Irritable bowel syndrome (IBS) is a disorder characterized by chronic abdominal pain or discomfort and altered bowel habits. IBS is the most frequently diagnosed gastrointestinal (GI) condition, with an estimated US prevalence of 5%–25%. The diagnosis of IBS is established by fulfilling the symptom-based Rome III criteria. IBS accounts for 36%–50% of all referrals to gastroenterologists but is often seen in primary care settings as well. In a study to assess the economic burden and health care usage of various GI disorders, IBS accounted for 3.7 million annual office visits, being second only to the number of visits for gastroesophageal reflux. IBS and disorders with which it is related has been associated with a significant decrease in quality of life. Functional GI disorders that include IBS have been shown to negatively impact quality of life more so than ‘‘organic’’ GI disorders, such as inflammatory bowel disease. Along these lines, IBS is the second leading cause of work absenteeism. IBS appears to have a female predominance, with two-thirds of patients being women. While the greater prevalence among women is well established, the reasons for this sex difference remain elusive. IBS in women appears to be linked to other chronic functional pain disorders that are sex-based, such as fibromyalgia, chronic fatigue syndrome, chronic constipation, interstitial cystitis, and migraine headaches with aura and temporomandibular joint disorder.
Historically, IBS research has not focused on sex comparisons despite that the overwhelming majority of study subjects have been female. In addition, women in past studies were often treated as a homogenous group, with little attention paid to menopausal status, menstrual cycle, use of hormones (i.e., oral contraceptives, hormone replacement therapy), or other sex-related factors . Recent interest in sex differences in IBS has been fuelled in part by studies suggesting that new pharmacological therapies for this syndrome are more effective in female than in male IBS patients. There is growing evidence that clinical symptoms differ between male and female IBS patients and are also affected by the menstrual cycle. This review will focus on sex differences in IBS, including epidemiology, clinical presentation, pathophysiology, treatment response, and dietary management.
ETIOLOGY AND SEX DIFFERENCES
PREVALENCE OF IBS
In the general population, the female-to-male prevalence ratio for IBS varies between 1:1 and 2:1 across a variety of studies. Women are more likely to seek medical care for this condition, as reflected by the even greater female predominance seen in medical clinic populations, as high as 4:1 in one survey. Some of this variability can likely be accounted for by cultural factors and sex differences in rates of health care utilization, given that several studies conducted in India and Sri Lanka actually report a male predominance among IBS clinic patients.
There have been several studies comparing symptoms between men and women with IBS. Findings have been variable and inconsistent, likely because of differences in sample recruitment sites (community vs. tertiary care clinic) and data collection methodology (daily diary, interview, chart review, questionnaires). However, there is a growing body of evidence for a female predominance in constipation, bloating, and extra colonic manifestations while males appear to have diarrheal as the predominant feature.
Abdominal Pain and Discomfort
Recurrent abdominal pain is a diagnostic symptom of IBS, in addition to being the single most important determinant for both men and women in deciding to seek treatment for IBS. In one study, ‘‘belly pain’’ was reported by nearly two-thirds of all patients. Interestingly, neither the incidence of pain nor the severity of pain differed between male and female IBS patients. The prevalence of pain and discomfort is due to a heightened perception to colonic contents (visceral hypersensitivity), which is a characteristic finding in patients with IBS. However, current measures of enhanced visceral perception (e.g., decreased recto sigmoid pain thresholds) have not been consistently found in IBS patients and therefore are not currently used as a diagnostic marker.
Altered Bowel Habits
Altered bowel habits are a central feature of IBS. Patients are frequently classified as constipation-predominant, diarrheal-predominant, or alternating diarrheal and constipation. In a relatively large survey of male and female patients with IBS, Lee et al. found women nearly twice more likely to report constipation-predominant bowel habits, while men were more likely to report diarrhoea. This observation was reinforced in a community sample, in which Talley et al. similarly found women to be more likely to report constipation and males more likely to have diarrhoea. Several physiological factors may play a role in these sex-related differences in bowel habits, including differences in central autonomic control, and enteric nervous system and smooth muscle physiology. In addition, oestrogen and progesterone have been postulated to play a role in sex differences in bowel motility (see below).
