Abstract
Background
The association of pelvic organ prolapse with overactive bladder, other lower urinary tract symptoms (LUTS), and the natural history of those symptoms is not well characterized. Previous cross-sectional studies demonstrated conflicting relationships between prolapse and LUTS.
Objectives
Primary aims were to determine the baseline association between LUTS and prolapse and to assess longitudinal differences in symptoms over 12 months in women with and without prolapse. Secondary aims were to explore associations between LUTS and prolapse treatment. We hypothesized that (1) prolapse is associated with the presence of LUTS, (2) LUTS are stable over time in patients with and without prolapse, and (3) prolapse treatment is associated with LUTS improvement.
Study Design
Women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort Study with adequate 12-month follow-up data were included. Prolapse and LUTS treatment during follow-up was guided by standard of care. Outcome measures included the LUTS Tool total severity score (in addition to overactive bladder, obstructive and stress urinary incontinence subscales) and Urogenital Distress Inventory Short Form (UDI-6). Prolapse (yes/no) was defined primarily when POP-Q points Ba, C or Bp were >0 (beyond the hymen). Mixed effects models with random effects for patient slopes and intercepts were fitted for each LUTS outcome and prolapse predictor, adjusted for other covariates. The study had >90% power to detect differences as small as 0.4 SD for less prevalent group comparisons (e.g., prolapse versus not).
Results
Three hundred seventy-one women were analyzed, including 313 (84%) with no prolapse and 58 (16%) with prolapse. Women with prolapse were older (64.6±8.8 vs. 55.3±14.1 years, p<.001) and more likely to have prolapse surgery (28% vs. 1%, p<.001) and pessary treatment (26% vs. 4%, p<.001) during the study. Average baseline LUTS Tool total severity scores were lower (fewer symptoms) for participants with prolapse compared to those without (38.9±14.0 vs. 43.2±14.0, p=0.036), but there were no differences in average scores between prolapse groups for other scales.
For all urinary outcomes, average scores were significantly lower (improved) at 3- and 12-months compared to baseline (all p<0.05). In mixed effects models, there were no statistically significant interactions between POP measure and visit or time-dependent prolapse treatment groups (p>0.05 for all regression interaction coefficients). The LUTS Tool obstructive severity score had a statistically significant positive association with POP-Q Ba, Bp, and point of maximum vaginal descent (MVD). The LUTS Tool total severity scale had a statistically significant negative association with POP-Q Ba and MVD prolapse. No other associations between prolapse and LUTS were significant (p>0.05 for all regression coefficients). Symptom differences between prolapse groups were small: all regression coefficients (interpretable as additive percent change in each score) were between −5 and 5 (SD of outcomes ranged 14.0 to 32.4).
Conclusions
Among treatment-seeking women with urinary symptoms, obstructive symptoms were positively associated with prolapse, and overall LUTS severity was negatively associated with prolapse. LUTS Tool scores improved over 12 months regardless of prolapse status, including those with treated prolapse, untreated prolapse and without prolapse.
Keywords: Pelvic organ prolapse, overactive bladder, lower urinary tract symptoms, natural history, cohort study, Lower Urinary Tract Dysfunction Research Network (LURN)
Condensation
Obstructive voiding symptoms were associated with the presence of prolapse and all lower urinary tract symptoms improved over 12 months in patients with and without prolapse.
Introduction
The association of pelvic organ prolapse (POP) with overactive bladder (OAB), other lower urinary tract symptoms (LUTS), and the natural history of those symptoms is not well characterized. Results from cross-sectional studies are variable. A review published in 2010 identified four studies that all concluded women with POP had a higher prevalence of OAB symptoms compared to women without POP.1 Another survey-based study from 2011 found POP to be an independent risk factor for symptomatic OAB.2 Similarly, Yuan et al3 found that increasing anterior vaginal wall descent may be related to increasing OAB severity. Conversely, Schimpf et al4 reported that urgency incontinence and voiding dysfunction were not more common in women with stage II or greater POP compared to women with stage 0-I POP. A cross-sectional study of 270 women enrolled in the Women’s Health Initiative (WHI) trial with and without POP, found that obstructive urinary symptoms, but not stress urinary incontinence (SUI) or OAB, were associated with vaginal wall descensus.5
Whether LUTS are associated with POP change over time (particularly in untreated women) is poorly studied to date. Bradley et al6 followed 270 women enrolled in the WHI trial annually with symptom questionnaires and POP-Q exams and found in multivariable longitudinal models that increasing vaginal descent over time was associated with increased painful and obstructive urinary symptoms. Increasing vaginal descent over time was not associated with changes in SUI, urgency incontinence or other OAB symptoms.
