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A Gap in Our Understanding: Chronic Constipation and Its Comorbid Conditions

  • Nicholas J. Talley
    Correspondence
    Address requests for reprints to: Nicholas J. Talley, MD, PhD, FACP, FRACP, FRCP, Chair, Department of Internal Medicine, Mayo Clinic Jacksonville, Professor of Medicine and Epidemiology, Mayo Clinic College of Medicine, Consultant, Division of Gastroenterology & Hepatology, 4500 San Pablo Road, Jacksonville, Florida 32224. fax: (904) 953-7366
    Affiliations
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic Florida, Jacksonville, Florida
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  • Karen L. Lasch
    Affiliations
    Takeda Pharmaceuticals North America, Inc. Medical & Scientific Affairs, Deerfield, Illinois
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  • Charles L. Baum
    Affiliations
    Takeda Pharmaceuticals North America, Inc. Medical & Scientific Affairs, Deerfield, Illinois
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Published:October 02, 2008DOI:https://doi.org/10.1016/j.cgh.2008.07.005
      Constipation is one of the most common digestive disorders in the United States; however, the association of this condition with related comorbidities, both gastrointestinal and extraintestinal, is poorly documented. Here, we have reviewed the association of constipation with specific comorbidities. The data suggest that there are considerable clinical consequences associated with constipation. Ultimately, realization of the disease risks associated with chronic constipation may provide the impetus needed to direct new research, and shift attention on the part of patients and practitioners to methods for preventing significant and potentially costly comorbid medical problems.

      Abbreviations used in this paper:

      US (United States), UTI (urinary tract infection)
      Constipation is one of the most common digestive disorders in the United States, with most prevalence estimates ranging from 12% to 19%.
      • Higgins P.D.
      • Johanson J.F.
      Epidemiology of constipation in North America: a systematic review.
      • Locke III, G.R.
      • Pemberton J.H.
      • Phillips S.F.
      AGA technical review on constipation American Gastroenterological Association.
      Over the past 15 years, the clinical recognition of constipation has been improved by an ongoing evolution in symptom-based diagnostic criteria referred to as the Rome classification system (currently, Rome III).
      • Longstreth G.F.
      • Thompson W.G.
      • Chey W.D.
      • et al.
      Functional bowel disorders.
      The Rome criteria have facilitated a standardized differentiation between patients with occasional or intermittent constipation from those with chronic functional constipation, who likely carry the largest health care cost and medical burden. The economic burden of constipation has been underappreciated until recent studies showed that chronically constipated patients may have costs that are at least 50% higher than nonconstipated controls.
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare utilization and costs associated with constipation and co-occurring irritable bowel syndrome and constipation compared to matched controls in a large managed care population.
      In the United States, constipation-related health care costs averaged about $235 million in 2001
      • Martin B.C.
      • Barghout V.
      The annual cost of constipation in the U.S. ambulatory and inpatient care settings.
      ; and the mean annual cost for treatment of chronic constipation has been estimated to be $7522 per patient.
      • Nyrop K.A.
      • Palsson O.S.
      • Levy R.L.
      • et al.
      Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain.
      The high prevalence and associated medical costs suggest that there are significant clinical sequelae of chronic constipation, but a paucity of data on constipation and its comorbidities exists in the literature. Several recent retrospective studies of large databases have documented an increase in medical conditions, particularly gastrointestinal complications, associated with constipation. Specifically, in surveys of the California Medicaid (Medical) and large US health plan populations, Singh et al
      • Singh G.
      • Kahler K.
      • Bharathi V.
      • et al.
      Constipation in adults: complications and comorbidities.
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      and Mitra et al
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      showed an emerging pattern of comorbid conditions (Table 1).
      Table 1Gastrointestinal Comorbidities of Constipation
      Singh et al, 2007
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      OR (95% CI)
      Mitra et al, 2007
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      OR (P value)
      Singh et al, 2005
      • Singh G.
      • Kahler K.
      • Bharathi V.
      • et al.
      Constipation in adults: complications and comorbidities.
      RR (95% CI)
      MethodsReview of MediCal databaseRetrospective analysis of insurance claims from US health planReview of MediCal database
      Subjects147,595 with constipation (US)
      1 year after vs 1 year before constipation.
      48,585 with constipation; 97,170 controls (US)105,130 with constipation; 1,266,547 controls (US)
      Constipation criteriaICD-9 code 564.0xICD-9 code 564.0xICD-9 code 564.0x
      Comorbidity, n (range)
       Hemorrhoids2.9 (2.8–3.0)4.19 (< .01)4.10 (4.01–4.18)
       Anal fissures3.1 (2.7–3.5)5.04 (< .01)4.80 (4.46–5.16)
       Stercoral ulcerNA4.76 (< .01)3.23 (2.91–3.58)
       Fecal impaction5.6 (5.1–6.1)6.58 (< .01)5.95 (5.68–6.24)
       Fecal incontinence1.7 (1.5–2.0)NANA
       Obstruction3.4 (3.2–3.7)4.10 (.01)3.38 (3.3–3.5)
       Volvulus3.3 (2.6–4.2)10.34 (.01)3.67 (3.25–4.15)
       Diverticular disease2.8 (2.7–2.9)NANA
       Megacolon5.0 (3.8–6.8)NANA
       Rectal prolapse2.3 (1.9–2.9)NANA
       Colon cancer2.2 (2.0–2.4)NANA
      OR, odds ratio; CI, confidence interval; RR, relative risk; ICD-9, International Classification of Diseases, 9th revision; NA, not applicable.
      low asterisk 1 year after vs 1 year before constipation.

      Pathophysiologic Mechanisms

      Chronic constipation, as defined by the Rome III criteria, specifies a minimum 6-month history of symptoms to establish chronicity. The hallmark symptoms include straining, a sense of incomplete evacuation, bowel movement infrequency, and hard stool consistency.
      • Longstreth G.F.
      • Thompson W.G.
      • Chey W.D.
      • et al.
      Functional bowel disorders.
      Of these constipation-defining symptoms, hard stool, straining, and the associated increase in intra-abdominal pressure may be etiologically important in clinical sequelae, such as hemorrhoids, anal fissures, and possibly rectal prolapse. Although there may be a similar etiology for diverticular disease, this has been difficult to document. Thus, although abnormal stool consistency and straining are common in clinical practice, the events leading to changes in gastrointestinal symptomatology have not been firmly established.
      Conceptually, constipation with retention of hardened stool can initiate development of stercoral ulcer and fecal impaction with overflow fecal incontinence in both adults and children. Furthermore, infrequent bowel movements and an increase in colonic capacitance and size can lead to megacolon, volvulus, and compression of the surrounding anatomy. Pudendal neuropathy resulting from nerve compression and exaggerated perineal descent seen with excessive defecatory straining
      • Henry M.M.
      • Parks A.G.
      • Swash M.
      The pelvic floor musculature in the descending perineum syndrome.
      could mechanistically explain a spectrum of pelvic floor disorders, including prolapse and fecal incontinence. Although rectocele is not an uncommon finding in patients with evacuatory disorders, its pathogenesis is still controversial.
      • Locke III, G.R.
      • Pemberton J.H.
      • Phillips S.F.
      AGA technical review on constipation American Gastroenterological Association.
      Thus, the pathophysiologic link between constipation and comorbid diseases remains poorly understood. Awareness of at-risk diseases is important as part of clinical surveillance especially because the management of constipation, at least in certain comorbidities, may improve outcome.
      • Alonso-Coello P.
      • Mills E.
      • Heels-Ansdell D.
      • et al.
      Fiber for the treatment of hemorrhoids complications: a systematic review and meta-analysis.
      • Alonso-Coello P.
      • Guyatt G.
      • Heels-Ansdell D.
      • et al.
      Laxatives for the treatment of hemorrhoids.
      • Mattana C.
      • Maria G.
      • Pescatori M.
      Rubber band ligation of hemorrhoids and rectal mucosal prolapse in constipated patients.
      • Jensen S.L.
      Diet and other risk factors for fissure-in-ano Prospective case control study.
      • Chassagne P.
      • Jego A.
      • Gloc P.
      • et al.
      Does treatment of constipation improve faecal incontinence in institutionalized elderly patients?.
      • Tobin G.W.
      • Brocklehurst J.C.
      Faecal incontinence in residential homes for the elderly: prevalence, aetiology and management.
      • Romanczuk W.
      • Korczawski R.
      Chronic constipation: a cause of recurrent urinary tract infections.
      • Neumann P.Z.
      • DeDomenico I.J.
      • Nogrady M.B.
      Constipation and urinary tract infection.
      • Anagnostopoulos D.
      • Mavromihalis J.
      • Markantonatos A.
      • et al.
      Constipation: a cause of enuresis.
      • O'Regan S.
      • Yazbeck S.
      • Schick E.
      Constipation, bladder instability, urinary tract infection syndrome.
      • O'Regan S.
      • Yazbeck S.
      • Hamberger B.
      • et al.
      Constipation a commonly unrecognized cause of enuresis.
      • Loening-Baucke V.
      Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood.
      • Erickson B.A.
      • Austin J.C.
      • Cooper C.S.
      • et al.
      Polyethylene glycol 3350 for constipation in children with dysfunctional elimination.
      • Charach G.
      • Greenstein A.
      • Rabinovich P.
      • et al.
      Alleviating constipation in the elderly improves lower urinary tract symptoms.
      Therefore, the aim of this article is to comprehensively review the recent literature, to explore in greater detail the association between constipation and its potential clinical complications, and to initiate an assessment of causality.