Abdominal Bloating and Distension
Gas and bloating are frequently reported in both men and women with IBS. However, Lee et al. showed that women were significantly more likely than men to complain of bloating and furthermore to report it as their single most bothersome symptom. Several large community and clinic population studies have also confirmed gas, bloating, and distension to be more common among female IBS patients than among male patients. The cause of these symptoms is likely multifactorial, e.g., dietary factors, slowed transit of gas, and visceral hypersensitivity.
Extra colonic Symptoms
Although only colonic symptoms are used in the diagnostic criteria for IBS, patients frequently report extra colonic visceral and somatosensory symptoms. Functional dyspepsia (upper abdominal pain not associated with ulcer) affects 30%–60% of IBS patients and nausea and vomiting is reported in 25%–50% of patients with IBS. Women with IBS are especially prone to increased urinary frequency and urgency, which occurs in 65% of female patients with IBS and are often associated with abnormal urodynamic studies. Sleep disturbances also are more commonly reported by female IBS patients, although there has been some inconsistency in several studies to show abnormal plysomnographic parameters in IBS patients. Other extra colonic symptoms that have been found to be more likely in women than in men with IBS include alterations in taste and smell, muscle stiffness or aches, headache, back pain, and fatigue. Another important feature of IBS is its high coexistence with other functional pain disorders. Fibromyalgia and other rheumatological symptoms occur in over 60% of female IBS patients. Almost 40% of women with interstitial cystitis, a bladder condition characterized by suprapubic pain and urinary urgency or frequency, also have IBS. In addition, a chronic pelvic pain disorder is another important area of overlap with IBS. Several studies have shown a twofold higher incidence of dyspareunia in female IBS patients, as compared with female inflammatory bowel disease patients or male IBS patients.
The pathophysiology of IBS remains poorly understood, although there are several physiologic processes that appear altered in IBS: (1) alterations in the response of the gut to stimuli such as food (motor response), (2) an altered perception of a visceral stimuli (the afferent sensory pathway or the brain–gut axis), and (3) the perception of a no noxious visceral stimulus as noxious (psychological profile and altered cortical processing of visceral stimuli). Studies have clearly implicated various predisposing and trigger factors that are associated with the onset and exacerbation of IBS and these include genetic predisposition, chronic stress, and inflammation or infection. These factors may be associated with enhanced responsiveness of neural, immune, and neuroendocrine circuits along with brain–gut axis, resulting in altered bowel motility and visceral perception. The neuronal connection between the gut and the central nervous system (CNS) is referred to as the brain–gut axis. Evidence for Differences in Pathophysiology or Response to Treatment between Men and Women with Irritable Bowel Syndrome
It is not yet completely understood how the above model of disease can account for the sex differences observed in IBS. Few pathophysiological studies have focused on making sex comparisons, although there has recently been increased interest in this area. Numerous factors need to be considered in the exploration of these differences. These factors include biologic, hormonal, behavioural, psychosocial, and psychophysiological mechanisms of IBS, including any sex-specific finding noted in the literature.
Post infectious IBS
It has long been recognized that IBS-like symptoms may develop in a minority of patients recovering from enteric infection. Up to 17% of all patients with IBS will report their symptoms following an episode of gastroenteritis. Between 7% and 30% of patients recovering from proven bacterial gastroenteritis IBS symptoms have been reported to develop. Organisms that have been associated with post infectious IBS include Salmonella, Campylobacter jejune, and Shigella.