Last, several groups have also examined the effect of POP surgery on OAB symptoms. One 2007 study limited to women age 65 or older with stage III-IV POP found a reduction in OAB symptoms following vaginal prolapse surgery.7 Another 2013 study found that women with stage III-IV POP were less likely than women with stage I-II POP to experience improvement in OAB symptoms following POP surgery,8 but a similar study found significant improvement in OAB symptoms following POP surgery and no difference according to baseline severity of POP.9 A systematic review published as part of the Fifth International Collaboration on Incontinence in 2013 determined that bladder overactivity may resolve in 40% undergoing POP surgery and that de novo overactivity occurs in 12%.10
The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) was established in 2012 and completed a 1-year observational cohort study to increase our understanding of LUTS by identifying important subtypes of patients with LUTS.11, 12 Women with POP and LUTS represent a distinct subtype of patients with LUTS who have been well-characterized in this cohort study. To our knowledge, no studies have reported on the natural history of LUTS in women with POP compared to women without POP. This information would contribute additional information toward a better understanding of the association of these common conditions in women.
The primary aims of this analysis, performed in treatment-seeking women with bothersome urinary symptoms, are to (1) determine the baseline association between LUTS and POP and (2) to assess longitudinal differences in LUTS over a 12-month period in women with and without POP. The secondary aim is to explore the association between LUTS and POP treatment. We hypothesized that (1) POP is associated with the presence of LUTS, (2) LUTS are stable over time in patients with and without POP, and (3) POP treatment is associated with improvement in LUTS.
Materials and Methods
The LURN Observational Cohort Study was a National Institutes of Health (NIH)-funded, multicenter study enrolling patients seeking treatments for LUTS at six clinical sites across the United States. Study methods have been previously described.13 Men and women over 18 years of age presenting to a LURN clinician with at least one LUTS as reported on the LUTS Tool14 were enrolled. Patients were not required to be treatment-naive at enrollment. Medical history, self-reported LUTS, physical exam findings (including a POP quantification (POP-Q)15 and pelvic floor muscle strength assessment using the Oxford Scale16) and patient-reported outcomes (PRO) reporting on bowel functioning, psychological health, urologic pain, pelvic floor, and sexual function were collected at the baseline visit. Patient-reported outcomes and treatment history (surgeries, medications, behavioral or physical therapies) were also assessed at 3- and 12-month clinic visits. Participants were treated by their physicians according to standard care practices. A negative urine culture was required prior to inclusion in the study.
The primary outcomes were self-reported LUTS using the LUTS Tool14 and the Urogenital Distress Inventory Short Form (UDI-6).17 The LUTS Tool is a 44-item questionnaire assessing the severity and bother of 22 urinary symptoms (Appendix). An overall LUTS Tool severity score, used to show the total LUTS severity, was calculated as the Euclidean length of all LUTS Tool severity questions and weighted by correlations between baseline LUTS Tool responses to account for redundancy between questions.18 In addition to the LUTS Tool severity score three urinary symptom subscales (OAB, obstructive, SUI) were defined for this analysis (definitions included in Appendix). The overall LUTS Tool severity score and the three subscales were normalized by their maximum value and scaled from 0 to 100 so that the scales can be interpreted on a percentage scale, with 0 being least severe (no symptoms), and 100 being most severe (most severe rating for all 22 symptoms). The UDI-6 assesses symptom bother for six urinary symptoms and ranges from 0 to 100 with higher scores indicating higher levels of urinary symptom bother.17 All questionnaires were completed directly by the patient.
The primary exposure of interest was POP. Each outcome measure was evaluated using six different measures of the POP-Q exam, to assess the impact of overall, anterior-predominant, and posterior-predominant POP.15 Both continuous and dichotomous POP measures were studied; dichotomous POP definitions identified POP as present if the POP-Q point of interest descended beyond the hymen (>0) because this “cut-point” for POP is most consistently associated with vaginal bulge symptoms.19 The six measures were (1) maximum vaginal descent (MVD; greatest value of Ba, C or Bp) dichotomous (POP if MVD >0), (2) MVD continuous, (3) Ba dichotomous (POP if Ba >0), (4) Ba continuous, (5) Bp dichotomous (POP if Bp >0), and (6) Bp continuous. The first definition of POP (MVD >0) was used as the primary definition for prolapse (versus no prolapse) throughout the study.
The POP-Q exam was performed by the enrolling physician. POP-Q data for the cohort was independently examined by two investigators (JTK and CSB) using a priori established quality rules. Inconsistent or implausible POP-Q data points were flagged by each reviewer. The two reviewers met to review all flagged data and adjudicate whether the subject should be included. If both reviewers could not come to agreement, the participant was reviewed by all clinicians participating in this study to arrive at a final decision.
