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Jointly sponsored by the Dannemiller Memorial
Educational Foundation and The Customer Link, Inc.
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A CME/CPE/CE Activity
This activity is supported by an educational grant from
Sucampo Pharmaceuticals, Inc. and Takeda Pharmaceuticals North America, Inc.
Release date: July 2008
Expiration date: July 31, 2009
Introduction
IBS, a chronic condition characterized by
abdominal pain and altered bowel function,
affects approximately 58 million people in
the United States. The prevalence of IBS and
other functional bowel disorders is far higher in
women than in men, with 80% of IBS sufferers
being women between the ages of 20 and 40.
Despite the fact that IBS predominantly
affects women, current diagnostic criteria do
not address the particular issues specific to
women. IBS diagnoses can be challenging
since many symptoms overlap with those of
other functional bowel disorders, specifically
chronic constipation, and other conditions.
With recent advances in definition, updated
guidelines, and continuous studies, researchers and clinicians have tried to delineate the
differences between chronic constipation and
IBS in order to provide better clinical care for
both of these often-overlooked disorders.
Once an IBS or chronic constipation diagnosis is confirmed, a successful treatment
plan must be established. Due to the everchanging scope in diagnosis and treatment, it
is important for clinicians to stay up-to-date
on emerging data in IBS and chronic constipation. This monograph will provide insight
related to IBS and chronic constipation diagnosis and management in women.
Learning Objectives
• Describe the signs and symptoms of IBS
in women and differentiate IBS from other
functional bowel disorders
• Identify gender differences and other conditions associated with IBS in women
• Cite the American College of Gastroenterology guidelines for diagnostic testing in
patients with IBS
• Assess the usefulness of lifestyle modifications and alternative treatments in the
management of IBS
• Review the current pharmacologic treatment options used to manage IBS and other
functional bowel disorders and explore their
mechanisms of action
Target Audience
This activity is designed for clinicians with
an interest in the diagnosis and treatment of
IBS in women.
Method of Participation
This activity should take approximately 1 hour
to complete. You should read the objectives and
other CME information, then proceed through
the monograph. To receive CME/CPE/CE credit,
please visit http://totalmeded.com/ibsmonograph.
The evaluation on the posttest site provides you
with the opportunity to comment on the extent
to which the educational needs were met, the
quality of the instructional process, the perception of commercial bias, and your view on
future educational needs.
This credit is available through July 31,
2009. No credit will be given after this time.
Accreditation and Designation
Physicians: This activity has been planned
and implemented in accordance with the
Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the
Dannemiller Memorial Educational Foundation and The Customer Link, Inc. The
Dannemiller Memorial Educational Foundation is accredited by the ACCME to
provide continuing medical education for
physicians.
The Dannemiller Memorial Educational
Foundation designates this educational activity for a maximum of 1 AMA PRA Category
1 Credit(s)™. Physicians should only claim
credit commensurate with the extent of their
participation in the activity.
Pharmacists: Purdue Uni-
versity School of Pharmacy and Pharmaceutical
Sciences is accredited by the Accreditation
Council for Pharmacy Education as a provider of continuing pharmacy education. This
program is a continuing education activity
of Purdue University, an equal access/equal
opportunity institution. Universal Program
Number (UPN): 018-999-08-107-H01-P, 1.0
contact hours (.10 CEU). Release date: July
2008. Expiration date: July 31, 2009.
Nurse Practitioners: This program has been
approved for 1.0 contact hours of continuing education (which includes 0.5 hours of
pharmacology) by the American Academy of
Nurse Practitioners. Program ID 0805234.
Nurses: The Dannemiller Memorial Educa-
tional Foundation is an approved provider of
the California Board of Registered Nursing.
Provider Number 4229 for 1.2 contact hours.
RNs outside California must verify with their
licensing agency for approval of this course.
Physician Assistants: AAPA accepts 1 credit
from AOACCME, Prescribed credit from
AAFP, and AMA Category 1 CME credit for
the PRA from organizations accredited by
the ACCME.
Faculty
David A. Peura, MD, MACG, FACP
University of Virginia Health
Sciences Center
Charlottesville, VA
Suzanne Rose, MD, MSEd
Mount Sinai School of Medicine
New York, NY
Disclosures
In accordance with the Accreditation Council for
Continuing Medical Education (ACCME), the
Dannemiller Memorial Educational Foundation
requires that any person who is in a position
to control the content of a CME activity must
disclose all relevant financial relationships they
have with a commercial interest. Accordingly:
Dr. Peura reported that he serves as a
speaker for, consultant to, and member of the
advisory board for Takeda Pharmaceuticals
North America, Inc. and TAP Pharmaceutical Products Inc. Dr. Peura also reported that
he serves as a speaker for AstraZeneca and
Santarus, Inc.
Dr. Rose reported that she serves as a
speaker for, consultant to, and member of the
advisory board for Takeda Pharmaceuticals
North America, Inc. and Sucampo Pharmaceuticals, Inc. Dr. Rose also reported that she
serves as a speaker for TAP Pharmaceuticals
Products Inc.
Jason Jenkins, medical writer, and Pete
Sloan, medical editor, have no financial relationships with any commercial interests that
are relevant to disclose.
The Dannemiller staff and Customer Link
staff that were involved in the development
of this activity have no financial relationships with any commercial interests that are
relevant to this activity.
To resolve identified conflicts of interest, the educational content was fully peer
reviewed by a physician member of the
Dannemiller Clinical Content Review Committee who has nothing to disclose. The
resulting certified activity was found to provide educational content that is current, evidence-based, and commercially balanced.
