The presence of stress urinary incontinence (SUI) or urgency urinary incontinence (UUI) has profound negative impacts on quality of life, exceeding that of other common morbid conditions such as diabetes [
This study is an ancillary analysis employing the databases of two large randomized trials of women presenting for surgical management of SUI: the Trial of Mid-Urethral Slings (TOMUS) study [
We analyzed baseline data from two IRB-approved randomized surgical trials for women undergoing SUI surgery conducted by the Urinary Incontinence Treatment Network (UITN). All participants provided written informed consent. SISTEr randomized 655 women with predominant SUI to either an autologous rectus fascial sling or the Burch colposuspension [
Baseline demographic data included age, self-reported race/ethnicity, and education. Body mass index (BMI, recorded in kg/m2) was calculated from measured height and weight. Specific factors which are related to obstetrical and gynecological history included the number of pregnancies (categorized as 0, 1, 2, and ≥3), menopausal status, hormone replacement therapy, prior hysterectomy, and prior surgery and/or treatment for urinary incontinence or pelvic organ prolapse.
Subjective urinary incontinence symptoms were measured using validated questionnaires: Urogenital Distress Inventory (UDI) [
The UDI measures 3 domains: stress incontinence symptoms, irritative symptoms, and obstructive/discomfort symptoms with bother being measured with a 4-point Likert scale. The scores from each domain are transformed into a continuous scale ranging from 0 to 100, and higher scores indicate greater bother. For the purpose of this analysis, urgency urinary incontinence was defined as present if a subject reported urinary leakage related to the feeling of urgency as “moderate or greatly bothersome” on the UDI. In addition, the irritative domain was used as a measure of a woman’s urge symptoms.
The IIQ consists of 30 items that query the impact of urogenital symptoms on physical functioning, emotional functioning, travel/mobility, and social functioning using a 4-point Likert scale. Each domain is transformed into a scale ranging from 0 to 100 with higher values representing more negative impact.
The MESA questionnaire consists of 15 items total divided into stress and urge subscales. A higher MESA score indicates more frequent symptoms overall (range of 0–45) and for each incontinence subscale (range of 0–27 for SUI and range of 0–18 for UUI).
The following 3 questionnaires were used only in the TOMUS trial. The PGI-S questionnaire asks subjects to describe “how their urinary condition is now” and consists of 4 choices for response: normal, mild, moderate, and severe. The Charlson Comorbidity Index (CCI) encompasses 19 medical conditions weighted from 1 to 6 with total scores ranging from 0 to 37. A CCI of 3-4 is associated with 52% 1-year mortality [
Objective measures included a 24-hour pad test, POP-Q measurements, and bladder volume at the time of a positive stress test.
Analyses were carried out in parallel for the SISTEr and TOMUS subjects as the trials had different inclusion and exclusion criteria representing different populations. Bivariate logistic regression models were fit considering each covariate separately with UUI as the outcome (UUI is defined as present if a subject reported urine leakage related to the feeling of urgency as moderately/greatly bothersome on UDI). Covariates that were statistically and significantly (
Linear regression modeling was used to identify associations with irritative/urgency symptoms reported on the UDI and MESA. A similar, yet independent, technique was used for building the linear regression multivariable models. Specifically, covariates that were statistically and significantly associated with irritative/urgency symptoms were considered in the multivariable models. For continuous explanatory variables, the slope coefficient for the association between a particular independent covariate and UDI irritative subscale/MESA urge symptoms controlling for the other covariates in the model was presented. For categorical covariates, the adjusted mean UDI irritative subscale/MESA urge symptoms controlling for the other covariates in the model was reported for each level of the categorical variable.
All statistical analysis was performed using SAS version 9.2 (SAS Institute, Inc, Cary, NC). A 5% two-sided significance level was used for all statistical testing.
Over two-thirds of women with stress predominant incontinence in both studies reported being moderately or greatly bothered by urine leakage related to the feeling of urgency (UUI in 70% in SISTEr and 68% in TOMUS). This is also reflected in the relatively high mean (standard deviation) UDI-I (47.8 (25.2) in SISTEr and 41.2 (25.4) in TOMUS) and MESA urge scores (6.3 (4.0) in SISTEr and 6.2 (4.0) in TOMUS). The descriptive statistics for the two trials based on the presence or absence of UUI are shown in Table
Descriptive statistics by UUI status and results of separate bivariate logistic regression models with outcome of those having UUI. Results reported separately for the SISTEr and TOMUS trials.