Unadjusted comparisons of demographics and clinical characteristics for dichotomous MVD groups were made using chi-square and Wilcoxon rank sum tests. Mixed effect models with random effects for patient slopes and intercepts were used to determine associations between each LUTS outcome and POP predictor of interest. The best subsets method was used to determine which of the following covariates were associated with each outcome and included in each final model as fixed effect predictors: age, race, ethnicity, body mass index, the functional comorbidity index (FCI), smoking status, diabetes, hysterectomy, postvoid residual, and LUTS treatment. Specific treatments assessed as potential covariates were prolapse surgery, placement of a sling, pessary, pelvic floor physical therapy, Kegel exercises, OAB medication, neuromodulation, and onabotulinumtoxinA injection. Time-dependent prolapse treatment groups were also created for the 3- and 12-month visits. Participants who received a pessary or had prolapse surgery between their baseline and 3-month visits were grouped as treated for prolapse at their 3 and 12-month visits, and otherwise grouped as untreated for the 3-month visit. Participants were grouped similarly at the 12-month visit. Interactions between visits and the exposure of interest were explored to assess temporal differences in associations between the outcomes and predictors. Interactions between the exposure of interest and time-dependent prolapse treatment groups were also tested to assess the moderating effect of prolapse treatment used throughout the study on the associations between outcomes and predictors. The study was designed to achieve >90% statistical power to detect differences as small as 0.4 standard deviations in the continuous outcomes (LUTS PRO scores) for less prevalent group comparisons such as those with prolapse versus not.13 All analyses were performed using SAS software, version 9.4 (SAS Institute Inc., 2013, Cary NC). Statistical significance was defined as p<0.05.
Results
Of the 545 female participants enrolled in the LURN Observational Cohort Study, 371 had complete POP-Q data following a quality control review (Figure 1). The excluded participants were similar to included participants in all characteristics except body mass index, prevalence of diabetes and function comorbidity index were all slightly higher in those who were excluded (data not shown). Among the 371 included females, 313 (84%) had no prolapse (i.e., MVD ≤0) and 58 (16%) had prolapse (MVD >0). Participant characteristics (overall and for those with and without prolapse) are presented in Table 1. Participants with prolapse were older than those without prolapse (64.6±8.8 years vs. 55.3±14.1 years, p<.001), were more likely to be White than non-White (93% vs. 79%, p=0.021), and were more likely to be married or in a civil union than not married or in a civil union (74% vs. 55%, p=0.010). Participants with prolapse had more prolapse surgery prior to the study (24% vs. 2%, p<.001) and during the study (28% vs. 1%, p<.001), more pessary use during the study (26% vs. 4%, p<.001) and a higher postvoid residual (60.4±68.3 mL vs. 38.3±45.0 mL, p=.008) at study initiation. Compared to those without prolapse, participants with prolapse had higher average POP-Q Ba (1.1 vs. −2.0 cm, p<0.001), POP-Q C (−2.8 vs. −6.9 cm, p<0.001), POP-Q GH (3.6 vs. 2.7 cm, p<0.001), POP-Q Bp (−0.3 vs. −2.3 cm, p<0.001), and POP-Q D (−5.2 vs. −8.4 cm, p<0.001) measurements. POP-Q metrics are presented in Supplemental Table 1 for all participants and in Supplemental Figure 1 by prolapse group.
Figure 1.
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) diagram showing participant flow for this analysis. Flow chart begins in topmost rectangle with total female participants consented, shows reasons number of participants excluded due to quality control checks and missing data, and ends with the analyzable sample used in the bottommost rectangle. LURN, Symptoms of Lower Urinary Tract Dysfunction Research Network; QC, quality control; POP-Q, Pelvic Organ Prolapse Quantification.
Table 1.