Effect of Oestrogen or Progesterone
Impaired gall bladder contraction to progesterone
Decreased lower oesophageal sphincter pressure in pregnancy
Visceral afferent pathway
Modulation of response of afferent neurons to substance P (guinea pig)
Lower threshold for viscometer response in the proestrus compared with oestrus phase of oestrus cycle in rats
Cytochrome P450 pathway is affected by oestrogens and progesterone
Animal studies Pain pathways
Oestrogen effect is complex and oestrus cycle dependent
Greater potency of opiates to decrease viscometer response in male compared with female rats
Slower gastric emptying in women compared with men
Response to colonic distention
Conflicting reports of the effect of the menstrual cycle on pain sensation to colorectal distention
Different areas and intensity of brain activation in response to colorectal distention in men and women
Somatic pain response
Greater score on a catastrophizing scale in women compared with men
Neurotransmitter uptake pathway
Altered GI Motility
Given the predominance of altered bowel habits, abnormal gut motility has long been considered a leading etiologic factor of IBS. However, objective findings of motility alterations have been inconsistent, with no distinct pattern distinguishing IBS patients from healthy controls. Two major observations that have been observed are increased gut transit time in some patients with constipation-predominant IBS and decreased transit time in those with diarrhoea-predominant IBS. In addition, several studies have shown that IBS patients have increased motility compared with healthy subjects to a variety of stimuli, including psychological stress, meals, and balloon inflation in the gut. Overall, males have shorter intestinal and total GI transit times than their female counterparts. These differences in colon transit and motility may explain the greater vulnerability of developing constipation in women compared with men.
Enhanced perception of visceral stimuli has emerged as an important model IBS pathophysiology and an area of intense GI research. Multiple studies using colonic or rectal balloon distension paradigms have consistently demonstrated lower discomfort thresholds in IBS patients compared with controls. Differences in visceral sensitivity between men and women with IBS have not been studied extensively, though evidence thus far shows that women may be more prone to develop hypersensitivity, especially following repeated stimuli. In a study of 52 IBS patients (39 females and 13 males), Ragnarsson et al. found a significant decrease in postprandial rectal thresholds (mmHg) of maximal tolerated distension in women compared with men (i.e., increased rectal sensitivity in women compared with men). There were no significant gender differences in symptoms. Another study assessed the presence of sex differences in rectal discomfort thresholds before and after noxious sigmoid distensions in 26 healthy individuals (9 males, 17 females) and 58 IBS patients (34 males and 24 females). Rectal discomfort thresholds were significantly lower in IBS females compared with IBS males, following noxious stimuli. In addition, though female control subjects had higher rectal discomfort thresholds than IBS females, a significant proportion of both groups demonstrated a decrease in thresholds after noxious sigmoid stimulation.
Altered Central Mechanisms
Recent findings in functional neuroimaging studies support the hypothesis that dysregulation of the brain–gut axis plays a key role in IBS. Differences in the activation of several brain regions have been demonstrated and include the anterior and midcingulate cortices, insula, and dorsal pons, which are some of the most consistently activated brain areas in response to visceral as well as somatic nociceptive stimuli. These regions are concerned with cognitive and affective aspects of processing of sensory input, including noxious stimuli. These observations suggest that IBS patients have altered central pain modulatory pathways in response to incoming or anticipated visceral pain. Two studies have examined sex differences in the brain responses to colorectal distension in IBS. Berman et al. reported significantly greater activation of the insula bilaterally in male IBS patients compared with female IBS patients. Naliboff et al. found that men with IBS had greater activation in areas associated with the cognitive processing of painful sensations, including the insula and midcingulate cortex, while women with IBS showed greater activation in limbic regions, including the amygdala and infragenual cingulated cortex, which are associated with the emotional processing of visceral stimuli.
With women in general, GI symptoms appear to be influenced by female sex hormones; with both upper and lower GI symptoms increasing during the late luteal and early menses phases relative to the follicular phase. The effect of menstrual cycle on IBS has been described by several investigators. In one survey, 50.8% of patients reported a worsening of their IBS symptoms at the time of menses. Women with IBS were also found to rate stomach pain, nausea, and diarrhoea, but not somatic complaints like backache, as more severe at menses than healthy female subjects, suggesting enhanced visceral sensitivity during the premenstrual period. Other symptoms commonly associated with menstrual cycle function, such as breast tenderness, bloating, and affective symptoms, were found to be elevated in IBS patients across all cycle phases, with a similar increase in severity immediately prior to or at the onset of menses. The effect of menstruation on IBS symptoms is thought to be mediated by ovarian hormones affecting bowel function either centrally or peripherally. This is supported by the finding that during pregnancy, a time of very high oestrogen and progesterone levels, GI symptoms (nausea, constipation, upper GI distress) increase and intestinal transport decreases. In addition, IBS patients on oral contraceptives that mimic naturally fluctuating ovarian hormones will continue to have amplification of their GI symptoms during menses. Finally, Houghton et al. found that women with IBS had greater rectal sensitivity during menses than other points during menstrual cycle. It is noteworthy that no menstrual cycle phase differences were found in rectal compliance, wall tension, or motility. Interestingly, in addition to a higher prevalence of visceral pain in women patients during the premenstrual phase, the diagnosis of IBS is threefold more common in women with dysmenorrhoeal (painful menstruation) than in those without. A similar co-morbidity between dysmenorrhoeal and fibromyalgia has been suggested. These findings further support the existence of a more generalized alteration in the perception of visceral and somatic pain in a subset of IBS patients.