      Methods

      In Medline, a master search set comprised of the subject headings constipation and chronic constipation between the years 1980 and 2007 was created. Subject headings were selected and/or text queries were created for each of the following clinical concepts: hemorrhoids, anal fissures, fissure in ano, anal ulcer, rectal prolapse, stercoral ulcers, rectal ulcers, intestinal volvulus, fecal impaction, obstipation, obstruction, colonic pseudo-obstruction, gastric outlet obstruction, intestinal pseudo-obstruction, intestinal obstruction, bowel perforation, diverticulosis, diverticulitis, appendicitis, microscopic colitis, collagenous colitis, colorectal cancer, colorectal neoplasms, polyps, colonic polyps, intestinal polyps, familial adenomatous polyposis, rectal cancer, rectal neoplasms, depression, anxiety, anxiety disorders, irritable bowel syndrome, abdominal pain, migraine, fibromyalgia, obesity, morbid obesity, fecal incontinence, megacolon, chronic fatigue syndrome, vasovagal syncope, neuropathy, peripheral nervous system disease, pudendal nerve damage, pudendal nerve, urologic disease, urinary tract symptoms/infections, urinary incontinence, functional dyspepsia, and functional gastrointestinal disorders. Each clinical concept then was combined with the constipation set. The resulting citations and abstracts were reviewed in detail to select articles whose content may be suitable for discussing scientific evidence supporting or refuting an association between the earlier-described potential comorbidities and constipation. Articles cross-referenced in the citations and pertinent to the clinical concepts researched also were included.

      Results

      Relatively few publications were found in the literature dealing with the association of constipation and various search terms, supporting our initial impression that this area is largely unexplored. Given the limited data, we have confined our review to more commonly discussed anorectal, colonic, and urologic disorders. In the following discussion, each comorbidity is evaluated individually in the context of the currently proposed pathophysiology, specific to the disorder.

       Anorectal

       Hemorrhoids

      Both retrospective and prospective case-control studies have shown a significant association between constipation and hemorrhoids
      • Singh G.
      • Kahler K.
      • Bharathi V.
      • et al.
      Constipation in adults: complications and comorbidities.
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      • Delco F.
      • Sonnenberg A.
      Associations between hemorrhoids and other diagnoses.
      • Pigot F.
      • Siproudhis L.
      • Allaert F.A.
      Risk factors associated with hemorrhoidal symptoms in specialized consultation.
      (Table 1, Table 2), or an increase in the prevalence of hemorrhoids with a diagnosis of constipation
      • Brook R.A.
      • Talley N.J.
      • Kleinman N.L.
      • et al.
      Functional gastrointestinal disorder comorbidities: comparisons of prevalence and costs in the 6 months before and after diagnoses of constipation (C) and irritable bowel syndrome and constipation (IBS+C).
      (Table 2). Additional studies further documented an association between hemorrhoids and constipation symptoms such as straining, and related disorders such as fecal impaction.
      • Dehn T.C.
      • Kettlewell M.G.
      Haemorrhoids and defaecatory habits.
      • Read N.W.
      • Abouzekry L.
      • Read M.G.
      • et al.
      Anorectal function in elderly patients with fecal impaction.
      In contrast, 2 case-control studies showed no significant association between constipation and hemorrhoids
      • Johanson J.F.
      • Sonnenberg A.
      Constipation is not a risk factor for hemorrhoids: a case-control study of potential etiological agents.
      • Gibbons C.P.
      • Bannister J.J.
      • Read N.W.
      Role of constipation and anal hypertonia in the pathogenesis of haemorrhoids.
      (Table 2). It is notable that despite popular belief, Johanson and Sonnenberg
      • Johanson J.F.
      • Sonnenberg A.
      Constipation is not a risk factor for hemorrhoids: a case-control study of potential etiological agents.
      also found no association between hemorrhoids and increased age, cirrhosis, and varicose veins. Johanson and Sonnenberg
      • Johanson J.F.
      • Sonnenberg A.
      The prevalence of hemorrhoids and chronic constipation An epidemiologic study.
      found differences in the epidemiology (ie, dissimilar prevalence distributions by age, sex, and race) of constipation and hemorrhoids when evaluating 4 large, population-based data files in the United States, England, and Wales. Although these studies when taken together suggest that hemorrhoids may occur with equal frequency in patients with and without constipation, they do not necessarily rule out a causal relationship between a manifestation of constipation such as straining and hemorrhoids.
      Table 2Studies of Constipation and Hemorrhoids
      StudyMethodsSubjectsFindingsConstipation criteria
      Brook et al,
      • Brook R.A.
      • Talley N.J.
      • Kleinman N.L.
      • et al.
      Functional gastrointestinal disorder comorbidities: comparisons of prevalence and costs in the 6 months before and after diagnoses of constipation (C) and irritable bowel syndrome and constipation (IBS+C).
      2007
      Retrospective analysis of HCMS Research Reference Database1545 with constipation, 55,620 controls (US)8.4% increase in prevalence in the 6 months after versus before a diagnosis of constipation (P < .01)ICD-9 codes 564.0, 564.00, 564.01, 564.09
      Alonso-Coello et al,
      • Alonso-Coello P.
      • Mills E.
      • Heels-Ansdell D.
      • et al.
      Fiber for the treatment of hemorrhoids complications: a systematic review and meta-analysis.
      2006
      Systematic review of 7 trials378 patients randomized to fiber or nonfiber control for symptomatic hemorrhoidsRisk of not improving/persisting symptoms significantly decreased by 47% (RR, 0.53; 95% CI, 0.38–0.73) and risk of bleeding by 50% (RR, 0.50; 95% CI, 0.28–0.89) with fiber treatmentConstipation not measured
      Pigot et al,
      • Pigot F.
      • Siproudhis L.
      • Allaert F.A.
      Risk factors associated with hemorrhoidal symptoms in specialized consultation.
      2005
      Prospective, multicenter, case-control1033 with hemorrhoids, 1028 controls (France)Recent, acute episodes of constipation during the 15 days preceding consultation was a risk factor for hemorrhoidal crisis (OR, 3.93; 95% CI, 3.09–5.00)Patient report
      Delco and Sonnenberg,
      • Delco F.
      • Sonnenberg A.
      Associations between hemorrhoids and other diagnoses.
      1998
      Retrospective review of VA patient treatment file96,314 with hemorrhoids, 96,314 controls (US)Hemorrhoids significantly associated with constipation as a comorbid diagnosis (OR, 1.54; 95% CI, 1.48–1.61; P < .01)ICD-9 code in medical history
      Johanson and Sonnenberg,
      • Johanson J.F.
      • Sonnenberg A.
      Constipation is not a risk factor for hemorrhoids: a case-control study of potential etiological agents.
      1994
      Prospective survey in consecutive patients undergoing proctoscopy168 with hemorrhoids, 157 controls (US)Constipation not associated with hemorrhoids; ORs of 0.1, 1.5, 0.9 (95% CIs, 0.02–1.3, 0.5–4.1, 0.5–1.8) for infrequent stools, hard stools, and straining, respectively; increased age, cirrhosis, and varicose veins were not found to be associated with hemorrhoids eitherCriteria: infrequent stools (≤2/wk), hard stools, or straining
      Mattana et al,
      • Mattana C.
      • Maria G.
      • Pescatori M.
      Rubber band ligation of hemorrhoids and rectal mucosal prolapse in constipated patients.
      1989
      Prospective study of patients with hemorrhoids having rubber band ligation160 consecutive patients (Italy)Significantly higher hemorrhoid recurrence rate (85%) in patients with constipation versus those without (9%; P < .01)Less than 3 BMs per week or troublesome defecation
      Gibbons et al,
      • Gibbons C.P.
      • Bannister J.J.
      • Read N.W.
      Role of constipation and anal hypertonia in the pathogenesis of haemorrhoids.
      1988
      Prospective study of bowel habit, anal pressure profiles, and anal compliance23 prolapsing hemorrhoids, 12 severe constipation, 25 controls (United Kingdom)No significant difference in frequency, consistency, or ease of defecation between patients with hemorrhoids and normal subjects; hemorrhoid subjects did not report a definite history of constipation or regular strainingCriteria not defined
      HCMS, Human Capital Management Services; ICD-9, International Classification of Diseases, 9th revision; RR, relative risk; CI, confidence interval; OR, odds ratio; VA, Veterans Affairs; BM, bowel movement.
      It is possible that constipation may represent some adaptive response that lessens the risk of anorectal complications; however, the prevailing belief suggests that chronic straining and passage of hard stools result in degeneration of the supportive tissue in the anal canal, as well as a distal displacement of anal cushions, eventually leading to the development of hemorrhoids.
      • Thomson W.H.
      The nature of haemorrhoids.
      Further insight into the possible cause-and-effect relationship between constipation and hemorrhoids comes from intervention studies. Dietary modifications and administration of agents that minimize constipation have been associated with the prevention of recurrent, symptomatic hemorrhoids.
      • Alonso-Coello P.
      • Mills E.
      • Heels-Ansdell D.
      • et al.
      Fiber for the treatment of hemorrhoids complications: a systematic review and meta-analysis.
      • Alonso-Coello P.
      • Guyatt G.
      • Heels-Ansdell D.
      • et al.
      Laxatives for the treatment of hemorrhoids.
      • Mattana C.
      • Maria G.
      • Pescatori M.
      Rubber band ligation of hemorrhoids and rectal mucosal prolapse in constipated patients.