Participant baseline demographics and clinical characteristics (Total and by prolapse group; all participants with non-missing POP-Q overall stage and Ba, Bp, C, and D measurements, n=371). The maximal vaginal descent (MVD) was used to group participants as having no prolapse (MVD≤0, not beyond the hymen) or prolapse (MVD>0, beyond the hymen)*
| Participant Characteristic | Total (n=371) | No Prolapse (MVD ≤0, n=313) | Prolapse (POP MVD >0, n=58) | p-value |
|---|---|---|---|---|
|
| ||||
| Age | 56.8 (13.8) | 55.3 (14.1) | 64.6 (8.8) | <.001 |
| Race | 0.021 | |||
| African-American | 46 (12%) | 45 (14%) | 1 (2%) | |
| White | 301 (81%) | 247 (79%) | 54 (93%) | |
| Multi-racial/other | 24 (6%) | 21 (7%) | 3 (5%) | |
| Hispanic/Latino | 13 (4%) | 9 (3%) | 4 (7%) | 0.183 |
| Marital status | 0.010 | |||
| Married/civil union | 216 (58%) | 173 (55%) | 43 (74%) | |
| Living with a partner | 9 (2%) | 7 (2%) | 2 (3%) | |
| Separated or divorced | 60 (16%) | 50 (16%) | 10 (17%) | |
| Widowed | 26 (7%) | 24 (8%) | 2 (3%) | |
| Single, never married | 59 (16%) | 58 (19%) | 1 (2%) | |
| Education | 0.469 | |||
| Less than HS diploma/GED | 6 (2%) | 6 (2%) | 0 (0%) | |
| HS diploma/GED | 32 (9%) | 28 (9%) | 4 (7%) | |
| Some college or tech school, no degree | 89 (24%) | 71 (23%) | 18 (31%) | |
| Associate’s degree | 43 (12%) | 35 (11%) | 8 (14%) | |
| Bachelor’s degree | 109 (29%) | 97 (31%) | 12 (21%) | |
| Graduate degree Employment status | 88 (24%) | 72 (23%) | 16 (28%) | 0.177 |
| Employed part-time | 53 (14%) | 43 (14%) | 10 (17%) | |
| Employed full-time | 152 (41%) | 136 (43%) | 16 (28%) | |
| Unemployed (looking for work) | 10 (3%) | 9 (3%) | 1 (2%) | |
| Not employed (not looking for work, includes stay-at-home, retired) | 153 (41%) | 122 (39%) | 31 (53%) | |
| Body mass index | 29.9 (7.5) | 30.2 (7.7) | 28.5 (6.3) | 0.126 |
| Body mass index categories | 0.137 | |||
| <25 | 109 (29%) | 90 (29%) | 19 (33%) | |
| 25–<30 | 103 (28%) | 82 (26%) | 21 (36%) | |
| 30–<35 | 82 (22%) | 70 (22%) | 12 (21%) | |
| 35 and over | 76 (20%) | 70 (22%) | 6 (10%) | |
| Current or former smoker (% yes) | 121 (33%) | 101 (33%) | 20 (34%) | 0.702 |
| Diabetes (% yes) | 44 (12%) | 39 (12%) | 5 (9%) | 0.406 |
| Number of pregnancies | 2.7 (4.4) | 2.7 (4.8) | 2.9 (1.5) | 0.033 |
| Number of vaginal deliveries | 1.8 (1.4) | 1.6 (1.4) | 2.5 (1.) | <.001 |
| Hysterectomy (% yes) | 109 (29%) | 94 (30%) | 15 (26%) | 0.522 |
| Previous prolapse surgery (% yes) | 20 (5%) | 6 (2%) | 14 (24%) | <.001 |
| Previous pessary (% yes) | 51 (14%) | 40 (13%) | 11 (19%) | 0.209 |
| Prolapse surgery during study (% yes) | 21 (6%) | 4 (1%) | 17 (29%) | <.001 |
| Pessary during study (% yes) | 30 (8%) | 15 (5%) | 15 (26%) | <.001 |
| Sling placement during study (% yes) | 45 (12%) | 35 (11%) | 10 (17%) | 0.194 |
| Pelvic floor physical therapy during study (% yes) | 125 (34%) | 107 (34%) | 18 (31%) | 0.641 |
| Kegel exercises during study (% yes) | 149 (40%) | 123 (39%) | 26 (45%) | 0.430 |
| Pelvic floor physical therapy or Kegel exercises during study (% yes) | 198 (53%) | 168 (54%) | 30 (52%) | 0.785 |
| OAB medication during study (% yes) | 87 (23%) | 80 (26%) | 7 (12%) | 0.026 |
| Neuromodulation during study (% yes) | 8 (2%) | 8 (3%) | 0 (0%) | 0.218 |
| OnabotulinumtoxinA during study (% yes) | 10 (3%) | 10 (3%) | 0 (0%) | 0.168 |
| None of the above treatments during study (% yes) | 90 (24%) | 82 (26%) | 8 (14%) | 0.043 |
| Functional comorbidity index | 2.3 (2.0) | 2.3 (2.1) | 2.1 (1.4) | 0.988 |
| PVR (mL) | 41.8 (50.0) | 38.3 (45.0) | 60.4 (68.3) | 0.008 |
| Pelvic floor muscle strength (Oxford Scale) | 0.227 | |||
| Grade 0 | 34 (9%) | 28 (9%) | 6 (10%) | |
| Grade 1 | 69 (19%) | 58 (19%) | 11 (19%) | |
| Grade 2 | 75 (20%) | 59 (19%) | 16 (28%) | |
| Grade 3 | 56 (15%) | 48 (15%) | 8 (14%) | |
| Grade 4 | 44 (12%) | 40 (13%) | 4 (7%) | |
| Grade 5 | 18 (5%) | 18 (6%) | 0 (0%) | |
| POP-Q overall stage | <.001 | |||
| Stage 0 | 76 (20%) | 76 (24%) | 0 (0%) | |
| Stage 1 | 125 (34%) | 125 (40%) | 0 (0%) | |
| Stage 2 | 138 (37%) | 112 (36%) | 26 (45%) | |
| Stage 3 | 31 (8%) | 0 (0%) | 31 (53%) | |
| Stage 4 | 1 (0%) | 0 (0%) | 1 (2%) | |
Missingness was 1% or less for all variables except Pelvic floor muscle strength (Oxford Scale, 20% missingness)
POP-Q, Pelvic Organ Prolapse Quantification; HS, high school; GED, General Educational Development Test; OAB, overactive bladder; PVR, postvoid residual.