Disclosure of Unlabeled or
Investigational Drugs
This educational activity may contain discussion of published and/or investigational uses
of agents that are not indicated by the FDA.
The opinions expressed in the educational
activity are those of the faculty.
Please refer to the official prescribing
information for each product for discussion
of approved indications, contraindications,
and warnings. Further, attendees/participants
should appraise the information presented
critically and are encouraged to consult
appropriate resources for any product or
device mentioned in this program.
Disclaimer
The content and views presented in this
educational activity are those of the authors
and do not necessarily reflect those of The
Dannemiller Memorial Educational Foundation; Takeda Pharmaceuticals North America, Inc.; or The Customer Link, Inc. This
material is prepared based upon a review of
multiple sources of information, but it is not
exhaustive of the subject matter. Therefore,
healthcare professionals and other individuals should review and consider other
publications and materials on the subject
matter before relying solely upon the information contained within this educational
activity.
To take the posttest and receive CME/CPE/
CE credit, please visit the following Web site:
http://totalmeded.com/ibsmonograph.
This activity is supported by an unrestricted educational grant from Sucampo Pharmaceuticals, Inc.
and Takeda Pharmaceuticals North America, Inc.
Jointly sponsored by the Dannemiller
Memorial Educational Foundation and
The Customer Link, Inc.
Conquering IBS in Women: The Clinician’s Pursuit of Optimum Management Strategies
Women: Bearing the Burden of IBS
with IBS reported being too sick to work or go to school than
did those without IBS (11.3% vs 4.2%).
Furthermore, IBS often goes unrecognized, undiagnosed,
and/or untreated, and many patients often endure symptoms
for months or years before consulting a health care provider.13
A survey of 340 IBS patients (276 of whom were women)
found that 42% of respondents had been diagnosed with IBS
≥10 years before the survey; almost two-thirds had had the
condition for at least 5 years.
Irritable bowel syndrome (IBS) has been defined as a functional bowel disorder in which abdominal pain or discomfort
is associated with defecation or a change in bowel habit, along
with features of unsatisfactory defecation.1 Characterized by
cramping, abdominal pain, bloating, constipation, and/or diarrhea, IBS is one of the most common gastrointestinal (GI)
disorders diagnosed in the United States, with a prevalence of
approximately 15% to 20%.2 Symptoms associated with the
disorder occur frequently, resulting in considerable physical,
emotional, and economic costs.
Women bear much of the burden of IBS: twice as many
women as men seek treatment for IBS in the United States and
other Western countries.3,4 Whether the increased prevalence in
female patients means that women are more willing than men
to report IBS-related symptoms, or if it means that women are
biologically predisposed to IBS, is still not clear; however, it is
worth considering that functional pain syndromes with a female
predominance (fibromyalgia, chronic fatigue syndrome, interstitial cystitis, and migraine headaches) overlap with IBS.5
Recent data also suggest that gender differences exist
in the symptoms, pathophysiology, and response to certain
treatments in IBS.6 Female IBS patients are more likely to be
constipated and complain of abdominal distension and extraintestinal symptoms.
The purpose of this review is to highlight the issues facing
women with IBS, including proper management and treatment
options.
IBS: Pathophysiology
IBS is a chronic, relapsing, and frequently lifelong condition
of unknown etiology14; however, abnormalities of GI visceral
sensation, motility, autonomic function, bacterial flora, and
immunity have been cited as possible mechanisms accounting
for symptoms.15 IBS may also be regarded as a collection of
symptoms without a single cause that reflects an integrated
response to a variety of complex biologic and psychosocial
factors.16 In other words, IBS may be seen as a disorder of
brain-gut interactions with both physical and psychosocial
components.16,17 Figure 1 illustrates a proposed pathophysiologic model of IBS.18
Figure 1. IBS: Pathophysiology18
The Cost of IBS
IBS exacts a significant economic burden. A 2007 study of 558
IBS patients revealed that the mean annual direct health care
costs were $5049 per patient for IBS, and the annual average
out-of-pocket expenses to treat this condition were $406 per
patient.7 Health care costs of IBS and associated productivity
losses attributed to IBS symptoms are approximately $30 billion annually,8 comparable to the costs associated with asthma,
migraine, or hypertension.9-11
Chang and colleagues found that women with IBS had
a lower quality of life and reported more fatigue, depressed
mood, and levels of anxiety, and less positive self-control and
well-being compared with men with IBS.5 Furthermore, Lee
and colleagues compared health-related quality of life scores
between men and women with IBS and found that female
patients with IBS had worse raw scores than did male patients;
however, after controlling for gender differences in the general
population, the only disparity was greater bodily pain scores in
the female patients.4
The symptoms of IBS often affect a patient’s ability to live
a fulfilling life. This was demonstrated by Drossman and colleagues, who showed that patients with IBS had missed about
3 times as many days from work or school in the previous year
because of illness as did those with no evidence of functional
GI disorder (mean values, 13.4 vs 4.9 days; P=.0001).12 The
same study revealed that a higher proportion of individuals
The etiology and role of motility anomalies in IBS patients are
unknown; however, researchers have long believed that distorted motility patterns of the rectum, colon, and small bowel
are the primary reason for the abdominal pain experienced
by IBS patients.19 Although the motility response to various
stimuli (eg, diet, psychological distress, or physical activity) is
similar in IBS patients and healthy controls, there are measurable differences in the degree of response.20 Patients with IBS
have increased motor reactivity, which may be perceived as
pain or discomfort. Factors such as meals, stress, cholecystokinin secretion, and neostigmine or corticotropin-releasing
hormone injection can increase motor activity in the ileum,
colon, and rectum in these patients.
