBS.

Compared with male patients, female patients with IBS had more gastrointestinal mucosal mast cells, which were correlated with the severity of GI tract symptoms, but fewer CD3+ and CD8+ T cells.

Women have a greater prevalence of various autoimmune diseases, including Sjögren syndrome, scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.

Acute diarrhea is more likely to increase rectal sensitivity, which is a feature of IBS, in women than men.

The sex distribution of patients with postinfectious and unspecified-onset FD is comparable or different.

Psychosocial stressors include environmental factors and psychological distress (ie, mood disorders, anxiety, somatization, and cognitive-affective processes) that influence the brain and the gut and are associated with FGIDs. 

Environmental factors include social constructs and behavior, parenteral anxiety, depression, somatization, and adverse early life experiences including physical, sexual, and emotional abuse, are all strongly associated with abdominal symptoms.

Gender-related social or societal expectations, such as standards for attractiveness, norms for women’s caretaking role in relationships, and sanctions against anger expression by women, can impair health and well-being.

Among patients with IBS, women described shame because they were not living up to gender norm expectations for women in the domains of relationships: taking care of others at the expense of their own needs, attractiveness, and lack of desire to engage in sex.

Men were more concerned about the effect of IBS symptoms on paid employment and sense of control. 

Men are  also were embarrassed by IBS symptoms, but have more relaxed attitude to feces and passing wind than women.

During health care visits, women risked being trivialized, and men risked being overlooked because IBS might be regarded as a health concern for women only.

Children whose mothers reinforce illness behavior have more severe stomach aches and more school absences than other children.

More common in persons with IBS than healthy control persons are physical punishment, emotional abuse, and sexual abuse, which often coexist, are related to the severity and clinical outcomes of FGIDs. 

The prevalence of childhood and adulthood abuse is more common in women who had FGID (45%) than in women in the control group without GI tract symptoms (16%).

The corresponding prevalence was not different in men with FGID (29%) versus without it (24%). 

A history of sexual abuse has been associated with FGIDs, nonspecific chronic pain, chronic pelvic pain, and psychogenic seizures, but not with fibromyalgia or headache.

The extent to which gender affects the relationship between stressful events, abuse, and IBS is unknown.

Stress activates the hypothalamic-pituitary-adrenal axis, and the cortisol response to mental stressors is greater in healthy men than in healthy women.

Mediators of stress participate in the pathophysiologic characteristics and persistence of chronic pain. 

Hydrocortisone increases the sensitivity for visceral but not somatic pain in women versus men.

It is suggested that cortisol primarily affects visceral sensory-discriminatory aspects, or pain sensitivity, rather than cognitive-evaluative or affective pain components for healthy persons.

Among patients with IBS, the autonomic response of increased sympathetic and decreased parasympathetic activity to rectosigmoid distension is  more pronounced in men than women, but 

unclear whether the exaggerated autonomic response in men is correlated with the severity of daily symptoms or rectal sensory thresholds.

Compared with sex-matched healthy controls, the cortisol release factor-induced ACTH release and the ACTH-evoked cortisol response was increased in men and decreased in women with IBS.

Intravenous hydrocortisone increased rectal sensitivity in healthy women. 

The CRF-induced ACTH release and the ACTH-evoked cortisol response were increased for male IBS patients and decreased for women with IBS. 

Mechanical and chemical stimuli release serotonin from enteric neurons and mucosal enterochromaffin cells. 

Serotonin initiates motor reflexes and visceral sensation. 

Sex-related differences in GI tract serotoninergic pathways and the brain-gut axis might contribute to differences among the sexes in IBS. 

Postprandial plasma serotonin levels are higher in female patients with IBS and elevated progesterone and estrogen levels compared with patients with low hormone levels.

Serotonin turnover is reduced in female patients with IBS, and elevated serotonin levels could be due to defects in uptake or metabolism.

IBS is associated with serotoninergic disturbances, the functional importance of which is unclear.

Acute psychological stress increases intestinal permeability through corticotropin-releasing hormone and mast cell–dependent mechanisms.

Certain foods cause GI tract symptoms either directly or after microbiome-induced fermentation of carbohydrates to short-chain fatty acids or metabolism with bile acids.

The diet can modify the gut microbiome. 

While the  gut microbiome differs between patients with IBS and control patients, no specific microbial signature is associated with IBS.

Studies suggest that there is a heritable component to IBS, but in a sample of 45,750 Swedish twins, investigators saw no evidence of sex differences in heritability of IBS.

There is a significant association between chromosome 9q31.2 (single-nucleotide polymorphiand women with IBS-C in some countries.

Men manage their pain through self-distraction and problem-focused challenges, whereas women resort to emotion-focused tactics, catastrophizing, positive self-statements, and social support.

Expression of pain is socially more acceptable among women, whereas men show increased pain tolerance and greater resistance in reporting pain.

Women with IBS are more likely than men to seek health care.

Most patients enrolled in the pharmacologic and behavioral trials of FD and IBS are women.

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