While recognizing that biologic sex differences exist between male and female IBS patients, Toner and Akman have provided insights into gender-related differences in how symptoms might be experienced and interpreted. They suggest the concept of gender role, which is defined as generalizations about male and female traits that are associated with masculinity and femininity. However, there is a lack of available data on how these gender-specific themes participate in a syndrome such as IBS with respect to its physiologic characteristics such as motility, pain sensitivity, and autonomic function.
Effect of Gender on Psychological Response to Pain: Impact of Abuse History
Subsequent studies confirm the greater prevalence of these psychological traits, but the female gender appeared to be less of a risk factor. In light of the reported predisposing risk factor of infection and the report of a greater number of mucosal mast cells in the colon of subjects with IBS, it is of interest that there are more constitutive mast-cell populations in the jejunum and colon in female rats compared with male rats. Whether any similar difference is seen in humans is unknown.
Given the multiple factors that are altered or contribute to the pathogenesis of IBS, the treatment of this complex disorder requires a bio psychological approach. This multidimensional approach addresses the biology of IBS as well as the psychological and social factors that are common among affected individuals. A detailed patient history that includes a comprehensive review of the patient’s social and psychiatric history is the first step in establishing a treatment plan. The biopsychosocial approach demands more face-to-face patient time and may not be widely available. This may account in part for why only 49% of patients with IBS report a response to medical treatment. Efficacy of specific treatment modalities often is difficult to establish because of the high placebo effect associated with interventions used to treat IBS. It is not surprising that over 50% of IBS patients in an outpatient setting report the use of alternative therapies. It is not the purpose to review every therapy currently available for IBS, but to highlight those whose efficacy, use, or availability are affected by sex or gender.
Recently, the emergence of new IBS-specific medications has revealed the potential importance of sex-based differences in this disease. Aldosterone, a selective 5-HT3 receptor antagonist, has been FDA approved for use in women with severe diarrheapredominant IBS. Early clinical trials suggested that aldosterone had a greater efficacy in females than in males. The greater efficacy in women may be in part due to the greater change in overall colonic transit in women than in men with IBS. However, there was a more recent study demonstrating that aldosterone is effective in men with diarrhoea-predominant IBS with respect to adequately relieving abdominal pain and discomfort and improving stool consistency. But there was no significant improvement in stool consistency and urgency with alosetron compared with placebo. The authors postulated that the observed differential treatment effects may be related to a combination of sex-based differences in peripheral as well as central mechanisms. Similarly, tegaserod, a 5-HT4 receptor partial agonist, was initially indicated only for female IBS patients with constipation as their primary bowel symptom. However, tegaserod was also recently shown to be effective for the treatment of chronic constipation in men and women and is newly approved for this indication. The initially demonstrated sex difference in response to these serotonergic agents may have been due to the fairly small numbers of males studied in the clinical trials. While there may be some small differences in treatment response to these agents, further studies are needed to substantiate gender differences.