       Anal fissures

      Constipation is reported in more than 50% of patients with anal fissures, with about 25% of cases reporting the onset of constipation before fissure development.
      • Lubowski D.Z.
      Anal fissures.
      Pregnancy-associated constipation has been identified as a risk factor for anal fissure
      • Corby H.
      • Donnelly V.S.
      • O'Herlihy C.
      • et al.
      Anal canal pressures are low in women with postpartum anal fissure.
      • Abramowitz L.
      • Sobhani I.
      • Benifla J.L.
      • et al.
      Anal fissure and thrombosed external hemorrhoids before and after delivery.
      (Table 3). Similarly, in a pediatric population with constipation, as many as 1 in 4 patients may develop anal fissures.
      • Agnarsson U.
      • Warde C.
      • McCarthy G.
      • et al.
      Perianal appearances associated with constipation.
      A number of retrospective analyses generally support these findings
      • Singh G.
      • Kahler K.
      • Bharathi V.
      • et al.
      Constipation in adults: complications and comorbidities.
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      • Brook R.A.
      • Talley N.J.
      • Kleinman N.L.
      • et al.
      Functional gastrointestinal disorder comorbidities: comparisons of prevalence and costs in the 6 months before and after diagnoses of constipation (C) and irritable bowel syndrome and constipation (IBS+C).
      (Table 1, Table 3).
      Table 3Studies of Constipation and Anal Fissures
      StudyMethodsSubjectsFindingsConstipation criteria
      Brook et al,
      • Brook R.A.
      • Talley N.J.
      • Kleinman N.L.
      • et al.
      Functional gastrointestinal disorder comorbidities: comparisons of prevalence and costs in the 6 months before and after diagnoses of constipation (C) and irritable bowel syndrome and constipation (IBS+C).
      2007
      Retrospective analysis of HCMS Research Reference Database1545 with constipation, 55,620 controls (US)0.7% increase in prevalence in the 6 months after versus before a diagnosis of constipation (P < .01)ICD-9 codes 564.0, 564.00, 564.01, 564.09
      Abramowitz et al,
      • Abramowitz L.
      • Sobhani I.
      • Benifla J.L.
      • et al.
      Anal fissure and thrombosed external hemorrhoids before and after delivery.
      2002
      A consecutive study with proctologic examination in consecutive patients165 pregnant females (France)21 of 25 (84%) patients with anal fissure had dyschezia, compared with 22 of 107 (20.6%) patients with normal anal examinations (P < .01)Dyschezia defined as difficulty in completing rectal evacuation
      Corby et al,
      • Corby H.
      • Donnelly V.S.
      • O'Herlihy C.
      • et al.
      Anal canal pressures are low in women with postpartum anal fissure.
      1997
      Prospective study of incidence and etiology of anal fissure313 primigravid women (Ireland)Postnatal constipation was the only postpartum variable significantly more common in anal fissure patients (62%), compared with patients without anal fissure (29%); (χ2 = 10.6, 1 df, P < .01)Criteria not defined
      HCMS, Human Capital Management Services; df, degrees of freedom.
      Although little is known about the pathogenesis of the disorder, it has been proposed that anal fissures are initiated by direct trauma to the anal canal from hard stool.
      • Crapp A.R.
      • Alexander-Williams J.
      Fissure-in-ano and anal stenosis Part I: conservative management.
      Prolonged straining and forceful passage of hard stools may result in mucosal damage, with consequent rectal bleeding and painful defecation.
      • Corazziari E.
      • Staiano A.
      • Miele E.
      • et al.
      Bowel frequency and defecatory patterns in children: a prospective nationwide survey.
      Abramowitz et al
      • Abramowitz L.
      • Sobhani I.
      • Benifla J.L.
      • et al.
      Anal fissure and thrombosed external hemorrhoids before and after delivery.
      suggested that there also may be a regional ischemic component, resulting perhaps from discoordinate sphincter function. Regardless of the origin, once a fissure has formed, passage of hard stools tends to perpetuate the problem.
      • Crapp A.R.
      • Alexander-Williams J.
      Fissure-in-ano and anal stenosis Part I: conservative management.
      • Minguez M.
      • Herreros B.
      • Benages A.
      Chronic anal fissure.
      The management of anal fissures centers around treatment strategies directed at softening stool consistency and increasing stool volume, thereby physiologically dilating the anal sphincter and reducing mucosal trauma. Jensen,
      • Jensen S.L.
      Diet and other risk factors for fissure-in-ano Prospective case control study.
      in a prospective, case-control study, showed that dietary intake of raw fruits, vegetables, and whole-grain breads decreased the risk for developing anal fissures.

