changes in bowel symptoms 1 year after rectocele repair
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Changes in bowel symptoms 1 year after rectocele repairVivian W. Sung, MD, MPH; Charles R. Rardin, MD; Christina A. Raker, ScD; Christine A. LaSala, MD; Deborah L. Myers, MD
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OBJECTIVE: We sought to evaluate changes in bowel symptoms afterrectocele repair and identify risk factors for persistent symptoms.
STUDY DESIGN: We conducted ancillary analysis of a randomized sur-ical trial for rectocele repair. Subjects underwent examinations andompleted questionnaires for bowel symptoms at baseline and 12onths postoperatively. Outcomes included resolution, persistence, or
e novo bowel symptoms. We used multiple logistic regression to iden-ify risk factors for bowel symptom persistence.
RESULTS: A total of 160 women enrolled: 139 had baseline bowel
symptoms and 85% had 12-month data. The prevalence of bowelCite this article as: Sung VW, Rardin CR, Raker CA, et al. Changes in bowel symptom
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symptoms decreased after rectocele repair (56% vs 23% splinting,74% vs 37% straining, 85% vs 19% incomplete evacuation, 66% vs14% obstructive defecation; P � .001 for all). On multiple logistic re-ression, a longer history of splinting was a risk factor for persistentostoperative splinting (adjusted odds ratio, 2.25; 95% confidence in-erval, 1.02–4.93).
CONCLUSION: Bowel symptoms may improve after rectocele repair,but almost half of women will have persistent symptoms.
Key words: bowel dysfunction, graft augmentation, posterior
colporrhaphy, randomized trial, rectoceles 1 year after rectocele repair. Am J Obstet Gynecol 2012;207:423.e1-5.
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Bowel symptoms and defecatory dys-function are common in women
ith pelvic floor disorders.1 The termdefecatory dysfunction” broadly in-ludes the need for excessive straining,anual manipulation, the sensation of
ncomplete evacuation, and the sensa-ion of obstructed defecation. Pelvic or-an prolapse has been reported to be a
From the Division of Urogynecology,Department of Obstetrics and Gynecology,Alpert Medical School of Brown University (DrsSung, Rardin, and Myers), and the Division ofResearch, Department of Obstetrics andGynecology, Women and Infants Hospital ofRhode Island (Dr Raker), Providence, RI, andthe Department of Obstetrics and Gynecology,Hartford Hospital, Hartford, CT (Dr LaSala).
Received Jan. 10, 2012; revised April 30,2012; accepted June 27, 2012.
V.W.S. is supported by grant numberK23HD060665 from the Eunice Kennedy
hriver National Institute of Child Health anduman Development.
he content is solely the responsibility of theuthors and does not necessarily represent thefficial views of the Eunice Kennedy Shriverational Institute of Child Health and Humanevelopment or the National Institutes ofealth.
he authors report no conflict of interest.
resented at the 38th Annual Scientificeeting of the Society of Gynecologicurgeons, Baltimore, MD, April 13-15, 2012.
eprints not available from the authors.
0002-9378/$36.00© 2012 Mosby, Inc. All rights reserved.
isk factor for bowel symptoms2,3 and itis estimated that 67-80% of women withpelvic organ prolapse also report defeca-tory symptoms.4-6
The underlying cause of defecatorysymptoms may include structural disor-ders (eg, rectocele, rectal prolapse), func-tional disorders (eg, dyssynergic defeca-tion, metabolic disorders), or even a“normal” range of bowel habits. On clinicalexamination, patients with these bowelsymptoms may have posterior vaginal wallprolapse or rectocele. However, many stud-ies have not confirmed an association be-tween the severity of posterior vaginal pro-lapse and increasing bowel symptomprevalence or severity.3,7,8 In addition, sur-gery for rectocele does not always lead to res-olution of the bowel symptoms.9,10 A study
y Gustilo-Ashby et al11 concluded that res-lutionorimprovementinbowelsymptomsan be expected after rectocele repair; how-ver, up to 35% of their patients reportedersistent or worsening bowel symptomsostoperatively. We previously found thatp to 45% of women who participated in aandomized trial of graft-augmented vs na-ive tissue rectocele repair also reported per-istent defecatory symptoms.12 Therefore,
ore information on the effect of rectoceleepair on bowel symptoms and predictorsre needed to most appropriately counselomen regarding expectations after recto-
ele repair.The primary objective of this study
es in bowel symp-
NOVEMBER 2012 Americ
oms 1 year after rectocele repair. Ourecondary objective was to identify riskactors for persistent and/or worseningowel symptoms.