Distributions of LUTS Tool and UDI-6 scores at each visit by MVD prolapse and prolapse treatment groups are shown in Figure 2. For all scales, average scores were significantly lower (improved) at 3- and 12-month visits compared to the baseline visit (unadjusted for other covariates, all p<0.05), but there was no statistically significant difference between average scores at 3- and 12-month visits (p-value range 0.17–1.0). At baseline, average LUTS Tool total severity scores were lower (fewer symptoms) for participants with POP (MVD >0) compared to those without (38.9±14.0 vs. 43.2±14.0, p=0.036), but there were no differences in average scores between prolapse groups for other scales. There were no differences in average scores between prolapse groups for any of the scales at 3- and 12-month visits.
Figure 2.
Boxplot distributions of LUTS Tool and UDI-6 scales (by prolapse group over time and paneled by scale). Within each box, the horizontal line represents the median and the circle represents the mean. Lines at the bottom and top of each box represent the 25th and 75th percentiles, respectively. The whiskers at the bottom and top of each plot extend to observations closest to 1.5 times the interquartile range (IQR), and dots represent observations outside of this range. Blue boxplots indicate distributions for participants with no prolapse, red boxes indicate participants with prolapse at baseline, green boxes indicate participants with untreated prolapse at follow-up, and brown boxes indicate participants with treated prolapse at follow-up. Prolapse was defined as present if the point of maximum vaginal descent was beyond the hymen based on Pelvic Organ Prolapse Quantification exam. Prolapse treatment included pessary use and/or surgery. LUTS, lower urinary tract symptom; UDI-6, Urogenital Distress Inventory Short Form; OAB, overactive bladder; SUI, stress urinary incontinence; MVD, maximum vaginal descent; POP, pelvic organ prolapse.
Mixed effects model coefficients for each pair of outcome and exposure of interest are presented in Figure 3 and Supplemental Table 2. In every model, there was no statistically significant interaction between the POP measure and visit (p>0.05 for all regression coefficients for interactions between visit and POP measure in any of the performed regressions). There were also no statistically significant interactions between the POP measure and prolapse treatment groups. Therefore, only the average effect across all visits and treatments is presented in tables and figures. For the LUTS Tool obstructive severity score, there was a statistically significant positive association with POP-Q Ba (regression coefficient [95% confidence interval (CI)]=0.85 [0.00, 1.70] per cm increase), POP-Q MVD (regression coefficient [95% CI]=0.98 [0.15,1.81] per cm increase), and POP-Q Bp (regression coefficient [95% CI]=1.13 [0.10, 2.15] per cm increase) measurements. For the LUTS Tool total severity scale, there was a statistically significant negative association with POP-Q Ba prolapse group (regression coefficient [95% CI]=−3.70 [−7.27, −0.14] for Ba prolapse vs. not) and POP-Q MVD prolapse group (regression coefficient [95% CI]=−3.75 [−6.79, −0.72] for MVD prolapse vs. not). No other associations between POP and LUTS were statistically significant (i.e., p>0.05 for all regression coefficients for predictors of interest). While trends were suggested (Figure 3) toward reduced OAB and SUI symptoms in participants with prolapse, particularly anterior-predominant prolapse, these associations did not meet statistical significance. All regression coefficients were between −6 and 5 (standard deviations of outcomes ranged from 14.0 to 32.4). These coefficients can be interpreted as changes on a percent scale as scores were weighted on a scale of 0–100.
Figure 3.