In a 1997 survey, 42% of the US population has reported the use of complementary medicine and other studies have indicated that more women than men use such therapy. Most individuals wish to use complementary medicine concurrently with conventional approaches. The reasons why IBS and functional dyspepsia patients report using complementary medicine were dissatisfaction with conventional medicine, a desire to treat digestive symptoms with a more natural approach, to determine whether alternative therapies might help to alleviate the problem, or that complementary medicine was recommended by another individual. The no pharmacological approaches to the treatment of IBS that have been shown to have documented efficacy are listed. At this time, there are five no pharmacological approaches to the treatment of IBS: relaxation alone, hypnotherapy, short-term psychodynamic psychotherapy, cognitive–behavioural combination therapy, and pure cognitive therapy. These therapeutic modalities can be considered in IBS patients with moderate to severe symptoms, when patients have failed medical treatments, or when there is evidence of stress or psychological factors that contribute to GI symptom exacerbation. While many of these studies included men and women, gender differences were not usually determined. The only exception is hypnotherapy, which in a recent study was found to be associated with greater overall improvement in IBS symptoms in females compared with males (52% vs. 33%). Supplementation with herbal preparations have yielded mixed results except for STW-5 (which is a composite of nine Chinese herbs), standard forms of traditional Chinese medicines, peppermint oil, and artichoke leaf extract, which have proven benefits for IBS. Melatonin at 3 mg=day was studied specifically in females with IBS.
Summary of Complementary and Alternative Medicine in Irritable Bowel Syndrome
Herbs Mind–Body: Best Results
Peppermint oil (p-IBS) (8 studies, benefit) Psychological
TCM (d-IBS), STW-5 (benefit) Cognitive behavioral treatment
Elimination diet (15%–71% response, no sustained) Reflexology
Supplements Guided imagery
Melatonin (1 study, benefit) Meditation
Probiotics 8 RCT’s (7 benefit) Biofeedback
Acupuncture (2 controlled sham studies 2 benefit) Multicomponent
TCM, Traditional Chinese medicine; STW, (name of herbal preparation); RCT, randomized controlled trial.
Melatonin is involved in seroterogenic regulation in the gut and thus was studied specifically in females, because serotonin-modifying drugs work best in females. Lu et al. demonstrated that women taking 3 mg of melatonin=day for 8 weeks had significant reductionsin global symptoms and pain compared with placebo. These therapeutic modalities can be considered in IBS patients with moderate to severe symptoms, when patients have failed medical treatments, or when there is evidence of stress or psychological factors that contribute to GI symptom exacerbation. The concept that intestinal flora could be responsible for bloating and gassiness associated with IBS was recently bolstered by reports that up to 80% of IBS patients have small intestinal bacterial over growth. Other investigators have not been able to substantiate an incidence this high perhaps in part due to the insensitivity of breath hydrogen testing available in most hospitals or centres. A 10 day course of Rifaximin, a no absorbable antibiotic, resulted in greater improvement of bloating in IBS patients overaperiodof10weeksaftertherapy, due to methodological issues. It has long been speculated that alterations in the normal colonic flora might abate the symptoms of IBS for several reasons. Probiotics, which are ingested substances containing live organisms that have a beneficial effect on the host by altering the body’s intestinal microflora, may help to eliminate intestinal pathogens, alter motility, and reduce bacterial fermentation and pathogen-related inflammation. Improvement in bloating and flatulence has been reported from several small studies. Organisms that have been associated with improvement include L. plantarum, B. infantis, and Bifidobacterium. While there has been limited evidence of gender differences in response to no pharmacological treatment, the authors recommend that careful attention to gender issues be given when choosing and providing treatment for IBS patients. Such gender-specific issues were discussed earlier and include history of physical and sexual abuse, gender role socialization or conflict, and perfectionist views of bodily function or image. Mind–body therapies with established efficacy include relaxation, yoga, hypnotherapy, short-term psychodynamic psychotherapy, guided imagery, cognitive–behavioural combination therapy, and pure cognitive therapy.