       Rectal prolapse

      Studies of patients with rectal prolapse have suggested an association with constipation
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      • Jacobs L.K.
      • Lin Y.J.
      • Orkin B.A.
      The best operation for rectal prolapse.
      • Hiltunen K.M.
      • Matikainen M.
      • Auvinen O.
      • et al.
      Clinical and manometric evaluation of anal sphincter function in patients with rectal prolapse.
      • Cirocco W.C.
      • Brown A.C.
      Anterior resection for the treatment of rectal prolapse: a 20-year experience.
      • Keighley M.R.
      • Shouler P.J.
      Abnormalities of colonic function in patients with rectal prolapse and faecal incontinence.
      • Mann C.V.
      • Hoffman C.
      Complete rectal prolapse: the anatomical and functional results of treatment by an extended abdominal rectopexy.
      • Tjandra J.J.
      • Fazio V.W.
      • Church J.M.
      • et al.
      Ripstein procedure is an effective treatment for rectal prolapse without constipation.
      (Table 1), with concomitant or preceding constipation in as many as 71% of adults
      • Tjandra J.J.
      • Fazio V.W.
      • Church J.M.
      • et al.
      Ripstein procedure is an effective treatment for rectal prolapse without constipation.
      • Peters III, W.A.
      • Smith M.R.
      • Drescher C.W.
      Rectal prolapse in women with other defects of pelvic floor support.
      and 27% of children.
      • Malyshev Y.I.
      • Gulin V.A.
      Our experience with the treatment of rectal prolapse in infants and children.
      • Zempsky W.T.
      • Rosenstein B.J.
      The cause of rectal prolapse in children.
      Anatomically, full-thickness rectal prolapse results from herniation of the rectum through a deficient pelvic floor.
      • Jacobs L.K.
      • Lin Y.J.
      • Orkin B.A.
      The best operation for rectal prolapse.
      Chronic straining with constipation is recognized as an etiologic factor in the development of rectal prolapse.
      • Peters III, W.A.
      • Smith M.R.
      • Drescher C.W.
      Rectal prolapse in women with other defects of pelvic floor support.
      Data from Keighley and Shouler,
      • Keighley M.R.
      • Shouler P.J.
      Abnormalities of colonic function in patients with rectal prolapse and faecal incontinence.
      combined with previous studies documenting delayed colonic transit times and a history of constipation in patients with rectal prolapse, suggest that a motility disorder may precipitate, or at least exacerbate, rectal prolapse.
      • White C.M.
      • Findlay J.M.
      • Price J.J.
      The occult rectal prolapse syndrome.
      • Moschcowitz A.V.
      The pathogenesis and anatomy and care of prolapse of the rectum.
      Although it appears that the majority of patients with rectal prolapse have concurrent constipation, other variables such as pelvic floor incoordination may predispose or contribute to this problem.
      • Peters III, W.A.
      • Smith M.R.
      • Drescher C.W.
      Rectal prolapse in women with other defects of pelvic floor support.

       Stercoral ulceration

      Stercoral ulceration is a form of pressure necrosis of the wall of the colon or rectum that results from a direct mass effect of retained feces. Lesions may vary in depth, ranging from mucosal ulceration to transmural perforation.
      • Maull K.I.
      • Kinning W.K.
      • Kay S.
      Stercoral ulceration.
      • deJong J.L.
      • Cohle S.D.
      • Busse F.
      Fatal stercoral ulcer perforation: case report.
      Stercoral ulceration generally is believed to be an uncommon condition; however, one of the largest, single-institution studies on stercoral perforation of the colon suggested that the incidence is underestimated, mainly because stercoral perforations are misdiagnosed as spontaneous, idiopathic, or secondary perforations.
      • Maurer C.A.
      • Renzulli P.
      • Mazzucchelli L.
      • et al.
      Use of accurate diagnostic criteria may increase incidence of stercoral perforation of the colon.
      The overall prognosis for stercoral ulceration is poor, with a mortality rate exceeding 50%, owing to a high risk of perforation and hemorrhage.
      • Maull K.I.
      • Kinning W.K.
      • Kay S.
      Stercoral ulceration.
      • Gekas P.
      • Schuster M.M.
      Stercoral perforation of the colon: case report and review of the literature.
      The role of hard feces in this condition, if any, is unclear. Unfortunately, there has been little work performed to determine the precedent role of constipation other than scattered case reports
      • Huang W.S.
      • Wang C.S.
      • Hsieh C.C.
      • et al.
      Management of patients with stercoral perforation of the sigmoid colon: report of five cases.
      • Avinoah E.
      • Ovnat A.
      • Peiser J.
      • et al.
      Sigmoid perforation in patients with chronic constipation.
      • Serpell J.W.
      • Nicholls R.J.
      Stercoral perforation of the colon.
      and insurance claims data analyses, which indicate a statistically significant increase in risk of stercoral ulcers in patients with a diagnosis of constipation
      • Singh G.
      • Kahler K.
      • Bharathi V.
      • et al.
      Constipation in adults: complications and comorbidities.
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      (Table 1).

       Fecal impaction

      Constipation and fecal impaction increase with age and are common in the elderly, institutionalized population.
      • Read N.W.
      • Celik A.F.
      • Katsinelos P.
      Constipation and incontinence in the elderly.
      Studies designed to determine the etiology and risk factors for fecal impaction are limited, although data from retrospective studies consistently have shown an increased risk in individuals diagnosed with constipation
      • Singh G.
      • Kahler K.
      • Bharathi V.
      • et al.
      Constipation in adults: complications and comorbidities.
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      (Table 1). The etiologic factors that lead to constipation in the elderly, such as loss of colonic motor function, anorectal sensory loss, debility, and fluid disturbances, also likely predispose to impaction.
      • Alessi C.A.
      • Henderson C.T.
      Constipation and fecal impaction in the long-term care patient.
      A rectum chronically loaded with feces can result in neuropathic impairment of rectal function,
      • Read N.W.
      • Abouzekry L.
      • Read M.G.
      • et al.
      Anorectal function in elderly patients with fecal impaction.
      predisposing to subsequent impaction, and, hence, a vicious cycle. Recognition of this process is critical to the management of elderly patients to prevent fecal impaction.