MATERIALS AND METHODSWe performed a planned ancillary anal-ysis of 160 women enrolled in a random-ized, double-masked controlled trial ofporcine subintestinal submucosal graft-augmented rectocele repair vs native tis-sue repair. The details and methods forthis trial have been previously pub-lished.12 This ancillary analysis includesthe subset of women who reported base-line bowel symptoms. The study wasconducted at 2 sites: Women and InfantsHospital of Rhode Island in Providence,and Hartford Hospital in Connecticut,and the protocol was approved by bothinstitutional review boards. Patients andoutcome assessors were masked to ran-domization assignment. All women pro-vided written informed consent. Nofunding or support was provided by themanufacturer of the graft for any portionof the study.
As previously described, women withsymptomatic stage II rectocele electingsurgical repair were eligible. Other con-comitant vaginal prolapse repairs andantiincontinence procedures were al-lowed. Women �18 years of age; under-going concomitant sacrocolpopexy orcolorectal procedures; with a history of
porcine allergy, connective tissue dis-an Journal of Obstetrics & Gynecology 423.e1
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ease, pelvic malignancy, or pelvic radia-tion; or who did not speak English wereexcluded.
All women underwent a complete his-tory and physical examination, includ-ing the Pelvic Organ Prolapse Quantifi-cation examination in a 30-degree supinelithotomy position at baseline and 12months postoperatively.13 All women alsoompleted a self-administered symptomuestionnaire at baseline and 12 monthsostoperatively, which included relevant
tems from the Pelvic Floor Distress Inven-ory (PFDI)-20.14 Although “abnormal”
bowel behavior can encompass a widerange of symptoms, the American Collegeof Gastroenterology defines constipationas “unsatisfactory defecation characterizedby infrequent bowel movement, difficultstool passage, or both, with difficult stool
TABLE 1Demographic and clinical charactewith baseline bowel symptoms (n �
Variable
Mean age, y (SD)...................................................................................................................
Preoperative rectocele stage, n (%)..........................................................................................................
II..........................................................................................................
III..........................................................................................................
IV...................................................................................................................
Median preoperative POP-Q measurements, c..........................................................................................................
Point AP..........................................................................................................
Point BP..........................................................................................................
GH..........................................................................................................
PB...................................................................................................................
Postoperative rectocele stage, n (%)..........................................................................................................
0..........................................................................................................
I..........................................................................................................
II..........................................................................................................
III..........................................................................................................
IV...................................................................................................................
Median postoperative POP-Q measurements,..........................................................................................................
Point AP..........................................................................................................
Point BP..........................................................................................................
GH..........................................................................................................
PB...................................................................................................................
Numbers may not add to 100% because of missing data.POP-Q, Pelvic Organ Prolapse Quantification.
Sung. Bowel symptoms after rectocele repair. Am J Obstet
passage including straining, sense of in- i
423.e2 American Journal of Obstetrics & Gynecolo
complete evacuation, hard/lumpy stool,prolonged time to defecate, or need formanual maneuvers.”15 Therefore, we in-luded bowel symptoms of splintingPFDI item #4), straining (PFDI item #7),ncomplete evacuation (PFDI item #8),nd obstructed defecation (sensation thatstool gets trapped”). We also measurednal incontinence (inability to control gasnd/or stool). Women with affirmative re-ponses were asked additional detaileduestions regarding bowel symptom char-cteristics including the severity of bother,he frequency of occurrence of each bowelymptom (every day, �once/wk, once/k, once/mo, �once/mo), and durationf symptoms prior to surgery (�12onths, 1-2 years, �2 years).Women reporting any bowel symp-
om at baseline with 12-month data were
tics of women17)
56.2 (10.9)..................................................................................................................
..................................................................................................................
93 (79.5)..................................................................................................................
24 (20.5)..................................................................................................................
0..................................................................................................................
range)..................................................................................................................
0.0 (�1.0 to 4.0)..................................................................................................................
0.0 (�1.0 to 4.0)..................................................................................................................
4.0 (2.0–6.5)..................................................................................................................
3.5 (0.0–6.0)..................................................................................................................