Forest plot of associations between LUTS scores and prolapse predictors, presented as mixed effects model regression coefficients. For each prolapse predictor shown on the right y-axis, the mixed effects model coefficient is shown (i.e., the estimated average change in the LUTS scale score shown on the left y-axis, per unit change or between prolapse groups). LUTS Tool scales were normalized by the maximum value and scaled from 0 (least severe) to 100 (most severe) so that regression coefficients represent additive changes on a percentage scale. In every model, there was no statistically significant interaction between prolapse measure and visit, so the average effect across all visits is presented. The blue horizontal lines represent 95% confidence intervals for each estimate, with any blue horizontal line not crossing the vertical reference line at zero representing statistical significance at the 0.05 level. Prolapse was identified as present for dichotomous definitions if the POP-Q exam vaginal point specified was beyond the hymen. Models included clinical covariates identified using the best subsets method for each outcome from the following: age, body mass index, comorbidity index, smoking status, diabetes, hysterectomy, baseline LUTS scale score, and LUTS treatment. OAB, overactive bladder; POP-Q, Pelvic Organ Prolapse Quantification; MVD, maximum vaginal descent; SUI, stress urinary incontinence; UDI-6, Urogenital Distress Inventory Short Form. *Statistically significant at 0.05 level.
Comment
Principal Findings
In this multicenter prospective cohort study of treatment-seeking women with at least one urinary symptom, prolapse was associated with more severe obstructive LUTS but less severe overall LUTS. Prolapse presence and prolapse severity were not clearly associated with OAB or SUI. LUTS Tool scores improved over 12 months regardless of prolapse status. Similar improvements in LUTS were seen in patients with treated prolapse, untreated prolapse and without prolapse.
Results in the Context of What is Known
Overall, our results demonstrate a potential association between increasing prolapse in all compartments and obstructive LUTS. There is also lower total LUTS Tool severity scores in patients with more anterior vaginal prolapse and overall prolapse, indicating fewer non-obstructive LUTS in patients with prolapse. While symptom differences associated with increasing or decreasing prolapse measures in this study were small, the results were statistically significant after adjusting for other clinical factors and were consistent across several definitions and measures of POP.
We saw no significant relationship between OAB or SUI and POP. However, results suggest a trend toward fewer OAB and SUI symptoms in patients presenting with LUTS who have prolapse, especially when only considering anterior vaginal wall prolapse. These results demonstrate some similarity to a cross-sectional study by Schimpf et al4 evaluating the association between anterior vaginal wall prolapse and LUTS. They found that stage II or greater anterior vaginal wall prolapse was not associated with urgency incontinence or voiding dysfunction but that women without POP were more likely to report SUI. Similarly, in a cross-sectional study of women enrolled in the Women’s Health Initiative, Bradley et al5 found prolapse to be associated with obstructive voiding symptoms but not OAB symptoms.
In contrast, other studies have demonstrated an association between POP and OAB symptoms.1, 20, 21 For example, Digesu et al21 found that urinary urgency and frequency were significantly associated with the presence of prolapse symptoms. However, the population in this study was comprised of women presenting for care in outpatient general gynecology clinics, very different from the population of women seeking care for LUTS in this study. Furthermore, although that study determined women with symptomatic prolapse had more OAB symptoms than community-dwelling women with prolapse symptoms, increasing severity of prolapse was not correlated with those symptoms. The need to strain and the feeling of incomplete emptying were the only urinary symptoms significantly correlated with increasing POP.21
Finding increased obstructive LUTS with increasing POP may make physiologic sense. Post-void residual was significantly higher in the POP group in this cohort, and this is consistent with prior research.21, 22 Obstructive LUTS logically may be associated with decreased ability to completely empty the bladder as the bladder descends inferior to the pubic symphysis. Additionally, this same phenomenon may lead to a concomitant decrease in other LUTS, such as SUI, resulting in lower overall severity scores.23
Clinical Implications
Our findings are most applicable to patients presenting for treatment to tertiary-care urology or urogynecology clinics. In this population, patients with POP may be no more likely to have bothersome LUTS than patients without POP. Patients presenting with LUTS, regardless of the presence of POP, can also be reassured that their symptoms are likely to improve over the course of 3–12 months of follow-up and treatment. The underlying cause for this decrease in symptoms cannot be determined by this study. However, this was a treatment-seeking cohort. Thus, this improvement may be evidence that LUTS treatment is effective. Additionally, at a minimum, this cohort had three visits with a healthcare provider regarding their LUTS over the study period and completed numerous questionnaires about their LUTS. Completing frequent questionnaires may have had a therapeutic benefit. Alternatively, this may represent observational bias.
Research Implications
Given that we saw improvement in LUTS in subjects with and without prolapse, LUTS-specific treatment may be as effective in women with POP as without POP. While some of the improvement in LUTS in the POP group may be attributable to POP surgery or pessary use, this is not certain. Even women meeting our definitions of POP who did not have POP treatment showed improvement in LUTS during follow up. Thus, women seeking treatment specifically for LUTS and not bothersome POP may be as likely to have improvement in their LUTS even if their POP goes untreated. Future research needs to better define (1) which women with POP will have improvement in OAB symptoms and other LUTS with POP treatment, (2) which women with POP will require additional OAB or LUTS treatment even after POP treatment, and (3) which women with POP could realize improvement in OAB or LUTS symptoms without POP treatment.