       Fecal incontinence

      Constipation and fecal incontinence frequently coexist, and can be debilitating in elderly patients.
      • Romero Y.
      • Evans J.M.
      • Fleming K.C.
      • et al.
      Constipation and fecal incontinence in the elderly population.
      Studies of nursing home residents reveal that fecal incontinence is the second most common cause for nursing home admissions.
      • Johanson J.F.
      • Lafferty J.
      Epidemiology of fecal incontinence: the silent affliction.
      Because of the embarrassing nature of this disorder, it is estimated that only one third of individuals with fecal incontinence have ever discussed the problem with a physician.
      • Johanson J.F.
      • Lafferty J.
      Epidemiology of fecal incontinence: the silent affliction.
      Both retrospective and prospective studies have indicated a positive association between constipation and fecal incontinence
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      • Nelson R.
      • Furner S.
      • Jesudason V.
      Fecal incontinence in Wisconsin nursing homes: prevalence and associations.
      • Ho Y.H.
      • Muller R.
      • Veitch C.
      • et al.
      Faecal incontinence: an unrecognised epidemic in rural North Queensland? Results of a hospital-based outpatient study.
      (Table 1, Table 4). However, some studies have indicated that constipation is not a risk factor for fecal incontinence
      • Johanson J.F.
      • Irizarry F.
      • Doughty A.
      Risk factors for fecal incontinence in a nursing home population.
      • Bharucha A.E.
      • Zinsmeister A.R.
      • Locke G.R.
      • et al.
      Risk factors for fecal incontinence: a population-based study in women.
      (Table 4).
      Table 4Studies of Constipation and Fecal Incontinence
      StudyMethodsSubjectsFindingsConstipation criteria
      Bharucha et al,
      • Bharucha A.E.
      • Zinsmeister A.R.
      • Locke G.R.
      • et al.
      Risk factors for fecal incontinence: a population-based study in women.
      2006
      Survey of age-stratified random sample in Olmstead County507 women with FI (US)Constipation was not a significant risk factor for FI (OR, 1.1; 95% CI, 0.8–1.5)Rome II criteria via FICA questionnaire
      Ho et al,
      • Ho Y.H.
      • Muller R.
      • Veitch C.
      • et al.
      Faecal incontinence: an unrecognised epidemic in rural North Queensland? Results of a hospital-based outpatient study.
      2005
      Prospective cross-sectional study435 consecutive patients (Australia)CC significantly associated with FI (P < .01); CART analysis identified patients with CC and UI as an extreme risk group for FI (45% prevalence)Patient report via questionnaire
      Nelson et al,
      • Nelson R.
      • Furner S.
      • Jesudason V.
      Fecal incontinence in Wisconsin nursing homes: prevalence and associations.
      1998
      2-year cross-sectional survey of HCFA's MDS submitted by a state's skilled nursing facilities18,224 nursing home residents; 16,331 with FI (US)CC was a significant risk factor for FI (ORs, 1.3–1.4; 95% CIs, 1.2–1.4 and 1.3–1.6)Listed in MDS as diagnosis or health condition
      Johanson et al,
      • Johanson J.F.
      • Irizarry F.
      • Doughty A.
      Risk factors for fecal incontinence in a nursing home population.
      1997
      Questionnaire388 nursing home residents (US)No significant association between CC and FI (OR, 1.1; 99% CI, 0.7–1.7)Subjective complaint
      FI, fecal incontinence; OR, odds ratio; CI, confidence interval; FICA, Fecal Incontinence and Constipation Assessment; CART, classification and regression trees; CC, chronic constipation; UI, urinary incontinence; HCFA, Health Care Finance Administration; MDS, minimum data set.
      The mechanism by which constipation predisposes to incontinence has been characterized as an overflow phenomenon resulting from rectal irritation with mucus and fluid production.
      • Ouslander J.G.
      • Schnelle J.F.
      Incontinence in the nursing home.
      In addition, rectal distension may lead to relaxation of the internal sphincter, further enhancing the risk of fecal soiling.
      • Muller-Lissner S.
      General geriatrics and gastroenterology: constipation and faecal incontinence.
      • Scarlett Y.
      Medical management of fecal incontinence.
      The pathophysiology of fecal incontinence also was described by Read and Abouzekry,
      • Read N.W.
      • Abouzekry L.
      Why do patients with faecal impaction have faecal incontinence.
      who showed that compared with controls, impacted patients had significantly impaired anorectal sensation, preventing conscious contraction of the external sphincter when the internal sphincter is relaxed.
      The appropriate management of chronic constipation may prevent fecal impaction and, hence, fecal incontinence. Studies by Chassagne et al
      • Chassagne P.
      • Jego A.
      • Gloc P.
      • et al.
      Does treatment of constipation improve faecal incontinence in institutionalized elderly patients?.
      and Tobin and Brocklehurst
      • Tobin G.W.
      • Brocklehurst J.C.
      Faecal incontinence in residential homes for the elderly: prevalence, aetiology and management.
      both indicated that patients in full compliance with treatment who had complete rectal emptying had substantially decreased episodes of fecal incontinence.

       Colonic Disease

      In addition to the anorectal comorbidities described earlier, there have been a number of studies that showed a possible association between constipation and the development of colorectal cancer, megacolon, volvulus, and diverticular disease.

       Colorectal cancer

      The association between constipation and colorectal cancer risk has been a highly controversial subject, with studies to date providing inconsistent evidence.
      Sonnenberg and Muller
      • Sonnenberg A.
      • Muller A.D.
      Constipation and cathartics as risk factors of colorectal cancer: a meta-analysis.
      conducted a systematic review of 9 case-control studies, published before 1992, evaluating risk factors for colorectal cancer such as self-reported constipation or bowel movement frequency.
      • Sonnenberg A.
      • Muller A.D.
      Constipation and cathartics as risk factors of colorectal cancer: a meta-analysis.
      The review revealed that symptoms of constipation were associated with a significant increased risk of colorectal cancer, with an odds ratio of 1.48 (95% confidence interval, 1.32–1.66). However, colon cancer can cause constipation so this may be an example of “reverse causality”. Subsequent case-control studies have both retrospectively and prospectively examined the possible effect of constipation on colorectal cancer incidence, yielding mixed results
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      • Jacobs E.J.
      • White E.
      Constipation, laxative use, and colon cancer among middle-aged adults.
      • Roberts M.C.
      • Millikan R.C.
      • Galanko J.A.
      • et al.
      Constipation, laxative use, and colon cancer in a North Carolina population.
      • Watanabe T.
      • Nakaya N.
      • Kurashima K.
      • et al.
      Constipation, laxative use and risk of colorectal cancer: the Miyagi Cohort Study.
      • Kojima M.
      • Wakai K.
      • Tokudome S.
      • et al.
      Bowel movement frequency and risk of colorectal cancer in a large cohort study of Japanese men and women.
      • Dukas L.
      • Willett W.C.
      • Colditz G.A.
      • et al.
      Prospective study of bowel movement, laxative use, and risk of colorectal cancer among women.
      • Chan A.O.
      • Hui W.M.
      • Leung G.
      • et al.
      Patients with functional constipation do not have increased prevalence of colorectal cancer precursors.
      • Otani T.
      • Iwasaki M.
      • Inoue M.
      • et al.
      Bowel movement, state of stool, and subsequent risk for colorectal cancer: the Japan public health center-based prospective study.
      • Nascimbeni R.
      • Donato F.
      • Ghirardi M.
      • et al.
      Constipation, anthranoid laxatives, melanosis coli, and colon cancer: a risk assessment using aberrant crypt foci.
      (Table 1, Table 5).
      Table 5Studies of Constipation and Colorectal Cancer
      StudyMethodsSubjectsFindingsConstipation criteria
      Jacobs and White,
      • Jacobs E.J.
      • White E.
      Constipation, laxative use, and colon cancer among middle-aged adults.
      1998
      Retrospective case-control study424 with colon cancer, 414 controls (US)Colon cancer RR of 2.0 (95% CI, 1.2–3.6) for constipation 12–51 times/y, RR of 4.4 (2.1–8.9) for constipation >52 times/yFeeling constipated to the point of having to take something
      Roberts et al,
      • Roberts M.C.
      • Millikan R.C.
      • Galanko J.A.
      • et al.
      Constipation, laxative use, and colon cancer in a North Carolina population.
      2003
      Retrospective, population-based, case-control study643 with colon cancer, 1048 controls (US)Constipation associated with 2-fold risk of colon cancer (OR, 2.36; 95% CI, 1.41–3.93)<3 BMs/wk
      Watanabe et al,
      • Watanabe T.
      • Nakaya N.
      • Kurashima K.
      • et al.
      Constipation, laxative use and risk of colorectal cancer: the Miyagi Cohort Study.
      2004
      Population-based, prospective cohort study (7 years of follow-up evaluation)41,670 subjects; 251 incident cases of colorectal cancer (Japan)With constipation, colorectal cancer RR of 1.35 (95% CI, 0.99–1.84)Fewer than daily BMs
      Kojima et al,
      • Kojima M.
      • Wakai K.
      • Tokudome S.
      • et al.
      Bowel movement frequency and risk of colorectal cancer in a large cohort study of Japanese men and women.
      2004
      Prospective cohort study62,929 subjects; 649 cases of colorectal cancer (Japan)Women with BM every 6 days or less versus ≥1 BM/d had IRR colorectal cancer: 2.47 (95% CI 1.01–6.01); colon cancer: 2.52 (95% CI, 0.93–6.82)BM every 6 days or less
      Dukas et al,
      • Dukas L.
      • Willett W.C.
      • Colditz G.A.
      • et al.
      Prospective study of bowel movement, laxative use, and risk of colorectal cancer among women.
      2000
      Prospective cohort study84,577 women; 611 incident cases of colorectal cancer (US)RR associated with BM every third day or less, compared with once daily BM: 0.94 (95% CI, 0.69–1.28) for colorectal cancerBM every third day or less
      Chan et al,
      • Chan A.O.
      • Hui W.M.
      • Leung G.
      • et al.
      Patients with functional constipation do not have increased prevalence of colorectal cancer precursors.
      2007
      Prospective case-control study; consecutive patients invited for screening colonoscopy220 with constipation, 235 controls (China)Constipation had no increased risk of colorectal cancer, measured by prevalence of colonic lesions on colonoscopyRome II criteria
      Otani et al,
      • Otani T.
      • Iwasaki M.
      • Inoue M.
      • et al.
      Bowel movement, state of stool, and subsequent risk for colorectal cancer: the Japan public health center-based prospective study.
      2006
      Ongoing cohort study57,940 subjects; 479 cases of colorectal cancer (Japan)Low frequency BMs not associated with colorectal cancer: hazard ratio of 0.97 (95% CI, 0.61–1.55) in men; hazard ratio of 0.75 (95% CI, 0.49–1.13) in women2–3 BMs/wk
      Nascimbeni et al,
      • Nascimbeni R.
      • Donato F.
      • Ghirardi M.
      • et al.
      Constipation, anthranoid laxatives, melanosis coli, and colon cancer: a risk assessment using aberrant crypt foci.
      2002
      Prospective study of surgical patients55 patients with sigmoid cancer, 41 patients with diverticular disease, 96 controls (Italy)Aberrant crypt foci frequency did not vary with constipation historyRome criteria
      RR, relative risk; CI, confidence interval; OR, odds ratio; BM, bowel movement; IRR, incident rate ratio.
      The postulated causal link between constipation and increased colon cancer risk is that longer transit times increase the duration of contact between the colonic mucosa and concentrated carcinogens in the lumen.
      • Jacobs E.J.
      • White E.
      Constipation, laxative use, and colon cancer among middle-aged adults.
      • Burkitt D.P.
      Epidemiology of cancer of the colon and rectum.
      Possible carcinogenic agents within stool include bile acids,
      • Narisawa T.
      • Magadia N.E.
      • Weisburger J.H.
      • et al.
      Promoting effect of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N'-nitro-N-nitrosoguanidine in rats.
      • Reddy B.S.
      • Watanabe K.
      • Weisburger J.H.
      • et al.
      Promoting effect of bile acids in colon carcinogenesis in germ-free and conventional F344 rats.
      fecapentaene-12,
      • Clinton S.K.
      • Bostwick D.G.
      • Olson L.M.
      • et al.
      Effects of ammonium acetate and sodium cholate on N-methyl-N'-nitro-N-nitrosoguanidine-induced colon carcinogenesis of rats.
      and ammonium acetate.
      • Zarkovic M.
      • Qin X.
      • Nakatsuru Y.
      • et al.
      Tumor promotion by fecapentaene-12 in a rat colon carcinogenesis model.
      It also has been hypothesized that the increased use of laxatives potentially may increase the risk of colon cancer. However, to date, studies of this association have not yielded convincing results.
      • Sonnenberg A.
      • Muller A.D.
      Constipation and cathartics as risk factors of colorectal cancer: a meta-analysis.
      • Jacobs E.J.
      • White E.
      Constipation, laxative use, and colon cancer among middle-aged adults.
      • Roberts M.C.
      • Millikan R.C.
      • Galanko J.A.
      • et al.
      Constipation, laxative use, and colon cancer in a North Carolina population.
      • Watanabe T.
      • Nakaya N.
      • Kurashima K.
      • et al.
      Constipation, laxative use and risk of colorectal cancer: the Miyagi Cohort Study.
      • Kojima M.
      • Wakai K.
      • Tokudome S.
      • et al.
      Bowel movement frequency and risk of colorectal cancer in a large cohort study of Japanese men and women.
      • Nascimbeni R.
      • Donato F.
      • Ghirardi M.
      • et al.
      Constipation, anthranoid laxatives, melanosis coli, and colon cancer: a risk assessment using aberrant crypt foci.