..................................................................................................................
69 (61.1)..................................................................................................................
32 (28.3)..................................................................................................................
10 (8.9)..................................................................................................................
2 (1.8)..................................................................................................................
0..................................................................................................................
(range)..................................................................................................................
�3.0 (�3.0 to 3.0)..................................................................................................................
�3.0 (�3.0 to 3.0)..................................................................................................................
3.0 (0–5.0)..................................................................................................................
4.0 (0–6.0)..................................................................................................................
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ncluded in this analysis. We assessed
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hanges in bowel symptoms betweenaseline and 12 months postoperatively.e use the following definitions: resolu-
ion of symptoms (symptoms present ataseline that had completely resolved at2 months); persistence of symptomssymptoms that were present at baselinend either stayed the same or worsenedn severity of bother at 12 months); im-rovement of symptoms (symptoms thatere present at baseline and improved in
everity of bother at 12 months); and deovo symptoms (bowel symptoms thatere absent at baseline but present postop-
ratively). Student t tests were used toompare means between groups. We used
�2 for categorical variables. We comparedbaseline and 12-month changes in bowelsymptoms using McNemar test or Coch-ran-Mantel-Haenszel test to account forwithin-person comparisons. For womenreporting any degree of bowel symptomspostoperatively, we also evaluated in detailchanges in frequency of occurrence and se-verity of bother after rectocele repair. Weused multiple logistic regression to identifyrisk factors for persistent bowel symptomsat 12 months, constructing separate mod-els for straining, splinting, incompleteevacuation, and obstructed defecation.Variables based on the literature andthose that statistically changed our ef-fect estimates were included in ourmodels. P � .05 was considered statis-tically significant. Statistical analyseswere performed using software (SAS8.2; SAS Institute, Cary, NC).
RESULTSA total of 160 women were randomizedin this trial. All women received a recto-cele repair: 81 received native tissue re-pair and 79 received graft-augmentedrectocele repair. There was a high preva-lenceofat least1bowel symptom.Ofthe160women randomized, 139 (87%) had bowelsymptomsatbaseline and117(85%)ofthesehad12-monthdataandwereincludedinthisanalysis. At baseline, the mean age of womenwith bowel symptoms was 56.2 years (SD11), the majority (99%) were Caucasian,27% had undergone a prior urogynecologicprocedure, and 80% had stage II and 21%had stage III rectocele on baseline Pelvic Or-
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gan Prolapse Quantification. Of women,
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94% underwent concomitant procedures,including 13% who underwent vaginal hys-terectomy and vault suspension. Table 1presents additional clinical characteristics ofthe study population.
At baseline, 56% of women reportedmanual splinting; 74%, straining; 85%,incomplete evacuation; 66%, sensationof obstructed defecation; and 63%, analincontinence. Of women, 15% reportedhaving only 1 bowel symptom; 14%, 2bowel symptoms; 24%, 3 bowel symp-toms; 23%, 4 bowel symptoms; and 25%,all 5 bowel symptoms.
Changes in bowel symptoms are pre-sented in Table 2. At 12 months postsur-gery, the prevalence of all bowel symp-toms significantly decreased; however,23% of patients reported persistentsplinting; 37%, persistent straining; and19%, persistent incomplete evacuation(P � .001 for all). The prevalence of ob-tructed defecation also improved (14%)s did anal incontinence (26%) (P � .001or both). The total number of bowelymptoms reported postoperatively peratient also significantly decreased with9% now reporting 0 symptoms; 21%, 1ymptom; 23%, 2 symptoms; 16%, 3ymptoms; 10%, 4 symptoms; and �1%,bowel symptoms (P � .0001, data not
hown).Table 3 presents additional details re-
arding bowel symptom characteristicsor the women reporting unresolvedowel symptoms at 12 months (includeshose reporting symptoms improved,ame, or worse). The frequency of expe-iencing each symptom daily, weekly, oronthly significantly improved only for
he symptom of incomplete evacuation,lthough there were trends of improve-ent in frequency for all other bowel
ymptoms as well. Overall the severity ofother improved for splinting, straining,
ncomplete evacuation, and obstructedefecation.On multiple logistic regression (Table
), only longer duration of splinting wasrisk factor for persistent splinting (ad-
usted odds ratio, 2.25; 95% confidencenterval, 1.02– 4.93). Age, graft use, post-perative rectocele stage, and durationf symptoms were not significant risk fac-
orsforpersistentstraining,incompleteevac-
ation, or obstructed defecation.COMMENTBowel symptoms and anorectal dysfunc-tion cause significant bother, discomfort,and embarrassment to women. Tradition-ally, patients with bowel symptoms andclinical evidence of posterior vaginal pro-lapse were often treated with rectocele re-pair; however, although the vaginal bulgeis often repaired many still have persistentor recurrent bowel symptoms. In ourstudy, although many women reportedimprovement in symptom bother forbowel symptoms, up to 37% had at least1 persistent symptom at 1 year. Longerpreoperative duration of splinting was arisk factor for persistent splinting post-operatively. Postoperative rectocele stagewas not a risk factor for any persistentsymptom in our study.