Strengths and Limitations
The primary strength of this study is that subjects were well characterized with a detailed demographic and medical history, validated questionnaires, and physical exams with POP-Q exams. The POP-Q data underwent careful quality control review prior to analysis. Subjects also come from geographically diverse tertiary-care urology and urogynecology clinics.
Many subjects had to be excluded from this analysis due to inconsistent or missing POP-Q data, and the total number of subjects with clinically significant POP was lower than we had expected. This may have limited our power to find differences between the groups, especially when comparing POP subjects who did or did not have POP treatment. Also, POP-Q measurements were only available at baseline. Prolapse may change over time regardless of whether specific POP treatment occurs, and this may affect LUTS. The study population is predominantly white, which may limit generalizability to other racial/ethnic groups. Finally, there may be selection bias. Subjects with POP may have been primarily seeking care for their POP, rather than their urinary symptoms. Whereas subjects without POP were probably more like to be seeking care for and be bothered by OAB symptoms or other LUTS.
Conclusions
In conclusion, obstructive voiding symptoms and overall LUTS severity were associated with prolapse in a cohort of treatment-seeking women. LUTS scores improved over 12 months in patients regardless of prolapse or prolapse treatment. These results should be considered by clinicians counseling patients about likely outcomes of prolapse treatment.
Supplementary Material
AJOG at a Glance.
A: Why was this study conducted?
The association of pelvic organ prolapse with overactive bladder and other lower urinary tract symptoms (LUTS) and the natural history of those symptoms in treated patients are not well characterized.
B: What are the key findings?
In a multicenter cohort of women with bothersome LUTS, obstructive voiding symptom severity was positively associated with prolapse, while overall LUTS severity was negatively associated with prolapse (at all time-points). LUTS improved at 3- and 12- month follow-up, regardless of prolapse or prolapse treatment (improvement did not differ in patients with treated prolapse, untreated prolapse and no prolapse).
C: What does this study add to what is already known?
Among treatment-seeking women, obstructive voiding symptoms were most clearly associated with prolapse. All LUTS (including overactive bladder and stress urinary incontinence) improve over 12 months regardless of the presence of prolapse or prolapse treatment. These results should be considered by clinicians counseling patients about likely outcomes of prolapse treatment.
Acknowledgements
This is publication number 33 of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).
This study is supported by the National Institute of Diabetes & Digestive & Kidney Diseases through cooperative agreements (grants DK097780, DK097772, DK097779, DK099932, DK100011, DK100017, DK099879).
Research reported in this publication was supported at Northwestern University, in part, by the National Institutes of Health’s National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The following individuals were instrumental in the planning and conduct of this study at each of the participating institutions:
Duke University, Durham, North Carolina (DK097780): PIs: Cindy Amundsen, MD, Eric Jelovsek, MD; Co-Is: Kathryn Flynn, PhD, Jim Hokanson, PhD, Aaron Lentz, MD, David Page, PhD, Nazema Siddiqui, MD, Kevin Weinfurt, PhD, Lisa Wruck, PhD; Study Coordinators: Paige Green, Magaly Guerrero
University of Iowa, Iowa City, IA (DK097772): PIs: Catherine S Bradley, MD, MSCE, Karl Kreder, MD, MBA; Co-Is: Bradley A. Erickson, MD, MS, Daniel Fick, MD, Vince Magnotta, PhD, Philip Polgreen, MD, MPH; Study Coordinators: Sarah Heady, Chelsea Poesch, Shelly Melton, Jean Walshire
Northwestern University, Chicago, IL (DK097779): PIs: James W Griffith, PhD, Kimberly Kenton, MD, MS, Brian Helfand, MD, PhD; Co-Is: Carol Bretschneider, MD, David Cella, PhD, Sarah Collins, MD, Julia Geynisman-Tan, MD, Alex Glaser, MD, Christina Lewicky-Gaupp, MD, Margaret Mueller, MD; Study Coordinators: Sylwia Clarke, Melissa Marquez, Pooja Sharma, Malgorzata Antoniak, Pooja Talaty, Francesca Moroni, Sophia Kallas. Dr. Helfand and Ms. Talaty are at NorthShore University HealthSystem.