       Megacolon

      Chronic megacolon may represent the end stage of any form of refractory constipation or may be a primary colonic disease; most adults with idiopathic megacolon have a long-standing history of constipation.
      • Bharucha A.E.
      • Phillips S.F.
      Megacolon: acute, toxic, and chronic.
      In fact, Singh et al
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      found patients were 5 times more likely to have a diagnosis of megacolon after, versus before, a diagnosis of constipation (Table 1). There is some evidence to show that patients with megacolon, compared with those without, were significantly more likely to be constipated, as determined by a scoring system applied to plain abdominal radiographs (relative risk, 1.26; 95% confidence interval, 1.0–1.5, by univariate analysis).
      • Harari D.
      • Minaker K.L.
      Megacolon in patients with chronic spinal cord injury.
      This study did not establish a causal relationship; nonetheless, it provides an association between objectively confirmed constipation and megacolon.

       Volvulus

      Sigmoid volvulus is a common cause of large-bowel obstruction. The cause of volvulus is multifactorial and is more common in individuals with long-standing megacolon.
      • Waseem M.
      • Hipp A.
      Megacolon: constipation or volvulus?.
      • Friedman J.D.
      • Odland M.D.
      • Bubrick M.P.
      Experience with colonic volvulus.
      Studies conducted to date have shown that a diagnosis of volvulus is significantly more common in the context of a diagnosis of constipation
      • Singh G.
      • Kahler K.
      • Bharathi V.
      • et al.
      Constipation in adults: complications and comorbidities.
      • Singh G.
      • Vadhavkar S.
      • Wang H.
      • et al.
      Complications and comorbidities of constipation in adults.
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      (Table 1). Specifically, Tiah and Goh
      • Tiah L.
      • Goh S.H.
      Sigmoid volvulus: diagnostic twists and turns.
      reported that as many as 60% of volvulus patients had a history of constipation, and Mitra et al
      • Mitra D.
      • Davis K.L.
      • Baran R.W.
      Healthcare costs and clinical sequelae associated with constipation in a managed care population.
      found that a diagnosis of constipation increased the risk of developing volvulus by 10-fold.

       Diverticular disease

      Diverticulosis is proposed to be a condition resulting from westernization and the adoption of reduced-fiber diets.
      • Painter N.S.
      • Burkitt D.P.
      Diverticular disease of the colon: a deficiency disease of Western civilization.
      Examination of an existing hypothesis for diverticulosis pathophysiology illustrates a plausible role for constipation. Longer transit times and smaller stool volumes are associated with an increase in intraluminal pressure and segmentation, which may in turn lead to pulsion diverticula development at points of weakness in the colonic wall.
      • Painter N.S.
      • Burkitt D.P.
      Diverticular disease of the colon: a deficiency disease of Western civilization.
      • Painter N.S.
      • Truelove S.C.
      • Ardran G.M.
      • et al.
      Segmentation and the localization of intraluminal pressures in the human colon, with special reference to the pathogenesis of colonic diverticula.
      • Truelove S.C.
      Movements of the large intestine.
      • Ferzoco L.B.
      • Raptopoulos V.
      • Silen W.
      Acute diverticulitis.
      • Burkitt D.P.
      • Walker A.R.
      • Painter N.S.
      Effect of dietary fibre on stools and the transit-times, and its role in the causation of disease.
      Stollman and Raskin
      • Stollman N.
      • Raskin J.B.
      Diverticular disease of the colon.
      suggested that abnormal colonic motility observed in constipation also may play a pathophysiologic role. The relative role of constipation is still unclear, and probably represents the coexistence of 2 common diseases (Table 1).

       Extracolonic

      The most developed literature on extracolonic comorbidities exists for constipation and urinary tract pathology.