What defines “normal” bowel habitsmay be debatable because a patient’s as-sessment may include the frequency ofbowel movements, the consistency orquantity of stools, and/or associatedqualitative symptoms. In a study byBellini et al16 including 140 subjects who
TABLE 2Changes in bowel symptoms after
Bowel symptom Baseline, n
Splinting 66 (57)
...................................................................................................................
Straining 80 (69)
...................................................................................................................
Incomplete evacuation 92 (80)
...................................................................................................................
Obstructed defecation 73 (66)
...................................................................................................................a Resolved� symptom present at baseline, absent postoperatively
postoperatively; improved � symptom present at baseline and pabsent at baseline, present postoperatively; b P � .001 for com
Sung. Bowel symptoms after rectocele repair. Am J Obstet
perceived their defecation behavior as p
NOVEMBER 2012 Americ
normal, stool frequency ranged from 3times per day to 3 times per week. Forwomen, only 6% reported the need tostrain, 6% reported incomplete evacua-tion, and 0% required manual maneu-vers for �25% of defecations. Thesefindings were supported in anotherstudy by Walter et al17 assessing normal
owel habits in 124 adults in the generalopulation who did not have any gas-rointestinal abnormality. The majority64%) had normal stool consistency �75%f the time. In addition, the authors con-luded that some degree of urgency (12%f normal population), straining (19% oformal population), and incompletevacuation (19% of normal popula-ion) should be considered normal.
Compared to these studies on normaleneral adult populations, the preva-ence of baseline bowel symptoms in ourtudy was high (84%) and this is consis-ent with other studies of women under-oing surgical treatment for prolapsend/or rectocele. In a secondary analysisf a randomized trial for 3 different ap-
tocele repair
) 12 mo postoperative, n (%)a
Persistent 15 (22.7)b.................................................................................
Resolved 40 (60.6).................................................................................
Improved 11 (16.7).................................................................................
De novo 0..................................................................................................................
Persistent 32 (36.8)b.................................................................................
Resolved 35 (40.2).................................................................................
Improved 13 (14.9).................................................................................
De novo 7 (8.1)..................................................................................................................
Persistent 19 (19.0)b.................................................................................
Resolved 50 (50.0).................................................................................
Improved 23 (23.0).................................................................................
De novo 8 (8.0)..................................................................................................................
Persistent 11 (14.3)b.................................................................................
Resolved 53 (68.8).................................................................................
Improved 9 (11.7).................................................................................
De novo 4 (5.2)..................................................................................................................
istent� symptom present at baseline, same or worse bothereratively, but improved bother severity; de novo � symptom
ison of baseline vs persistent postoperative symptoms.
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roaches to rectocele repair, the pres-
an Journal of Obstetrics & Gynecology 423.e3
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ence of at least 1 bowel symptom at base-line ranged from 80-97%.11 A study byBradley et al7 of women undergoing sa-
TABLE 3Bowel symptom details in womenpostoperative symptoms after rect
Bowel symptom and characteristic Ba
Splinting (n � 26)..........................................................................................................
Frequency.................................................................................................
Every day 8.................................................................................................
Once/wk to once/mo 15.................................................................................................
�Once/mo 3..........................................................................................................
Severity of bother.................................................................................................
Very 16.................................................................................................
Somewhat/moderate 7.................................................................................................
Not at all 3...................................................................................................................
Straining (n � 45)..........................................................................................................
Frequency.................................................................................................
Every day 8.................................................................................................
Once/wk to once/mo 30.................................................................................................
�Once/mo 7..........................................................................................................