Another important consideration is gender differences in
gut transit duration because women have slower gut transit
Conquering IBS in Women:
Women: The
The Clinician’s
Clinician’s Pursuit
PursuitofofOptimum
OptimumManagement
ManagementStrategies
Strategies
times than do men.5 Whether this difference is a function of
the menstrual cycle remains unclear.
Studies involving balloon distension of the bowel have confirmed that visceral hypersensitivity (enhanced perception of visceral events and a lower threshold for pain) occurs in IBS patients,
confirming a brain-gut interaction.21 There are also gender differences in processing visceral perception in IBS patients. Whereas
male IBS patients show greater activation of cognitive areas,
activation of central sympathetic areas, and inhibition of limbic
regions of the brain in response to visceral stimulation, female
IBS patients display greater activation of affective (emotional)
and autonomic regions of the central nervous system.22 These differences could explain gender-related differences in autonomic,
emotional, and antinociceptive and treatment responses.
Appreciating brain-gut interactions is a key to understanding
and treating IBS. Research on the role of neuroendocrine and
sex-linked hormones in the autonomic nervous system and
pain modulation might help explain the variation and severity
of IBS symptoms experienced by some women during their
menstrual cycles.
Painful Menstruation
The influential role of ovarian hormones such as estrogen and
progesterone on bowel function and pain sensitivity may help
explain the gender differences in IBS.5 GI symptoms increase
throughout the entire menstrual cycle, especially during the
late luteal and early menses stages.5 Several investigators have
observed this variation in GI symptoms throughout the menstrual cycle—particularly, increased abdominal pain and loose
stools just before and at the onset of menstruation.
In a 2003 study of female IBS patients aged 18 to 48 years,
Heitkemper and colleagues found that women in the IBS-C and
IBS with mixed bowel pattern (IBS-M) groups reported more GI
symptoms and showed a trend toward having more symptoms of
all types compared with those in the IBS with diarrhea (IBS-D)
group.26 These symptoms were significantly affected by menstrual cycle phase. Heitkemper concluded that premenstrual
syndrome is more common in women with IBS, especially
those with IBS-C and IBS-M, and that dysmenorrhea is twice
as prevalent in women with IBS as in those without IBS.
IBS Subtypes
Patients with IBS can be categorized into 4 groups based on
bowel patterns and response to treatment (Table 1).1,23
Table 1. IBS Subtypes1,23
IBS Subtype
Characteristics
IBS-C
• Hard stools ≥25% of the time
• Loose stools <25% of the time
• More common in women
IBS-D
• Hard stools <25% of the time
• Loose stools at ≥25% of the time
• More common in men
IBS-M
• Both hard and soft stools ≥25%
of the time
Unsubtyped IBS
• Stool consistency not sufficiently abnormal to meet criteria for IBS-C, IBS-D, or IBS-M
History of Abuse
IBS is one of many different functional somatic syndromes
characterized by persistent bodily complaints for which examination does not reveal a specific pathology. Consequently,
clinicians managing IBS patients, especially women, should
consider the patient’s history and realize that treating IBS
might require a multidisciplinary approach.
The link between sexual, physical, verbal, and emotional
abuse and functional GI symptoms has been well established.
In 1995, Drossman and colleagues found that patients with a
history of sexual abuse were 2.8 times more likely to have a
functional bowel disorder.27 One study concluded that 31% of
IBS patients reported some form of abuse, and another investigation revealed that 44% of female GI patients had a history of
sexual or physical abuse. Furthermore, women with functional
GI symptoms are 3 to 4 times more likely than men with similar complaints to report a history of abuse.27
IBS, irritable bowel syndrome; IBS-C, IBS with constipation; IBS-D, IBS with diarrhea;
IBS-M, IBS with mixed bowel pattern.
IBS with constipation (IBS-C) and chronic constipation
share several symptoms, such as straining, hard or lumpy stools,
decreased bowel movement (BM) frequency, and the sensation
of incomplete evacuation.24 What distinguishes IBS-C from
chronic constipation is the presence of abdominal pain.24,25 Individuals exhibiting little or no abdominal pain are more likely to
have chronic constipation, whereas those experiencing abdominal discomfort are more likely to have IBS-C.
Postinfectious IBS
In postinfectious IBS (PI-IBS), low-grade GI inflammation
or immune activation may result in altered motility. Approximately 10% of individuals with acute gastroenteritis will
develop chronic IBS-like symptoms; PI-IBS caused by Campylobacter, Shigella, or Salmonella can occur in 7% to 31% of
these patients.28 Increasing duration of initial infection-associated symptoms is the strongest risk factor for the development
of PI-IBS; symptoms lasting more than 3 weeks can increase
the risk of developing PI-IBS 11-fold.
Conditions Associated With IBS in Women
An important clinical feature of IBS, especially in women,
is its overlap with other GI disorders, non-GI pain disorders,
and affective disorders. The autonomic nervous system plays
a critical role in IBS through both visceromotor responses
and effects on pain modulation.6 It has been postulated that
psychological and neurobiologic mechanisms account for
IBS symptoms as do observed gender-related disparities.