       Urologic disorders

      Retrospective as well as prospective studies in pediatrics and adults are suggestive of constipation playing an etiologic role in urinary tract infections, enuresis, and urinary incontinence
      • Romanczuk W.
      • Korczawski R.
      Chronic constipation: a cause of recurrent urinary tract infections.
      • Neumann P.Z.
      • DeDomenico I.J.
      • Nogrady M.B.
      Constipation and urinary tract infection.
      • Anagnostopoulos D.
      • Mavromihalis J.
      • Markantonatos A.
      • et al.
      Constipation: a cause of enuresis.
      • O'Regan S.
      • Yazbeck S.
      • Schick E.
      Constipation, bladder instability, urinary tract infection syndrome.
      • O'Regan S.
      • Yazbeck S.
      • Hamberger B.
      • et al.
      Constipation a commonly unrecognized cause of enuresis.
      • Loening-Baucke V.
      Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood.
      • Blethyn A.J.
      • Jenkins H.R.
      • Roberts R.
      • et al.
      Radiological evidence of constipation in urinary tract infection.
      • Kasirga E.
      • Akil I.
      • Yilmaz O.
      • et al.
      Evaluation of voiding dysfunctions in children with chronic functional constipation.
      • Loening-Baucke V.
      Prevalence rates for constipation and faecal and urinary incontinence.
      • Koskimaki J.
      • Hakama M.
      • Huhtala H.
      • et al.
      Association of non-urological diseases with lower urinary tract symptoms.
      • Aggazzotti G.
      • Pesce F.
      • Grassi D.
      • et al.
      Prevalence of urinary incontinence among institutionalized patients: a cross-sectional epidemiologic study in a midsized city in northern Italy.
      • Oskay U.Y.
      • Beji N.K.
      • Yalcin O.
      A study on urogenital complaints of postmenopausal women aged 50 and over.
      (Table 6).
      Table 6Studies of Constipation and Urologic Disorders
      StudyMethodsSubjectsFindingsConstipation criteria
      UTI
       Neumann et al,
      • Neumann P.Z.
      • DeDomenico I.J.
      • Nogrady M.B.
      Constipation and urinary tract infection.
      1973
      Prospective study of random group presenting with UTI, plus treatment intervention131 pediatric patients with UTI (Canada)34% of children presenting for UTI had abnormal bowel habits plus radiologic changes related to long-standing fecal retention
      Criteria were as follows: firm hard stools with difficulty passing, days skipped between BMs, blood-streaked stools from rectal fissures, prolonged extensive use of laxatives and/or suppositories, abnormally large sized BMs, or fecal soiling.
       O'Regan et al,
      • O'Regan S.
      • Yazbeck S.
      • Schick E.
      Constipation, bladder instability, urinary tract infection syndrome.
      1985
      Prospective study with physical testing47 pediatric patients with recurrent UTI (Canada)Children with recurrent UTI were noted to have large fecal reservoirs by rectal examination and manometryQuestioning of parents, criteria not further specified
       Blethyn et al,
      • Blethyn A.J.
      • Jenkins H.R.
      • Roberts R.
      • et al.
      Radiological evidence of constipation in urinary tract infection.
      1995
      Retrospective case-control chart review61 pediatric patients referred for investigation of UTI (Wales)Significant association between degree of fecal loading and number of UTIs (r = 0.24, P < .05)Fecal loading using a radiologic scoring system
       Romanczuk et al,
      • Romanczuk W.
      • Korczawski R.
      Chronic constipation: a cause of recurrent urinary tract infections.
      1993
      Prospective study with physical testing and treatment intervention180 pediatric patients hospitalized for CC (Poland)Recurrent UTIs in 39% of children hospitalized for CC (66% of girls; 25% of boys)Interview, clinical symptoms, physical examination including rectal palpation, and endoscopy of the large bowel, rectoscopy, and/or sigmoidoscopy
      Additional radiologic examinations were performed in some cases.
       Kasirga et al,
      • Kasirga E.
      • Akil I.
      • Yilmaz O.
      • et al.
      Evaluation of voiding dysfunctions in children with chronic functional constipation.
      2006
      Prospective study with physical testing38 pediatric patients with CC, 31 controls (Turkey)UTI and urgency higher in children with CC versus controls (42.1% vs 19.4%, P < .05 and 26.9% vs 4%, P < .05, respectively)Painful defecation with hard stools less than 3 times/wk for ≥6 mo
      Enuresis
       Anagnostopoulous et al,
      • Anagnostopoulos D.
      • Mavromihalis J.
      • Markantonatos A.
      • et al.
      Constipation: a cause of enuresis.
      1989
      Prospective study with physical testing and treatment intervention35 pediatric patients (26 with enuresis, 9 with severe functional constipation without urinary symptoms) (Greece)CC was confirmed in 20 of 26 children with enuresis, all had uninhibited bladder contractions on urodynamic testing
      Criteria were as follows: (1) more than a 72-hour interval between BMs or less than 3/wk, (2) secondary encopresis, (3) passage of small, hard, scibalous stools, (4) poor emptying and dilatation of the rectal ampulla after defecation as determined by rectal examination, (5) decreased amplitude of the rectoanal inhibitory reflex, and (6) markedly unstable pressures in the upper anal canal with changes exceeding 25 cm H20.
       O'Regan et al,
      • O'Regan S.
      • Yazbeck S.
      • Hamberger B.
      • et al.
      Constipation a commonly unrecognized cause of enuresis.
      1986
      Prospective study with physical testing and treatment intervention29 pediatric patients (25 with enuresis, 4 with severe functional constipation without urinary symptoms) (Canada)Constipation confirmed in 22 of 25 enuretic patients; all 19 of 22 enuretic patients with urodynamic studies had uninhibited bladder contractions
      Criteria were as follows: (1) more than a 72-hour interval between BMs, (2) overflow incontinence/encopresis, (3) passage of small, hard, scibalous stools with intermittent passage of large stools, (4) poor emptying and dilatation of the rectal ampulla after defecation as determined by rectal examination, and (5) grossly decreased level of perception and increased tolerance to balloon insufflation during rectal manometry combined with any element of the 4 alone.
      Urinary incontinence
       Loening-Baucke,
      • Loening-Baucke V.
      Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood.
      1997
      Prospective study with treatment intervention234 consecutive pediatric patients with functional constipation and encopresis (US)Of patients with functional constipation or encopresis: 29% complained of daytime UI, 34% of nighttime UIFunctional constipation not caused by organic disease or medication
       Loening-Baucke,
      • Loening-Baucke V.
      Prevalence rates for constipation and faecal and urinary incontinence.
      2006
      Retrospective chart review482 pediatric patients (US)Significantly more UI in constipated (21.8%) versus nonconstipated children (7.3%) (χ2 = 15.17, P < .01)
      Criteria were 2 or more for 8 weeks: less than 3 BMs/wk, more than 1 episode of FI/wk, large stools in rectum or felt on abdominal examination or passed and obstructed the toilet, retentive posturing, or painful defecation.
       Koskimaki et al,
      • Koskimaki J.
      • Hakama M.
      • Huhtala H.
      • et al.
      Association of non-urological diseases with lower urinary tract symptoms.
      2001
      Population-based study1963 men ages 50, 60, and 70 years (Finland)Significant association between lower urinary tract symptoms and constipation (OR, 2.3; 95% CI, 1.5–3.3)Listed on medical history questionnaire
       Aggazzotti et al,
      • Aggazzotti G.
      • Pesce F.
      • Grassi D.
      • et al.
      Prevalence of urinary incontinence among institutionalized patients: a cross-sectional epidemiologic study in a midsized city in northern Italy.
      2000
      Cross-sectional study of 14 residential or nursing homes839 adults (Italy)Of those with constipation, 72.7% had UI, versus 46.5% without (P < .01)Listed in clinical record
       Charach et al,
      • Charach G.
      • Greenstein A.
      • Rabinovich P.
      • et al.
      Alleviating constipation in the elderly improves lower urinary tract symptoms.
      2001
      Prospective cohort study with treatment intervention52 elderly patients (Israel)Constipation treatment decreased residual urine volume (85 ± 39.5 to 30 ± 22.56 mL, P < .01); decreased the number of patients with bacteriurial events (P < .01); KCI between urinary residue and BMs/wk was -0.46 (P < .01)Hard stool with <3 BMs/wk
       Erickson et al,
      • Erickson B.A.
      • Austin J.C.
      • Cooper C.S.
      • et al.
      Polyethylene glycol 3350 for constipation in children with dysfunctional elimination.
      2003
      Retrospective review of treatment intervention46 pediatric patients with dysfunctional elimination (US)Constipation treatment improved UI (P = .05); patients with resolved constipation had lower postvoid residual versus with constipation (11.8% vs 30.6%; P < .01)History of infrequent BMs (less than every other day) and/or hard, large or painful BMs (most also had abdominal radiograph confirmation)
       Oskay et al,
      • Oskay U.Y.
      • Beji N.K.
      • Yalcin O.
      A study on urogenital complaints of postmenopausal women aged 50 and over.
      2005
      Prospective interview500 postmenopausal women (Turkey)CC significantly increased risk of UI (RR, 1.75; 95% CI, 1.17–2.65)Patient report on interview
      UTI, urinary tract infection; CC, chronic constipation; UI, urinary incontinence; OR, odds ratio; CI, confidence interval; KCI, Kendall Correlation Index; BM, bowel movement; RR, relative risk.
      a Criteria were as follows: firm hard stools with difficulty passing, days skipped between BMs, blood-streaked stools from rectal fissures, prolonged extensive use of laxatives and/or suppositories, abnormally large sized BMs, or fecal soiling.
      b Additional radiologic examinations were performed in some cases.
      c Criteria were as follows: (1) more than a 72-hour interval between BMs or less than 3/wk, (2) secondary encopresis, (3) passage of small, hard, scibalous stools, (4) poor emptying and dilatation of the rectal ampulla after defecation as determined by rectal examination, (5) decreased amplitude of the rectoanal inhibitory reflex, and (6) markedly unstable pressures in the upper anal canal with changes exceeding 25 cm H20.
      d Criteria were as follows: (1) more than a 72-hour interval between BMs, (2) overflow incontinence/encopresis, (3) passage of small, hard, scibalous stools with intermittent passage of large stools, (4) poor emptying and dilatation of the rectal ampulla after defecation as determined by rectal examination, and (5) grossly decreased level of perception and increased tolerance to balloon insufflation during rectal manometry combined with any element of the 4 alone.
      e Criteria were 2 or more for 8 weeks: less than 3 BMs/wk, more than 1 episode of FI/wk, large stools in rectum or felt on abdominal examination or passed and obstructed the toilet, retentive posturing, or painful defecation.
      A mechanical explanation for constipation causing urinary dysfunction centers around the anatomic distortion and displacement of the bladder by a rectum and sigmoid colon loaded with feces.
      • Anagnostopoulos D.
      • Mavromihalis J.
      • Markantonatos A.
      • et al.
      Constipation: a cause of enuresis.
      • O'Regan S.
      • Yazbeck S.
      • Hamberger B.
      • et al.
      Constipation a commonly unrecognized cause of enuresis.
      This compression of the bladder may cause stimulation of stretch receptors, resulting in uninhibited bladder contractions, which are common to vesico-ureteral reflux, recurrent urinary tract infection, and enuresis.
      • O'Regan S.
      • Yazbeck S.
      • Schick E.
      Constipation, bladder instability, urinary tract infection syndrome.
      Studies incorporating physical testing
      • Romanczuk W.
      • Korczawski R.
      Chronic constipation: a cause of recurrent urinary tract infections.
      • Anagnostopoulos D.
      • Mavromihalis J.
      • Markantonatos A.
      • et al.
      Constipation: a cause of enuresis.
      • O'Regan S.
      • Yazbeck S.
      • Schick E.
      Constipation, bladder instability, urinary tract infection syndrome.
      • O'Regan S.
      • Yazbeck S.
      • Hamberger B.
      • et al.
      Constipation a commonly unrecognized cause of enuresis.
      • Kasirga E.
      • Akil I.
      • Yilmaz O.
      • et al.
      Evaluation of voiding dysfunctions in children with chronic functional constipation.
      and/or treatment intervention
      • Romanczuk W.
      • Korczawski R.
      Chronic constipation: a cause of recurrent urinary tract infections.
      • Neumann P.Z.
      • DeDomenico I.J.
      • Nogrady M.B.
      Constipation and urinary tract infection.
      • Anagnostopoulos D.
      • Mavromihalis J.
      • Markantonatos A.
      • et al.
      Constipation: a cause of enuresis.
      • O'Regan S.
      • Yazbeck S.
      • Hamberger B.
      • et al.
      Constipation a commonly unrecognized cause of enuresis.
      • Loening-Baucke V.
      Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood.
      • Erickson B.A.
      • Austin J.C.
      • Cooper C.S.
      • et al.
      Polyethylene glycol 3350 for constipation in children with dysfunctional elimination.
      • Charach G.
      • Greenstein A.
      • Rabinovich P.
      • et al.
      Alleviating constipation in the elderly improves lower urinary tract symptoms.
      • Dohil R.
      • Roberts E.
      • Jones K.V.
      • et al.
      Constipation and reversible urinary tract abnormalities.
      mechanistically support constipation's pathophysiologic mass effects on the urinary system, as well as its resolution with the treatment of constipation (Table 6). Collectively, these data support a causal relationship between constipation and urologic disorders.