Treatment of IBS always involves manipulation of the diet, as it is well known that withdrawal of certain dietary substances can improve IBS symptoms. Foods typically associated with gas production are notorious for provoking IBS symptoms. These include foods rich in fermentable carbohydrates such as beans and cabbage, and foods containing large concentrations of fructose, sorbitol, and lactose. Some IBS patients will report worse bloating after ingesting rich meals, which may be explained by the observation of increased small intestinal gas retention with direct infusion of dietary fat into the small intestine. Agents that stimulate colonic motility may precipitate abdominal pain in IBS patients, thus it is generally recommended that IBS patients with bloating, pain, or diarrhoea eliminate foods and beverages containing caffeine, a known colonic stimulant Increasing dietary fibre, which is often prescribed as first line therapy for the treatment of IBS because it tends to regulate bowel movements, may also exacerbate IBS symptoms because fibre is not absorbed; indeed, in one study 50% of IBS patients reported an exacerbation of symptoms and only 11% reported an improvement. Both soluble and insoluble dietary fibre are fermented by intestinal flora to produce short-chain fatty acids and gas. A feature of IBS is visceral hypersensitivity to gas distention of the gut, and hence, the association of dietary fibre with increased bloating and gas. Food hypersensitivities and food intolerances found in IBS patients may also trigger IBS symptoms. Food hypersensitivity, or food allergy, is defined as an immunological response to food proteins and is characterized by alterations in serum antibodies or cellular immunity. The mechanisms responsible for food allergy are now beginning to be discerned and may greatly impact future IBS therapy. Food intolerance on the other hand refers to carbohydrate malabsorption; malabsorption of lactose, fructose, fructans, and sorbitol can produce bloating, abdominal pain, and diarrhoea in both IBS patients and normal controls. It is unknown if the prevalence of food allergy is truly greater in IBS patients compared with normal controls, although 60% of IBS patients suspect they have a food allergy. However, the role of food allergy in IBS symptoms remains unclear since food allergy only affects 4% of American adults. The notion that food allergens could precipitate IBS symptoms is particularly attractive since mast cells and their mediators alter visceral hypersensitivity and gut motility. Food allergy may be separated into non-IgE- (cellular) or IgE-mediated reactions.
In the worst clinical scenario, food allergies can produce gut anaphylaxis, characterized by acute nausea, vomiting, colicky abdominal pain, and allergic manifestations in other organs. Allergies to peanut, tree nuts, fish, and shellfish account for most adult food allergies. Eosinophilic gastroenteritis, which may be IgE- or non-IgE-mediated, features an eosinophilic infiltration of the GI mucosa and may arise in individuals with atopy or food allergies. Symptoms associated with eosinophilic gastroenteritis depend on which organ is involved, but may include heartburn, nausea, abdominal pain, and vomiting. A classic example of a non-IgE-mediated allergy is celiac sprue, a disorder of malabsorption caused by an allergy to gluten, a protein found in many grains, including wheat. Celiac sprue has been reported in as many as 20% of IBS patients but this figure has been disputed. Some IBS patients may describe an intolerance to wheat, but this ‘‘intolerance’’ is distinct from a true allergy to gluten. An improvement in symptoms in response to wheat avoidance is often mistakenly interpreted by the patient as evidence that he or she has underlying celiac sprue. The diagnosis of celiac sprue, is more strongly suggested by endoscopic biopsy demonstrating villous flattening and intraepithelial lymphocytosis in the small bowel mucosa in addition to circulating serum IgA antibodies to tissue transglutaminase. The diagnosis is ultimately established by demonstrating histologic improvement in response to gluten withdrawal from the diet. Diagnosing food allergy is a clinical challenge because tests with a high positive predictive value are still lacking. For example, skin prick testing is used extensively, but a positive result does not prove that a specific food is responsible for symptoms. Radioallergosorbent testing (RAST) to identify serum IgE antibodies against potential food allergens has also been proposed; although negative results are effective for ruling out an IgE-mediated reaction to a specific food allergen, the positive predictive value of a positive RAST result is also low. The utility of measuring serum IgG titers has been controversial as well because such food antibodies are common and may even be physiological. But because serum IgG4 and IgE antibodies have been implicated in atopic conditions induced by food hypersensitivity, such as atopic dermatitis, hay fever, and asthma, Zar et al. sought to determine the clinical significance of IgG4 titers to common food antigens in 108 IBS patients and controls.