Recent findings note that stressful life events occurring
immediately before or after acute infection are also a precursor
of IBS development, especially in women. One study examining equal numbers of men and women with gastroenteritis
revealed that IBS symptoms were present at 3 months after a
stressful life event in 77% of the female cohort versus 36% of
the male cohort.6
nosis. Other symptoms supporting a diagnosis of IBS are an
abnormal frequency of BMs (<3 BMs per week or >3 BMs
per day), abnormal stool form (lumpy/hard, loose/watery),
straining, urgency, sensation of incomplete stool evacuation,
presence of mucus in the stool, and bloating. Figure 2 shows
the diagnostic criteria for IBS.1
Figure 2. Rome III Diagnostic Criteria* for IBS1
Fibromyalgia and Other Symptoms
More than 60% of female patients with IBS complain
of fibromyalgia and other rheumatologic symptoms.6
Other conditions reported more often in patients with
IBS than in the general population include hypertension, headaches, low back pain, insomnia, nonspecific
fatigue, and palpitations.
Recurrent abdominal pain or discomfort
at least 3 days/month in the last 3 months
associated with 2 or more of the following:
Chronic Pelvic Pain
Chronic pelvic pain occurs in 35% of women with IBS.6
Women with both pelvic pain and IBS are more likely
than those with IBS alone to have a lifetime dysthymic
disorder or panic disorder or a history of sexual abuse.
Women with both pelvic pain and IBS are also more
likely to undergo a hysterectomy.
Improvement
with defecation
Onset
associated with
a change in the
frequency of stool
Onset
associated with
a change in the
form of stool
* Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
Diagnosis of IBS
A diagnosis of IBS requires identifying characteristic symptoms and excluding organic disease. Making an early, definitive, and clinically based diagnosis can be reassuring to
patients, especially those concerned about eliminating a serious cause for their symptoms, and can minimize the cost and
inconvenience of unnecessary testing.
Until recently, IBS was considered a “diagnosis of exclusion,” or a condition whose presence cannot be established
from examination or testing, with diagnosis requiring elimination of other possibilities.29,30 Clinicians may do well, instead,
to view IBS as a clinically based diagnosis rather than one
made as a last resort, after other disorders have been eliminated.
Attempting to exclude other disorders can result in unnecessary and expensive testing, such as functional brain imaging,
abdominal x-ray, and ultrasonography. Providers who believed
IBS was a diagnosis of exclusion ordered 1.6 more tests and
spent $364 more per patient on diagnostic workup than those
who did not,29 thus increasing the cost burden for the patient.
Clinicians can confidently diagnose IBS by using symptombased criteria and excluding alarm features suggestive of disorders other than IBS (ie, new onset of symptoms in patients older
than age 50, unexplained weight loss, GI bleeding, progressive
or unrelenting pain, nocturnal or large-volume diarrhea, and
a family history of colon cancer, inflammatory bowel disease
[IBD; see “A New Way to Diagnose? Making IBS a “Diagnosis
of Inclusion”], or celiac sprue).31 Although no single biological
marker can identify patients with IBS-C,29 a thorough history
and physical examination combined with the exclusion of medical conditions that are clinically similar to IBS can typically
enable clinicians to establish a diagnosis of IBS.30
Clinicians may occasionally employ diagnostic tools such
as routine blood tests, stool studies for infection, radiographic
imaging, or endoscopic procedures such as upper endoscopy,
sigmoidoscopy, and colonoscopy in selected patients30,32;
however, more extensive and repetitive investigations may
create uncertainty detrimental to the successful management
of patients with IBS because the positive predictive value of
such tests remains small.33 Unnecessary investigations could
prevent the diagnosis and treatment of a patient with IBS
because of misleading test results. Clinicians should consider
the age, symptom pattern, history, and alarm signs/symptoms
of the patient before ordering diagnostic testing.32 It should be
noted that the American College of Gastroenterology (ACG)
does not encourage the routine use of diagnostic tests in IBS
patients who do not also present with alarm features; however,
routine testing for celiac disease may be considered, especially
in individuals with frequent diarrhea.30 The ACG encourages
colorectal cancer screening for all patients, including IBS
Symptom-Based Criteria: Rome III Diagnostic Criteria
for Diagnosis
The symptom-based Rome III diagnostic criteria for IBS offer
clinicians the best tool for an accurate diagnosis. The Rome
III diagnostic criteria require the combination of recurrent
abdominal pain or discomfort for at least 3 days per month in
the last 3 months, with at least 2 of the following: symptoms
were improved with defecation, onset was associated with
a change in the frequency of stool, or onset was associated
with a change in the form (consistency) of the stool.1 These
symptoms must have started at least 6 months before diag-
Conquering IBS in Women: The Clinician’s Pursuit of Optimum Management Strategies
Table 2. ABCs for Diagnosis in Women5,37-39
Accurate, directed patient history
•Symptoms (nature, duration,
and characteristics)
•Gynecologic issues (fibroids, dysmenorrhea, ovulation, pregnancy, etc)
•Medications (laxatives, oral contraceptives, etc)
•Emotional distress
•History of abuse
physical
examination
•Abdominal examination
•Digital rectal examination
(include assessment for rectocele)
•Pelvic examination, when indicated
•Assessment of neurologic function
of diagnostic tests
•Rule out systemic disease or
obstruction based on factors listed above
•Colonoscopy (in patients with significant family history, in patients aged ≥50 years, or in the presence of alarm symptoms)
Brief, focused Careful selection and/or diarrhea.30,32 Clinicians should remember, however, that
there are noticeable differences in IBS symptoms based on
gender. Table 2 provides a helpful guide to diagnosing IBS in
women.5,37-39 A detailed patient history should include gynecologic issues and pregnancy, which have been shown to play a
role in IBS. In addition, clinicians should perform a brief and
focused physical examination and carefully select diagnostic
tests to rule out systemic disease or obstruction.