Severity of bother.................................................................................................
Very 22.................................................................................................
Somewhat/moderate 21.................................................................................................
Not at all 2...................................................................................................................
Incomplete evacuation (n � 42)..........................................................................................................
Frequency.................................................................................................
Every day 14.................................................................................................
Once/wk to once/mo 26.................................................................................................
�Once/mo 2..........................................................................................................
Severity of bother.................................................................................................
Very 26.................................................................................................
Somewhat/moderate 16.................................................................................................
Not at all 0...................................................................................................................
Obstructed defecation (n � 20)..........................................................................................................
Frequency.................................................................................................
Every day 7.................................................................................................
Once/wk to once/mo 13.................................................................................................
�Once/mo 0..........................................................................................................
Severity of bother.................................................................................................
Very 11.................................................................................................
Somewhat/moderate 9.................................................................................................
Not at all 0...................................................................................................................
Numbers may not add to totals because of missing data. Comparison
Sung. Bowel symptoms after rectocele repair. Am J Obstet
rocolpopexy for vaginal vault prolapse s
423.e4 American Journal of Obstetrics & Gynecolo
ith or without rectocele repair reported45% prevalence of at least 1 bowel symp-
om. When the same cohort of women was
orting unresolvedle repair
ne 12 mo postoperative P value
..................................................................................................................
..................................................................................................................
.8) 4 (16.0)..................................................................................................................
.7) 13 (52.0)..................................................................................................................
.5) 8 (32.0) .06..................................................................................................................
..................................................................................................................
.5) 7 (26.9)..................................................................................................................
.9) 11 (42.3)..................................................................................................................
.5) 8 (30.8) .01..................................................................................................................
..................................................................................................................
..................................................................................................................
.8) 8 (18.2)..................................................................................................................
.7) 25 (56.8)..................................................................................................................
.6) 11 (25.0) .3..................................................................................................................
..................................................................................................................
.9) 12 (26.7)..................................................................................................................
.7) 31 (68.9)..................................................................................................................
) 2 (4.4) .03..................................................................................................................
..................................................................................................................
..................................................................................................................
.3) 6 (14.6)..................................................................................................................
.9) 30 (73.2)..................................................................................................................
) 5 (12.5) .08..................................................................................................................
..................................................................................................................
.9) 12 (28.6)..................................................................................................................
.1) 20 (47.6)..................................................................................................................
10 (23.8) � .0001..................................................................................................................
..................................................................................................................
..................................................................................................................
.0) 3 (15.0)..................................................................................................................
.0) 13 (65.0)..................................................................................................................
4 (20.0) .02..................................................................................................................
..................................................................................................................
.0) 7 (35.0)..................................................................................................................
.0) 10 (5.0)..................................................................................................................
3 (15.0) .1..................................................................................................................
cNemar test or Mantel-Haenszel test to account for paired data.
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eparated by whether a concurrent posterior
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rocedure was performed, the prevalence ofefecatory symptoms and severity scoresere higher in the group who underwentosterior procedures vs those who did not.6
Of note, 22% of that study population hadundergone previous rectocele repair.
There are few published large ran-domized trials specifically assessing def-ecatory outcomes after rectocele repair.Our findings are consistent with those ofGustilo-Ashby et al11 in that at 1 year afterransvaginal rectocele repair, women haveignificant improvement in bowel symp-oms; however, almost half of women haveome degree of persistent symptoms. Inur study, overall severity of bother im-roved for all symptoms; however, the fre-uency of experiencing these symptomsnly significantly decreased for the symp-om of obstructed defecation.
Outcomes after colorectal approacheso rectoceles do not appear to be signifi-antly better. In a small study of 48omen randomized to transperineal re-air with levatorplasty, transperineal re-air without levatorplasty, and transanalectocele repair, symptoms of constipa-ion improved significantly in all groups.owever, similar to transvaginal repair,
t short-term follow-up of 6 months, 12-6% had persistent bowel symptoms,ith the worst outcomes after transanal
epair.18 In a systematic review andmetaanalysis by Maher et al,19 anatomicailure was lower after transvaginal vsransanal rectocele repair. There are fewtudies directly comparing the effect ofhese different approaches on bowelymptoms.