Although they found that serum IgG4 titers to wheat, beef, pork, lamb, and soy bean were higher in IBS patients than in controls, there was no correlation between the titer and degree of symptoms. No significant difference in titers to potatoes, rice, fish, chicken, yeast, tomato, and shrimp was observed. Moreover, in this study no significant difference was observed in IgE antibody response to food antigens or to cutaneous pin-prick testing. These results led the authors to perform another study in which food-specific IgG4 antibody titers >250 mcg=L were used to develop 6 month exclusion diets that improved IBS symptoms and rectal compliance in a small group of patients. Further studies are necessary to elucidate the significance of IgG4 titers in predicting food hypersensitivities. In the absence of tests with high positive predictive values, the double blind, placebo-controlled food challenge remains the gold standard for the clinical diagnosis of food allergy. After a 2 week withdrawal of suspected food allergens from the diet, encapsulated food substances or placebo are given to patients who are then monitored for symptoms. Most practitioners instead favour the less-cumbersome elimination diet in which symptoms are monitored after potential offenders are withdrawn from the diet for 4–6 weeks and then later reintroduced. The first report that an exclusion diet improved IBS symptoms in a small group of 21 IBS patients was published in 1982. In Niec’s 1998 review of seven studies to determine whether adverse food reactions played a role in IBS symptoms, a positive response to an elimination diet ranged from 15% to 71%. Studies based on subjects with diarrhoea-predominant IBS tended to find improvement with elimination diets.
The most common offenders were milk, wheat, and eggs, but it should be noted that no included study was free from methodological limitations. Like food allergy, the diagnosis of food intolerance to carbohydrates is difficult to make given the limitations of current testing. Intolerance to lactose, fructose, fructans (polymerized form of fructose), or sorbitol may contribute to symptoms characteristic of IBS, such as bloating, gassiness, abdominal pain, and diarrhoea. Fructose malabsorption leads to the delivery of unabsorbed fructose to the colon where it is fermented by intestinal bacteria to produce gas that can be associated with bloating and abdominal pain. The diagnosis is currently established by breath hydrogen testing, but unfortunately this test is fraught with technical limitations and not well standardized among labs. It appears that fructose, lactose, and sorbitol malabsorption appear to be equally prevalent in healthy volunteers. Hereditary fructose intolerance, due to a deficiency in fructose-1, 6-bisphosphate aldolase, is rare and present in infancy. Thus, most fructose malabsorption may result from a diet high in fructose that overwhelms the absorptive capacity of the normal small intestine, or possibly small bowel bacterial overgrowth in which intestinal bacteria ferment fructose to produce hydrogen gas. It is not certain what is the average consumption of fructose in the daily American diet, but it is likely to be higher than the average 37 g consumed in 1977–78 as a result of the introduction of high fructose corn syrup as a widespread food additive over the past 30 years. It has been estimated that the consumption of high fructose corn syrup has increased more than 1000% in the 20 years spanning 1970–90. Despite the lack of difference in prevalence in carbohydrate malabsorption, IBS patients may report symptomatic improvement upon withdrawal of fructose, fructans, sorbitol, and lactose. When IBS patients who had fructose malabsorption identified by breath hydrogen testing were given dietary instruction to limit foods containing free fructose and short-chain fructans, reduce dietary fructose load, and to consume foods in which glucose was balanced with fructose, 85% of those adherent to the diet reported symptomatic improvement compared with only 36% who deviated from the diet.
CONCLUSIONS AND FUTURE RESEARCH
IBS is an extremely common GI condition for which there is increasing evidence for sex and gender differences, not only in prevalence, but also in clinical presentation, pathophysiology, and treatment response. Although there exists a gender bias in diagnostic criteria and rates of general health care utilization, IBS appears to occur in females at about twice the rate of men. While rates of abdominal pain are similar, female IBS patients report more constipation, bloating, and extra intestinal viscero- and somatosensory symptoms and pain disorders. Both IBS and non-IBS symptoms appear to be influenced by menstrual cycle, presumably through ovarian hormones affecting central and peripheral sensitization. Although there is some evidence that sex and gender differences in treatment response may exist, large clinical trials with sufficient numbers of men and women with IBS are needed to determine if these differences for a specific treatment truly exist. The physiological basis for the above sex differences in this syndrome is still unclear. There is a growing amount of experimental data that suggest that females may have slower GI transit, exhibit a greater tendency to develop visceral hypersensitivity and post infectious IBS, and have greater activation of limbic brain regions in response to visceral stimulation than males. Future well-designed studies incorporating sufficient numbers of both males and females with IBS will hopefully lead to a more comprehensive understanding of sex and gender differences in IBS. Other alternatives for treatment and dietary management of IBS, particularly in women, should continue to be explored.