University of Michigan Health System, Ann Arbor, MI (DK099932): PI: J Quentin Clemens, MD, FACS, MSCI; Co-Is: John DeLancey, MD, Dee Fenner, MD, Rick Harris, MD, Steve Harte, PhD, Anne P. Cameron, MD, Aruna Sarma, PhD, Giulia Lane, MD; Study Coordinators: Linda Drnek, Marissa Moore, Greg Mowatt, Sarah Richardson, Julia Chilimigras
University of Washington, Seattle Washington (DK100011): PI: Claire Yang, MD; Co-I: Anna Kirby, MD; Study Coordinators: Brenda Vicars, RN, Lauren Daniels
Washington University in St. Louis, St. Louis Missouri (DK100017): PI: H. Henry Lai, MD; Co-Is: Gerald L. Andriole, MD, Joshua Shimony, MD, PhD, Fuhai Li, PhD; Study Coordinators: Linda Black, Vivien Gardner, Patricia Hayden, Diana Wolff, Aleksandra Klim, RN, MHS, CCRC
Arbor Research Collaborative for Health, Data Coordinating Center (DK099879): PI: Robert Merion, MD, FACS; Co-Is: Victor Andreev, PhD, DSc, Brenda Gillespie, PhD, Abigail Smith, PhD; Project Manager: Melissa Fava, MPA, PMP; Clinical Monitor: Melissa Sexton, BA, CCRP; Research Analysts: Margaret Helmuth, MA, Jon Wiseman, MS, Jane Liu, MPH, Sarah Mansfield, MS
National Institute of Diabetes and Digestive and Kidney Diseases, Division of Kidney, Urology, and Hematology, Bethesda, MD: Project Scientist: Ziya Kirkali MD; Project Officer: Christopher Mullins PhD; Project Advisor: Julie Barthold, MD.
Appendix
LUTS Tool Questions & Groupings
How often during the past week did you urinate too frequently?
During a typical day in the past week, how many times did you urinate during waking hours?
During a typical night in the past week, how many times did you wake up because you needed to urinate?
During the past week, how often have you had the feeling your bladder was not empty after urinating?
During the past week, how often have you had a trickle or dribble at the end of your urine flow?
During the past week, how often have you had a sudden need to rush to urinate?
During the past week, how often have you had a delay before you start to urinate?
During the past week, how often did your urine flow start and stop while you were urinating?
During the past week, how often did you strain to urinate or strain while you were urinating?
During the past week, how often have you had a weak urine stream?
During the past week, how often have you had splitting or spraying of your urine stream?
During the past week, how often have you had a sudden need to rush to urinate for fear of leaking urine?
During the past week, how often have you had pain or discomfort in your bladder area?
During the past week, how often have you had a burning feeling when you urinate?
During the past week, how often did you leak urine?
- Below are several situations in which people can leak urine. How often in the past week have you…
- Leaked urine just after you have finished urinating?
- Leaked urine in connection with a sudden need to rush to urinate?
- Leaked urine in connection with laughing, sneezing, or coughing?
- Leaked urine in connection with physical activities, such as exercising or lifting a heavy object?
- Leaked urine when you are sleeping?
- Leaked urine during sexual activity?
- Leaked urine for no reason?
Overactive bladder (OAB) subscale = 1–3, 6, 12, 16b
Obstructive subscale = 4–5, 7–11, 16a
Stress subscale = 16c-d
Overall severity score = 1–15, 16a-g (all 22 severity items)
Footnotes
Conflicts of interest
The authors report no conflict of interest.
Role
The individuals listed in the acknowledgements were instrumental in the planning and conduct of this study at each of the participating institutions as outlined.
Presentations
Pelvic Floor Disorders Week 2021, American Urogynecologic Society, Phoenix, AZ, October 12–15, 2021.
International Continence Society 2021, International Continence Society, Virtual, October 14–17, 2021.
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Contributor Information
Joseph T KOWALSKI, Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA.
Jonathan B WISEMAN, Arbor Research Collaborative for Health, Ann Arbor, MI.
Abigail R SMITH, Arbor Research Collaborative for Health, Ann Arbor, MI.
Margaret E HELMUTH, Arbor Research Collaborative for Health, Ann Arbor, MI.
Anne CAMERON, University of Michigan, Ann Arbor, MI.
John O L DELANCEY, University of Michigan, Ann Arbor, MI.
Whitney K HENDRICKSON, Division of Urogynecology, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT.
J. Eric JELOVSEK, Duke University Medical Center, Durham, NC.
Anna KIRBY, University of Washington Medical Center, Seattle, WA.
Karl KREDER, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA.
H Henry LAI, Division of Urologic Surgery, Departments of Surgery and Anesthesiology, Washington University School of Medicine, St Louis, MO.
Margaret MUELLER, Northwestern University – The Feinberg School of Medicine, Chicago, IL.
Nazema SIDDIQUI, Duke University, Durham, NC.
Catherine S BRADLEY, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA; Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort Study Group.
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