Buchsbaum, Gunhilde M. MD1,2; Duecy, Erin E. MD1; Kerr, Lindsey A. MD4; Huang, Li-Shan PhD3; Perevich, MaryAnn BSN1; Guzick, David S. MD, PhD1
One of 10 women in the United States will undergo at least one surgical procedure for repair of pelvic organ prolapse during her lifetime. Close to 30% of these women will require further intervention because of prolapse recurrence.1 Our knowledge of etiology and biologic risk of pelvic organ prolapse is limited. Child birth in general is believed by many to be the major risk factor for pelvic organ prolapse.2–5 However, the majority of parous women never develop symptomatic prolapse, however, and prolapse sometimes occurs in women who have never given birth. Therefore, it is likely that other factors either lead to or protect against the development of pelvic organ prolapse. Body mass index (BMI), increased age, smoking, constipation, and vaginal hysterectomy have been linked to pelvic organ prolapse.6–8 White race is also considered a risk factor for prolapse, while African and Asian ethnicity is thought to be protective5
These considerations raise the question of an underlying inheritable predisposition for pelvic organ prolapse. However, hardly any data are available to date evaluating the familial risk for pelvic organ prolapse. Jack and coworkers9 found the relative risk for prolapse of sisters of women with advanced pelvic organ prolapse to be five times the risk of women in the general population.
We compared the prevalence of prolapse in nulliparous postmenopausal women with the corresponding rates in their biological sisters who have had at least one vaginal delivery to investigate the role of vaginal delivery and familial factors in the development of pelvic organ prolapse.
MATERIALS AND METHODS
The Research Subjects Review Board at the University of Rochester approved this study. We recruited pairs of full biological sisters from the general population in western New York and northern Vermont between February 2002 and November 2004 to participate in this cohort study on urinary incontinence and pelvic organ prolapse in postmenopausal nulliparous women and their parous sisters. Findings on urinary incontinence in 143 sister pairs have been previously reported.10 Presented here are the findings on pelvic organ prolapse in the 101 of these sister pairs who underwent clinical evaluation. Both sisters had to be postmenopausal and willing and able to complete questionnaires and clinical evaluation to be included in this study. One of the sisters had to be nulliparous, while the other sister had to have undergone at least one vaginal delivery. All sister pairs in the study completed a screening questionnaire. The questionnaire had been used in a previous study11 and included sections on demographics; medical, surgical, and obstetric history; and medication use. The questionnaire contained sections asking about the presence of urinary and fecal incontinence, pelvic organ prolapse, and associated symptoms. The questions screening for prolapse and related symptoms were: “Have you noticed anything bulging from your vaginal opening? ” Participants answering “yes” were further questioned “Does this cause any problems emptying your bladder or bowels?” and “Do you need to reduce this bulge with your fingers to empty?”
The sister pairs were invited to undergo a physical examination. Efforts were made to schedule sisters for evaluation on different dates. Written informed consent was obtained from all study subjects before the examination. Study participants received an honorarium of $50.00 for this visit. Examiners were masked to the parity of study subjects and to sibling status. The physical evaluation commenced with a general assessment of mobility and gait. The remainder of the physical examination was performed in the supine or partial recumbent position at a 45-degree angle in a urodynamics chair, which is similar to a birthing chair. The examination included an assessment of pelvic organ relaxation. Participants were asked to perform maximal Valsalva while the measurements of pelvic support were obtained. Measurements were recorded in 1-cm intervals. Pelvic organ prolapse was quantified using the Pelvic Organ Prolapse Quantification staging system approved by the International Continence Society.12 Pelvic and rectovaginal examinations were performed, noting pelvic organs or their absence, palpable pelvic or rectal masses, integrity of anal sphincter, and the tone of anal sphincter.