Female IBS patients often report abdominal distension
associated with bloating, constipation, nausea, alterations of
taste and smell, an unpleasant sensation on the tongue, muscle
stiffness in the morning, depression, anxiety, somatization,
greater food sensitivity, and medication side effects.4 Clinicians should bear in mind that other conditions sometimes
mimic IBS in women: chronic pelvic pain, endometriosis,
worsening of GI symptoms during menstruation, dyspareunia
(painful sexual intercourse), or other gynecologic-associated
symptoms can confound a diagnosis.1,32
Furthermore, the symptoms of a variety of GI conditions
resemble those of IBS. Such conditions include chronic constipation, IBD, microscopic colitis, infectious colitis, celiac
disease, colon cancer, small intestinal bacterial overgrowth,
functional dyspepsia, and gallstones.32,33,40 In addition to
gynecologic problems, non-GI conditions in the differential
diagnosis of IBS, such as musculoskeletal pain and renal
colic, should also be weighed.4 Gynecologic symptoms associated with IBS, chronic pelvic pain (defined as pelvic pain ≥6
months’ duration), and a wide range of reproductive disorders
such as dysmenorrhea, endometriosis, and pelvic congestion
affect approximately 15% of women.41,42
patients. For the average-risk patient, individual screening
should begin at age 50.34
A New Way to Diagnose? Making IBS a “Diagnosis of Inclusion”
An emerging school of thought among IBS researchers is to
make the disease a “diagnosis of inclusion,” in order to distinguish IBS from other bowel disorders such as IBD. IBD
is a chronic inflammatory disease of the GI tract that also
comprises ulcerative colitis and Crohn’s disease. The reported
prevalence of symptoms suggestive of IBS varies from 33%
in ulcerative colitis patients in remission to 57% in Crohn’s
disease patients in remission.35 Although IBD symptoms flare
and remit over weeks to months, IBS symptoms tend to fluctuate on a daily basis.36 It should be noted, however, that a sizable number of patients with IBD in remission display bowel
symptoms resembling IBS.35
Low and colleagues found that the Rome criteria alone did
not help discriminate IBD from IBS because 86.7% of IBD
patients also met the criteria for IBS36; however, in contrast to
the Rome criteria, varied stool form and frequency can readily
separate IBD from IBS, even in the absence of alarm symptoms. Devising criteria for a diagnosis of IBS based on stool
form and frequency in addition to applying the Rome criteria
might help establish IBS as a diagnosis of inclusion and also
arm clinicians with a more robust clinical tool.
Referral to a Gastroenterologist
Although most patients with IBS can be treated by their primary care provider, clinicians should refer patients to gastroenterologists when symptoms do not fit the ACG or Rome III
criteria, or when initial treatment fails.32 Referral is also warranted when patients display alarm features such as30,32:
• Hematochezia
• Weight loss >10 lb
• A family history of colon cancer or IBD
• Positive fecal occult blood test
• Recurring fever
• Anemia
• Severe diarrhea
• Acute onset of symptoms
• Onset of symptoms in elderly patients
Patient-Clinician Communication
Most IBS patients present to their primary care providers, who
are in the best position to know a patient’s history, personality,
and family.1 Patients presenting to specialists are more likely to
have severe symptoms, anxiety, panic, depression, or other complicating psychosocial disorders that require special treatment.
An effective clinician-patient relationship is the cornerstone of successful care for IBS, and good patient-clinician
Diagnostic Considerations in Women
Common IBS symptoms in most patients include abdominal
pain or cramping associated with a change in bowel habits,
bloating, flatulence, mucus in the stool, and constipation
communication has been shown to improve outcomes.33
Unfortunately, frustration often pervades the patient-clinician
relationship when proper care is delayed and patient anxiety
and treatment costs are increased (Figure 3).18
make connections between stress, diet, and (for women) menstrual cycle phase and symptoms. Patients should also be urged
to take an active role in treatment, including monitoring their
food intake. Although major exclusion diets are not recommended and have not been proven to reduce IBS symptoms,
specific foods may trigger symptoms.32 Clinicians should
evaluate patients for lactose intolerance; laxative effect of certain foods (caffeine, fructose, sorbitol, and/or herbal products);
gas/bloating caused by carbonated beverages; intake of certain
foods such as beans, cabbage, and broccoli; use of chewing
gum; and fat, carbohydrate, and fiber intake.
Figure 3. Patient-Clinician Cycle of Frustration18
Anxiety
Hypervigilance
Patient Experience
Urgent visits,
Requests tests
• Pain
• Disability
• Expects cure
Communicating With Female IBS Patients
Patient Cognitions
• Dissatisfaction
• Pessimism
• Maladaptive coping
• Lack of control
Most patients respond to physicians who are willing to listen
to their concerns, spend time with them, and show interest
in building a strong clinician-patient relationship.1 Taking a
multifaceted treatment approach can reduce health care utilization. Clinicians should have a professional, understanding
demeanor and encourage patients to ask questions. Furthermore, they should avoid overtesting and harmful treatments.
Dissatisfied patients may visit multiple clinicians, endure
dangerous or unnecessary investigations, take improper medications, and undergo unjustified surgeries.