The fact that almost half of women haveersistentbowelsymptomsafterrectocelere-air is likely due to their multifactorial na-ure. Based on radiologic imaging, the pres-nce of incidental small rectoceles has beeneported to be 76% in healthy, nulliparousomen using defecography.20 Even after an
anatomic cure, the function may not im-prove because patients may have underlyingcauses such as dyssynergic defecation, irrita-ble bowel syndrome, symptoms exacerbatedby pharmacologic agents, other neurologicconditions, or even other etiologies of ana-tomic outlet obstruction. Often by the time apatientpresents toaurogynecologist, it isnotpossible to clearly determine which came
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cele.Althoughtherearemanycross-sectionalstudies evaluating the association betweendefecatorysymptomsandrectocele,therearelimited studies assessing the long-term effectof defecatory symptoms on the pelvic floor.
There are limitations to our study. Themajority of our study population pre-sented with vaginal bulge as the primarysymptom and did not undergo extensiveanorectal testing or detailed evaluationof their defecatory symptoms. There-fore, we do not have additional anorectaltesting or imaging for these patients. Wedid not assess bowel habits based onRome III criteria; however, we did assessthe severity of bother using validatedquestions and the frequency of bowelsymptoms. Also, we did not assess painwith defecation, which can also be acommon symptom in women with def-ecatory problems. Finally, we do nothave follow-up beyond 12 months and itis possible that a higher proportion ofwomen may experience recurrent symp-toms beyond this time.
Our study adds to the growing body ofliterature regarding bowel symptoms af-ter rectocele repair that will be helpful indiscussing expectations for women con-sidering surgical treatment. In womenwith primary and/or significant defeca-tory symptoms who have a coexistingrectocele, clinicians should consider fur-ther anorectal testing and conservative man-
TABLE 4Multiple logistic regression for riskfor persistent splinting (n � 63)
VariableUnadj(95%
Graft use 0.73 (0...................................................................................................................
Age 0.97 (0...................................................................................................................
Postoperative rectocele stage 1.02 (0...................................................................................................................
Duration of splinting 1.91 (0...................................................................................................................
Perineal body length 1.71 (0...................................................................................................................
CI, confidence interval; OR, odds ratio.
Sung. Bowel symptoms after rectocele repair. Am J Obstet
agement including education, counseling,
and behavioral therapies prior to proceedingto surgery.21 Women electing surgical repairof rectocele who have significant defecatorysymptoms should be counseled appropri-ately regarding expected outcomes if theirprimary goal is to improve these defecatorysymptoms. f
REFERENCES1. Raza-Khan F, Cunkelman J, Lowenstein L,Shott S, Kenton K. Prevalence of bowel symp-toms in women with pelvic floor disorders. IntUrogynecol J;21:933-8.2. Morgan DM, DeLancey JO, Guire KE, FennerDE. Symptoms of anal incontinence and difficultdefecation among women with prolapse and amatched control cohort. Am J Obstet Gynecol2007;197:509.e1-6.3. Saks EK, Harvie HS, Asfaw TS, Arya LA. Clin-ical significance of obstructive defecatorysymptoms in women with pelvic organ pro-lapse. Int J Gynaecol Obstet 2010;111:237-40.4. Ellerkmann RM, Cundiff GW, Melick CF, Ni-hira MA, Leffler K, Bent AE. Correlation of symp-toms with location and severity of pelvic organprolapse. Am J Obstet Gynecol 2001;185:1332-8.5. Arya LA, Novi JM, Shaunik A, Morgan MA,Bradley CS. Pelvic organ prolapse, constipa-tion, and dietary fiber intake in women: a case-control study. Am J Obstet Gynecol 2005;192:1687-91.6. Bradley CS, Nygaard IE, Brown MB, et al.Bowel symptoms in women 1 year after sacro-colpopexy. Am J Obstet Gynecol 2007;197:642.e1-8.7. Bradley CS, Brown MB, Cundiff GW, et al.Bowel symptoms in women planning surgeryfor pelvic organ prolapse. Am J Obstet Gynecol
ctors
d OR, Adjusted OR,(95% CI)
–2.35) 0.49 (0.13–1.86)..................................................................................................................
–1.03) 0.97 (0.91–1.04)..................................................................................................................
–2.36) 0.97 (0.40–2.37)..................................................................................................................
–4.02) 2.25 (1.02–4.93)..................................................................................................................
–3.46) 1.87 (0.88–3.94)..................................................................................................................
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