Prolapse stages by compartment and points of greatest relaxation by Pelvic Organ Prolapse Quantification measurements were compared within sister-pairs. We considered stages 0 and I normal support, and combined these stages in our analysis under “no prolapse.” Stages II, III, and IV were combined under “prolapse.” As prolapse-related symptoms increase abruptly with prolapse progression beyond the hymen, we also analyzed our data by presence of “advanced prolapse” (stages III and IV) and absence of protrusion beyond the hymen (stages 0, I, and II).13
In our comparison of prolapse between the two sisters within a pair, we regarded the degree of prolapse as different if the prolapse observed in one sister was two or more stages apart from that of the other sister. Thus, only differences outside observational variations were considered.14
This study was designed to assess urinary incontinence and pelvic organ prolapse in nulliparous postmenopausal women and their parous sisters. We assumed a prevalence of 60% for pelvic organ prolapse stage II or greater based on prevalence of pelvic organ prolapse observed in Swedish women aged 50 and older15 and determined that 91 sister pairs would provide 80% power to detect a 20% or more difference in the prevalence of pelvic organ prolapse between sisters at the 5% significance level.
Because this is a matched-pair design, the prevalence of pelvic organ prolapse as well as the prevalence of other response variables were compared between parous and nulliparous sisters using the McNemar’s test to account for possible familial correlation. To further investigate familial association, a χ2 test for testing independence was performed to examine the degree of association between the sister pairs. Stepwise logistic analyses were performed on potential risk factors, such as body mass index, age, hysterectomy, prior surgery for correction of pelvic floor dysfunction, and diabetes, for nulliparous and parous women separately. Variables found to be significant at the P=.05 level were entered into a multivariable logistic regression analysis to assess their effect on the likelihood of developing pelvic organ prolapse. Conditional logistic regression was used to identify risk factors in discordant pairs.
One hundred one sister pairs completed the questionnaire and underwent clinical evaluation. There were no differences between the 42 sister pairs that returned the questionnaire only and the ones that also underwent clinical evaluation. Demographic variables of this cohort are depicted in Table 1. Except for parity, there was no statistically significant difference in any of the demographic parameters.
Of the nulliparous and parous women, 83 (82.2%) and 44 (43.6%), respectively, had no pelvic organ prolapse (stages 0 and I). Our findings in the apical, anterior, and posterior compartments in nulliparous and parous women are shown in Table 2.
When comparing findings on pelvic examination between nulliparous women and their parous sisters by compartment, we found a high concordance in prolapse stage among sister pairs. Concordance in prolapse stage among sister pairs was 74.3% in the anterior compartment. This familial association was statistically significant (χ2 P=.05, 95% confidence interval [CI] 0.657–0.855). In the remaining 25.7% of the sister pairs with discordant prolapse stage (prolapse observed in one sister differed by two or more stages from that of the other sister) the parous sister had the more advanced prolapse in all but two of the pairs as detailed in Table 3. Comparing findings on examination of the posterior compartment between sister pairs, we noted a concordance of 75.3% (CI 0.668–0.837). In the discordant sister pairs, it was again the parous sister in 22 (88.0%) of the 25 pairs, who presented with the advanced prolapse stage. Comparing findings in the apical compartment within sister-pairs, we found a 91.1% (CI 0.855–0.967]) concordance in prolapse stage. In all of the 9 discordant sister pairs, the parous sister was observed to have the more advanced prolapse stage.
We further assessed correlation of pelvic support within sister pairs by comparing Pelvic Organ Prolapse Quantification measurements of the most dependent position of the posterior and anterior vaginal wall, the cervix or vaginal cuff, the genital hiatus, perineal body, and the total vaginal length. We found that at least two thirds of sister pairs were concordant within 1 cm at all measured points but the cervix or vaginal cuff. Figure 1 depicts the distribution of Pelvic Organ Prolapse Quantification differences within sister pairs by compartments. When discordance within sister pairs was observed, in 80% of cases, the parous sister had the measurement corresponding to greater pelvic organ descent at all points.