Clinicians should note that female IBS patients typically
have individual concerns. Although some of the questions
listed in Table 3 could also pertain to men, the table includes
female-specific questions that clinicians should ask women
who present with symptoms suggesting IBS.1,4,26,43-45
The Bristol Stool Form Scale is a helpful tool that can facilitate patient-clinician communication (Figure 4).46 The scale’s
Physicians
•
•
“Organic” etiology
focus
“Drained” biased
attitudes
Referrals, tests, drugs, surgery,
iatrogenic harm, high costs
To break the cycle illustrated in Figure 3, clinicians should
strive to be nonjudgmental and should take a patient-centric
approach when conducting patient interviews, by educating
patients about their condition and involving them in treatment
decisions.33 Clinicians should explore stress-related
symptoms or comorbid psychological concerns that
Table 3. Key Questions to Ask Female Patients With IBS1,4,26,43-45
could exacerbate the severity of illness, impede
daily functioning, and impair health-related outcomes. In addition to calming the natural fears of
• Have you experienced significant, • Do you need to perform
continuous, or repeated episodes manual maneuvers to assist
their IBS patients, clinicians should investigate any
of any of the following?
with defecation?
unstated patient concerns or aggravating factors.1
•
Abdominal
pain
They should assess the level of daily functioning,
• Bloating
personality, recent life stress (eg, divorce, job loss,
• Nausea
or bereavement), and any psychological disturbance. Symptom type and severity and the nature
• What is the frequency of your • Is there a change in frequency
of associated psychosocial issues should define the
bowel movements?
or intensity of symptoms course of treatment. Symptom perception may be
during menstruation?
further altered by psychological factors. A patient’s
• Could you be pregnant?
• Are you taking oral reaction to these symptoms may be more significant
contraceptives?
than the symptoms themselves.
• Are you taking hormone • Have you ever exhibited any
Patients also have a role to play in breaking the
replacement therapy for menopause? eating disorder behavior?
cycle by acting as their own advocate. This includes
• Are you experiencing painful • Do you have any current
becoming educated about their condition as well as
sexual intercourse?
gynecologic problems taking a proactive role in treatment decisions.33 Since
(eg, endometriosis, fibroids)?
treatment of IBS is often focused on specific symptoms, patients should maintain a regular symptom
• Do you have a history of physical or diary or log. This also allows patients to note when
sexual abuse? (This history must be
elicited privately and with care)
and which symptoms occur and what appears to trigger an event. Keeping a diary can often help patients
Conquering IBS in Women: The Clinician’s Pursuit of Optimum Management Strategies
utility rests with its ability to enable patients to accurately
describe their BMs. The Bristol scale illustrates all stool types,
ranging from type 1 (separate hard lumps) to type 7 (watery
with no solid pieces). Clinicians can develop appropriate
diagnostic and therapeutic strategies when patients describe
their stool accurately. Clinicians may also have a better idea of
the psychological impact of the symptoms, based on how the
patient responds to open-ended questions about his/her stool.
functional obstruction or dyssynergic defecation. In addition,
perineal descent during straining can be assessed; when abnormal, this can also lead to a functional type of obstruction.
Treatment of IBS
Treatment of IBS includes both nonpharmacologic and pharmacologic therapies. Components of nonpharmacologic treatment of IBS include patient education, diet recommendations,
lifestyle modifications, and psychological intervention.
Figure 4. Bristol Stool Form Scale46
Behavioral therapies focus on reducing stress and stressrelated triggers of IBS symptoms, increasing
THE BRISTOL STOOL FORM SCALE
relaxation, and reducing negative self-talk. Examples of behavioral therapy include relaxation
Slow
Type 1
Separate hard lumps
therapy, biofeedback, hypnotherapy, cognitive
gut
therapy, and psychotherapy. Drossman and coltransit
Type 2
Sausage-like but lumpy
leagues found that women with IBS showed an
improvement in global satisfaction and quality of
Type 3
Sausage-like but with cracks life following cognitive behavioral therapy com
in the surface
pared with education alone.48
Reassurance and support is also crucial for the
IBS patient. Clinicians should emphasize that IBS
Type 4
Smooth and soft
is not a life-threatening disorder and should reassure patients that their symptoms are not imagiType 5
Soft blobs with clear-cut edges
nary.32 They should also inform their patients that
IBS symptoms have physiologic causes that are
poorly understood. Psychotherapy can also miniType
6
Fluffy
pieces
with
ragged
edges,
Rapid
mize patient anxiety.32,49
a
mushy
stool
gut
transit
Type 7
Watery, no solid pieces
Lifestyle Modifications
Implementing dietary and lifestyle changes in
patients with IBS may prove beneficial, but the
effectiveness of these treatments has not been fully validated
from an evidence-based perspective. Although lifestyle modifications alone are typically not effective for patients with IBS,
maintaining a healthy lifestyle can prevent other diseases and
should therefore be encouraged by clinicians.
Ensuring adequate hydration (1.5 to 2 L of fluid per day) is
a commonly recommended lifestyle modification and is especially beneficial in patients who are dehydrated.50 Furthermore,
patients may benefit from increasing their dietary fiber intake; it
is recommended that individuals consume at least 25 g per day.
It may be helpful to gradually increase the fiber dose instead
of starting with a high dose because fiber may cause bloating.
Other lifestyle modifications include initiating regular nonstrenuous physical exercise (such as walking or swimming) and
having patients schedule dedicated bathroom time.
Patients with IBS may also benefit from probiotics. Probiotics are thought to work by several mechanisms, including shifting from a pro-inflammatory to an anti-inflammatory cytokine
profile, decreasing the transport of bile acid to the colon, and
modulating intestinal motility.33 Bifidobacterium animalis may
reduce colonic transit time, and Lactobacillus casei may improve
constipation severity and stool consistency.51 A 2005 trial of probiotics comparing either Bifidobacterium infantis or Lactobacillus salivarius to placebo in 75 patients with IBS over a 12-week
Digital Rectal Examination
Performing a digital rectal examination (DRE) can identify
the presence of perianal lesions, offer an assessment of muscle
strength and function, and provide information about stool consistency or blood in the stool.38 The DRE may be the most important
component of the physical examination of an IBS patient.