      Conclusions

      The evidence of a cause-and-effect relationship between constipation and comorbid diseases is inferred from association studies and knowledge of the mechanical effects of constipation. However, in some cases there are confounding factors that may predispose to both constipation and comorbid diseases. For example, disruption of the enteric nervous system can lead to motility disorders, with secondary reduction in bowel movement frequency and colonic dilatation. Furthermore, lifestyle factors (eg, a diet low in fiber) may explain the overlap of constipation with disorders such as colorectal cancer and diverticular disease. The gastrointestinal and extraintestinal effects of other luminal factors, such as microbiota, continue to be evaluated.
      • Backhed F.
      • Ding H.
      • Wang T.
      • et al.
      The gut microbiota as an environmental factor that regulates fat storage.
      • Backhed F.
      • Ley R.E.
      • Sonnenburg J.L.
      • et al.
      Host-bacterial mutualism in the human intestine.
      • Backhed F.
      • Manchester J.K.
      • Semenkovich C.F.
      • et al.
      Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.
      • Turnbaugh P.J.
      • Ley R.E.
      • Mahowald M.A.
      • et al.
      An obesity-associated gut microbiome with increased capacity for energy harvest.
      Finally, the impact of childbirth on pelvic floor and anorectal function can be difficult to quantitate but may help explain in part gender differences in constipation. Additional studies analyzing such gender effects, as well as ethnobiological influences on constipation as a disorder, are warranted.
      Also, there is clearly the need for additional studies and for a better understanding of the economic and medical implications of other disorders potentially associated with constipation, which are beyond the scope of this review. Generally, studies suggest frequent symptom overlap between functional constipation and other functional gastrointestinal disorders such as the irritable bowel syndrome, and indeed symptom criteria may poorly distinguish these conditions.
      • Frissora C.L.
      • Koch K.L.
      Symptom overlap and comorbidity of irritable bowel syndrome with other conditions.
      • Talley N.J.
      • Weaver A.L.
      • Zinsmeister A.R.
      • et al.
      Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal disorders.
      Emerging data support brain–gut interactions that seem to explain the clinical association between gut symptoms, visceral pain hypersensitivity, and mood disorders.
      • Longstreth G.F.
      • Thompson W.G.
      • Chey W.D.
      • et al.
      Functional bowel disorders.
      However, much less is known about the mechanisms behind the association between functional gastrointestinal syndromes and conditions such as migraine, fibromyalgia, and chronic fatigue syndrome. We found only one case-control study examining comorbid extraintestinal functional disorders in which a significant association between constipation and fibromyalgia was observed.
      • Waylonis G.W.
      • Heck W.
      Fibromyalgia syndrome New associations.
      The relationship between obesity and constipation has been investigated in pediatric and adult populations with varying results; findings range from a negative association
      • Talley N.J.
      • Howell S.
      • Poulton R.
      Obesity and chronic gastrointestinal tract symptoms in young adults: a birth cohort study.
      to a positive association of the 2 disorders,
      • Pashankar D.S.
      • Loening-Baucke V.
      Increased prevalence of obesity in children with functional constipation evaluated in an academic medical center.
      including even a possibility of obesity distinguishing a more refractory-constipated patient population.
      • Misra S.
      • Lee A.
      • Gensel K.
      Chronic constipation in overweight children.
      Perhaps the most striking implication of this review is the overall burden of potential constipation comorbidities. Although for most, constipation may represent little more than a collection of nuisance symptoms, in others, constipation may lead to or indicate an increased risk for more serious complications. The relative role and synergy of environmental factors, colonic motility disorders, as well as constipation therapies must be considered in future research. Ultimately, realization of the disease risks associated with chronic constipation may provide the impetus needed to direct new research and shift attention on the part of patients and practitioners to methods for preventing significant and costly medical problems.

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