For sister pairs with discordant prolapse status (prolapse observed in one sister, stage II, III, or IV, and none in the other sister, stage 0 or I), vaginal parity was a risk factor for greater pelvic organ descent. Evaluating the risk for prolapse (stages II, III, and IV) by compartment, the parous sister had more than a seven-fold risk for posterior vaginal wall prolapse (odds ratio [OR] 7.750, 95% CI 2.736–21.955, P<.001) and an 11-fold risk for advanced prolapse (stages III and IV) of the anterior vaginal wall (OR 11.333, 95% CI 3.481–36.896, P<.001). Evaluating parity on a continuous scale, the risk for prolapse (stages II, III, and IV) increased with the number of vaginal deliveries. Each vaginal birth increased the risk for posterior wall prolapse more than twice (OR 2.848, 95% CI 1.526–5.312, P=.001), and conferred a more than three fold risk for anterior wall prolapse (OR 3.294, with 95% CI [1.635, 6.636], P=.001).
With regard to other risk factors, we found that body mass index and diabetes were not predictors of pelvic organ prolapse (stages II, III, and IV). Only 18 (17.8%) of parous and 4 (22.2%) of the nulliparous women with prolapse in at least one of the compartments had prior vaginal surgery. Further, of the women with a history of vaginal surgery, 12 (44.4%) women—6 nulliparous and 6 parous—were found to have no pelvic organ prolapse in any compartment. We found a concordance of 80% in the history of vaginal surgery within sister pairs (in 3% both had surgery, and in 77% neither had surgery). Of the 57 parous women with prolapse (stages II, III, and IV) in at least one compartments, 11 (19.3%) had prior vaginal surgery.
Age was not a significant predictor for stages II, III, and IV prolapse for nulliparous women (OR 0.91, 95% CI 0.827–1.002, P=.055).
Overall, the prevalence of any prolapse beyond the hymen (stages III and IV) was 13.9% for parous women and 1.0% for their nulliparous sisters (McNemar’s test, P<.001). Of the 75 women with pelvic organ prolapse to the hymen or beyond, 45 (60.0%) had isolated prolapse in one compartment. Of these 14 nulliparous and 31 parous women, the anterior compartment was involved in 16 (15.8%) parous and 6 (5.9%) nulliparous women and the posterior in 15 (14.9%) parous and 8 (7.9%) nulliparous women. Apical prolapse was not observed in isolation, but always in association with anterior vaginal defects. No apical prolapse was observed in nulliparous women.
The combination of an anterior and a posterior defect was observed in 20 (87.0%) of the 23 women with prolapse in two compartments. The remaining three women had a combination of anterior and apical prolapse. Seven parous women (9.3%) had prolapse involving all three compartments. Only 4 (4.0%) of the 23 women with combination of prolapse were nulliparous.
Interestingly, half of the women with stage III and IV prolapse did not report any symptoms. Of the 15 women with pelvic organ prolapse beyond the hymen, only 7 reported feeling a bulge. None of the 127 women without prolapse (stages 0 and I), and 5 of the 54 (9.26%) women with stage II prolapse complained about feeling a bulge.
It is widely accepted that vaginal parity is the major risk factor for prolapse. This study of nulliparous women and their parous sisters is well suited to test this assumption as well as the hypothesis that familial factors play a role in the development of this condition.9,16
We found that the majority of nulliparous women have no pelvic organ prolapse. We considered women with Pelvic Organ Prolapse Quantification stages 0 and I as having no support defects. Few women, whether parous or not, had symptomatic pelvic organ prolapse.
We compared the prevalence of prolapse observed in our study population stage by stage to that reported in the few studies available for comparison and found them similar. Overall, we found 62.9% of women in our cohort to have stage 0 and I support (82.2% of nulliparous and 43.6% parous sisters), 30.2% stage II support (16.8% nulliparous and 43.6% of parous sisters), 5.0% stage III support (1.0% of nulliparous and 8.9% parous sisters) and 2.0% stage IV support (4.0% of parous sisters). The distribution of pelvic support in women aged more than 60 years reported by Swift 15 and by Nygaard and coworkers6 was similar to the distribution we observed for parous women. Samuelsson and coworkers8 reported their findings in a population of Swedish women with a mean age of 39 years, of which 45.7% were nulliparous. They found an overall prevalence of pelvic organ prolapse of 44% among parous and of 5.8% among nulliparous women.