When performing the DRE, clinicians should place the
patient in the left lateral recumbent position and visually
inspect the perianal region for abnormalities (eg, hemorrhoids,
fissures, or prolapse).38,43 IBS has been shown to be a prevalent
condition in patients with hemorrhoids.47 Clinicians should
evaluate the muscle strength of both the internal and external
anal sphincter and pelvic floor, and then assess the anal canal
with a sweep of the examining finger, checking for nodules,
irregularities, or tenderness. Finally, female patients should be
assessed for rectocele, a condition occurring when the wall of
the rectum bulges into the vagina.
During a DRE, it is important to instruct the patient to bear
down as if he/she is defecating.38,43 During this maneuver,
clinicians should feel the relaxation of the external sphincter;
if muscle function appears normal, pelvic floor dysfunction is
less likely, but if there is heightened contraction during defecation, the clinician, while bearing in mind that the patient may
be experiencing embarrassment or inhibition, should consider
treatment period showed a significant reduction Table 4. Current Pharmacologic Treatment Options for IBS30,32,33,54
in abdominal pain and discomfort, bloating, and
difficulty with BMs with B infantis, but not with
Treatment
Indication
Evidence
L salivarius.52
Recent Changes in Available Pharmacologic
Options
Tegaserod, a partial 5-HT4 agonist that had
been shown to be effective in relieving the
global symptoms of IBS-C, was voluntarily
withdrawn from the US market by its manufacturer in March 2007, then reintroduced
as a limited investigational new drug in July
2007.53 In April 2008, however, tegaserod was
once again voluntarily withdrawn from the US
market and is now only available for emergency situations, defined by the US Food and
Drug Administration (FDA) as immediately
life-threatening or serious enough to require
hospitalization.53 Although the manufacturer
of tegaserod will supply the drug for these
situations, requests must be approved, and
shipments of the drug must be authorized by
the FDA.
Current Pharmacologic Treatment Options
for IBS
Chloride channel activator (lubiprostone)
IBS-C in women
aged >18 years
More effective than placebo over
a 12-week treatment period
Bulking agents
(psyllium)
IBS
Not more effective than placebo
at relieving global IBS symptoms
Osmotic laxatives
(polyethylene glycol [PEG] 3350, lactulose)
IBS-C
More effective than placebo
at improving IBS symptoms
Antidiarrheals
(loperamide)
IBS-D
Not more effective than placebo
at relieving global IBS symptoms
Antispasmodics (dicyclomine, hyoscyamine)
IBS-M
Insufficient data to make a
recommendation about the efficacy in IBS
Tricyclic antidepressants (desipramine)
IBS-D
IBS-M
Not more effective than placebo
at relieving global IBS symptoms; improves abdominal pain in IBS patients
Serotonin reuptake inhibitors (SSRIs,
eg, citalopram)
IBS-C
More effective than placebo at
relieving abdominal pain and
improving overall well-being in some IBS patients
Antibiotics
(rifaximin)
IBS
More effective than placebo at
improving IBS symptoms
Pharmacologic therapy is best used in IBS
5-HT3 receptor IBS-D with
More effective than placebo at
patients with moderate to severe symptoms
antagonists restricted relieving symptoms
refractory to clinician counseling and dietary/
(alosetron)
availability
lifestyle modifications. Treatment has traditionally been aimed at the most bothersome IBS, irritable bowel syndrome; IBS-C, IBS with constipation; IBS-D, IBS with diarrhea; IBS-M, IBS with symptom because of the lack of effective treat- mixed bowel pattern.
ment for the overall improvement of multiple
symptoms; however, new therapies for IBS have recently been at all effective; 4=extremely effective). Although patients taking
introduced and shown to effectively treat multiple symptoms. lubiprostone in increasing doses noted greater treatment efficacy
Table 4 lists the current pharmacologic treatment options for than did those taking lesser doses, side effects were greater with
IBS.30,32,33,54
the larger doses. Patients taking all doses of lubiprostone scored
higher than did patients taking placebo.
Chloride Channel Activator: Lubiprostone
Lubiprostone should not be given to patients who have
In April 2008, the FDA approved lubiprostone for the treat- severe diarrhea or patients with bowel obstructions.54 Furment of IBS-C in women aged 18 years or older, making it the thermore, its safety and efficacy have not been established in
only FDA-approved medical treatment for IBS-C available in patients with renal or hepatic impairment, pregnant patients,
the United States. The approved dose is 8 µg BID, taken with or nursing mothers. The most common adverse events associfood and water.54 It is also important to differentiate appropriate ated with lubiprostone are nausea, diarrhea, and headache,57
lubiprostone doses for different diseases; the approved dose for although recent data suggest that nausea is decreased when
chronic idiopathic constipation (1 to 2 BMs/week) is 24 µg BID. lubiprostone is administered with food and water. LubiprosIn two 12-week, phase III, multicenter, double-blind, random- tone is classified as a pregnancy class C medication.
ized, placebo-controlled studies, patients receiving lubiprostone
were nearly twice as likely as those receiving placebo to achieve Bulking Agents
an overall response.55 Additionally, a dose-finding study of 193 Bulking agents include psyllium, methylcellulose, calcium
subjects by Johanson and colleagues in 2008 showed that 8-µg polycarbophil, corn fiber, and ispaghula husk.33 Initial manBID doses of lubiprostone provided optimal combined benefits agement of IBS has often included fiber supplementation;
of efficacy and limited adverse events.56 Patients self-rated their however, the ACG Functional Gastrointestinal Disorders Task
efficacy of treatment after 1 month on a scale of 0 to 4 (0=not Force assessed randomized, placebo-controlled treatment tri-
Conquering IBS in Women: The Clinician’s Pursuit of Optimum Management Strategies
als for IBS and reported that none of the trials evaluating bulking agents were of high quality.30
Bulking agents in therapeutic quantities can cause adverse
effects, such as bloating and abdominal pain and discomfort.33
Patients who wish to take bulking agents, particularly those
who have insufficient dietary fiber intake or who experience
bloating, should be reminded to initiate the recommended dose
gradually to minimize side effects. Psyllium is classified as a
pregnancy category B medication.57
an advantage over placebo.64,65 This class of drugs works best
in patients who have abdominal pain and diarrhea or IBSM.32 Clinicians are advised to warn their patients about early
side effects (ie, fatigue, dry mouth) that generally improve
over time.66
Selective Serotonin Reuptake Inhibitors
TCAs and selective serotonin reuptake inhibitors (SSRIs)
may work by addressing visceral hypersensitivity. As noted
above, one of the pathophysiologic mechanisms proposed
for IBS is visceral hypersensitivity.20 Altered communication between the brain and the gut might work to enhance
the sensation of pain; these medications may also modify
communication via the brain-gut axis. SSRIs have fewer
side effects than TCAs, making them more attractive to
IBS patients.16 Few trials have addressed their efficacy;
those doing so included few study subjects. SSRIs appear
to have a mild analgesic effect and may also reduce the
reporting of multiple bodily symptoms or somatization.
A study conducted by Tack and colleagues in 23 patients
showed an improvement in abdominal pain and bloating
with citalopram compared with placebo after 6 weeks of
treatment.67 Citalopram is classified as a pregnancy class C
medication.57
Osmotic Laxative: Polyethylene Glycol 3350
Polyethylene glycol (PEG) 3350 is an FDA-approved osmotic
laxative often used for short-term constipation,37 but it also has
applicability for moderate IBS-C. PEG is no longer available
by prescription; over-the-counter PEG 3350 is indicated for
occasional constipation for up to 7 days.58
PEG 3350 is a synthetic polyglycol that is not absorbed and
results in an increased osmotic load within the lumen of the
small intestine and colon, leading to luminal distension and
increased peristalsis.57 A 2006 study conducted by Khoshoo
and colleagues reported that PEG 3350 increased the mean
frequency of BMs from 2.07 to 5.04 per week and slightly
decreased the mean pain level in the 27 IBS-C patients.59
Common adverse events associated with PEG 3350 include
nausea, abdominal bloating, and cramping.58 Use of PEG 3350
might result in electrolyte disturbances. PEG 3350 is classified
as a pregnancy category C medication.
Antibiotics
Rifaximin has shown promise in improving IBS symptoms.
In a randomized, placebo-controlled trial of 124 patients
that encompassed 3 10-day phases (phase 1=baseline, phase
2=treatment of rifaximin 400 mg BID or placebo, phase
3=posttreatment), rifaximin improved abdominal bloating and
flatulence.68 Rifaximin provided better global symptom relief
than placebo when measured at the end of phase 2 (41.3% vs
22.9%, P=0.03), and improved symptoms were also measured
at the end of phase 3 (28.6% vs 11.5%, P=.02).68 These results
were confirmed in a double-blind, placebo-controlled, parallel-group study of 87 IBS patients published in 2006.69 At the
end of treatment, more patients in the rifaximin group reported
global improvement in their IBS symptoms (37.7% vs 23.4%)
(P <.05) and clinical response (37.2% vs 15.9%) (P <.05).69
However, more data proving rifaximin does not induce bacterial resistance are needed before the drug gains widespread
acceptance.62
Antidiarrheal Agents
In IBS-D patients, antidiarrheal agents such as loperamide
can be effective in decreasing BM frequency. Loperamide
limits peristalsis and fluid secretion, resulting in longer gastrointestinal transit time and increased absorption of fluids
and electrolytes from the gastrointestinal tract. Loperamide,
however, does not decrease the abdominal pain associated with
IBS-D.60 Common adverse reactions to loperamide include
cramps and nausea. Loperamide is classified as a pregnancy
class C medication.57
Antispasmodics
Antispasmodics are the most commonly prescribed medications for IBS.61 The antispasmodic agents available in the
United States are dicyclomine and hyoscyamine.62 In a review
of 11 randomized, placebo-controlled trials (N=1260) of antispasmodics, bulking agents, and antidepressants in IBS, antispasmodics were the only class of IBS treatment medications
that reduced abdominal pain and resulted in the improvement
of symptoms.63 There is no firm evidence, however, that these
agents are efficacious in the IBS population as a whole; 3 of
4 placebo-controlled trials suggested antispasmodics are no
more effective than placebo in improving IBS symptoms.62
Serotonin Type 3 Antagonists (5-HT3)
The 5-HT3 antagonist alosetron has been shown to improve
diarrhea in female IBS-D patients. A 2007 study by Krause
and colleagues showed improvement with all doses of alosetron at 12 weeks.70 However, concerns about ischemic colitis
and severe constipation57 have prompted withdrawal of alosetron in many countries. In the United States, alosetron is available on a restricted basis only for women with severe IBS-D
who have chronic IBS symptoms and have not responded to
conventional therapy.71 Alosetron is listed as a pregnancy class
B medication.57
Tricyclic Antidepressants
A meta-analysis and a double-blind, randomized, controlled
trial demonstrated that tricyclic antidepressants (TCAs) offer
10
Table 5. Emerging Treatment Options for IBS72-74
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To take the posttest and receive CME/CPE/CE credit, please
visit the following Web site: http://totalmeded.com/ibsmonograph
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