We did observe a remarkably high concordance in the level of pelvic support among nulliparous women and their parous sisters, suggesting a familial predisposition for this condition. Familial factors have also been postulated to play a role in the etiology of pelvic organ prolapse by Jack and coworkers,9 who found the risk of prolapse of sisters of women younger than 55 years with stage III and IV prolapse to be five times greater than the estimated risk for the general population. The impact of familial factors, conferring either protection from or a risk for pelvic organ prolapse, could explain the observation that the majority of parous women never develop symptomatic prolapse while it does occur in some nulliparous women.
Because our study population consisted of white postmenopausal women, findings cannot necessarily be generalized to younger women or to women of different racial background. Furthermore, we cannot make any assumption about the incidence of prolapse, as we cannot know since what age pelvic prolapse has been present.
In sister pairs with discordant prolapse stages, parous women had the greater degree of prolapse in more than 80% of the cases. Our data confirm previous reports that parity is a risk factor for pelvic organ prolapse.5–8,17 Because all of the parous sisters had at least one vaginal delivery, we specifically addressed vaginal delivery in relation to developing pelvic organ prolapse, thereby avoiding the dilution of the effect if we had used all parous women, including those who delivered only by caesarean. Swift and coworkers17 and Nygaard and coworkers6 found that vaginal delivery did not increase the risk over parity alone. While some authors have found increasing parity to be associated with increased risk for prolapse8,18 others have not.6 We found that an increased number of vaginal deliveries did not confer an overall increased risk for prolapse. However, this did not hold true for discordant sister pairs, where the risk for pelvic organ prolapse increased with each additional vaginal delivery. Thus, while parity clearly does confer a risk for severe prolapse, this overall risk appears to be relatively small.
Besides parity, age has been implicated as a major risk factor for prolapse.5,8,18 Swift and coworkers7 suggested a doubling of the incidence of severe prolapse with every decade of life. Because all our subjects were postmenopausal by design, we can only comment on age as a risk factor in later life. We found age not to be a predictor for advanced prolapse.
Other factors that have been implicated by some to confer increased risk for prolapse are increased body mass index,5 hysterectomy, and prior vaginal surgery.7 We found no association with increased body mass index and prolapse, which concurs with the findings of Swift et al.7 However, both that study and ours might have been underpowered to detect such a difference.
We found the most common site of prolapse to be the anterior vaginal wall and the least common site the apex. Samuelsson and coworkers8 reported similar findings. Hendrix and coworkers5 observed a comparable prevalence of posterior vaginal prolapse but reported twice and three times the prevalence of “some form of” cystocele (32.9%) in parous and in nulliparous women respectively. Interestingly, apical prolapse was not observed among the nulliparous women in our cohort.
As would be expected, the apical prolapse among parous women was not found in isolation, but only in combination with an anterior vaginal prolapse. Combinations of prolapse were rare in nulliparous women. The most common combination by far was that of prolapse of the anterior and posterior vaginal walls. Furthermore, any combination of prolapse included the anterior vaginal wall. Overall, the anterior vaginal wall appears to be the site most susceptible to prolapse.
The most common and consistent complaint of women with prolapse is seeing or feeling a bulge.17 None of the women with stages 0 and I reported prolapse symptoms. This supports the idea that stage I support is a normal finding and should not be considered prolapse. This idea is further supported by the observation that young, nulliparous, asymptomatic women have a wide range of pelvic organ descent.19 Half of the women in our cohort with prolapse beyond the hymen of any compartment reported feeling a bulge. Again, these findings are consistent with those by Swift and coworkers,17 who report an abrupt increase in symptoms with prolapse beyond the hymen. While it is plausible that women should become symptomatic with prolapse protruding beyond the hymen, we cannot explain why many women do not perceive any symptoms with advanced prolapse.
In conclusion, our findings of strong concordance in prolapse stages between nulliparous and parous sister pairs suggest a familial component toward this condition. While parity clearly does confer a risk for severe prolapse, this risk is overall relatively small.
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