Covariate | SISTEr ( |
TOMUS ( |
||||||
---|---|---|---|---|---|---|---|---|
Yes ( |
No ( |
|
OR |
Yes ( |
No ( |
|
OR | |
Menopausal status/hormone replacement therapy | 0.002 | 0.01 | ||||||
No HRT, Postmenopausal | 178 (39%) | 53 (27%) | 1 | 169 (42%) | 74 (39%) | 1 | ||
Yes HRT, Postmenopausal | 156 (34%) | 67 (34%) | 0.69 (0.46–1.05) | 126 (31%) | 44 (23%) | 1.25 (0.81–1.94) | ||
Premenopausal | 120 (26%) | 76 (39%) | 0.47 (0.31–0.72) | 106 (26%) | 72 (38%) | 0.64 (0.43–0.97) | ||
Prior to UI surgery and/or treatment | 0.01 | 0.19 | ||||||
No | 206 (45%) | 110 (56%) | 165 (41%) | 89 (47%) | ||||
Yes | 249 (55%) | 86 (44%) | 1.55 (1.10–2.17) | 236 (59%) | 101 (53%) | 1.26 (0.89–1.78) | ||
Prior to hysterectomy | 0.09 | 0.03 | ||||||
No | 306 (67%) | 145 (74%) | 276 (69%) | 147 (77%) | ||||
Yes | 149 (33%) | 51 (26%) | 1.38 (0.95–2.01) | 125 (31%) | 43 (23%) | 1.55 (1.04–2.31) | ||
Race/ethnicity | 0.16 | 0.06 | ||||||
Hispanic | 56 (12%) | 15 (8%) | 1.79 (0.98–3.27) | 53 (13%) | 17 (9%) | 1.66 (0.93–2.95) | ||
Non-Hispanic white | 323 (71%) | 155 (79%) | 1 | 307 (76%) | 163 (86%) | 1 | ||
Non-Hispanic black | 34 (7%) | 10 (5%) | 1.63 (0.79–3.39) | 14 (3%) | 3 (2%) | 2.48 (0.70–8.75) | ||
Non-Hispanic other | 41 (9%) | 16 (8%) | 1.23 (0.67–2.26) | 29 (7%) | 7 (4%) | 2.20 (0.94–5.13) | ||
Parity | 0.68 | 0.48 | ||||||
No pregnancies | 16 (5%) | 6 (4%) | 1 | 17 (6%) | 8 (5%) | 1 | ||
One pregnancy | 25 (7%) | 14 (10%) | 0.67 (0.21–2.10) | 37 (12%) | 27 (18%) | 0.64 (0.24–1.71) | ||
Two pregnancies | 112 (33%) | 49 (36%) | 0.86 (0.32–2.32) | 111 (37%) | 51 (34%) | 1.02 (0.42–2.53) | ||
Three or more pregnancies | 185 (55%) | 69 (50%) | 1.01 (0.38–2.67) | 133 (45%) | 65 (43%) | 0.96 (0.39–2.35) | ||
Education | 0.002 | <.0001 | ||||||
48 (11%) | 6 (3%) | 1 | 25 (6%) | 8 (4%) | 1 | |||
High school/GED | 115 (25%) | 56 (29%) | 0.26 (0.10–0.64) | 109 (27%) | 39 (21%) | 0.89 (0.37–2.15) | ||
188 (41%) | 70 (36%) | 0.34 (0.14–0.82) | 160 (40%) | 57 (30%) | 0.90 (0.38–2.11) | |||
BA/BS | 56 (12%) | 42 (21%) | 0.17 (0.07–0.43) | 49 (12%) | 52 (27%) | 0.30 (0.12–0.73) | ||
Grad/Prof | 48 (11%) | 22 (11%) | 0.27 (0.10–0.73) | 60 (15%) | 34 (18%) | 0.56 (0.23–1.39) | ||
Prolapse stage | 1 | 0.34 | ||||||
Stage 0 or 1 | 110 (24%) | 48 (24%) | 1 | 189 (47%) | 77 (41%) | 1 | ||
Stage 2 | 271 (60%) | 116 (59%) | 1.02 (0.68–1.53) | 183 (45%) | 96 (51%) | 0.78 (0.54–1.12) | ||
Stage 3+ | 74 (16%) | 32 (16%) | 1.01 (0.59–1.72) | 31 (8%) | 17 (9%) | 0.74 (0.39–1.42) | ||
UI Severity (PGI-S)* | N/A | 0.001 | ||||||
Normal | 38 (9%) | 23 (12%) | 1 | |||||
Mild | 30 (7%) | 30 (16%) | 0.61 (0.29–1.25) | |||||
Moderate | 202 (50%) | 97 (51%) | 1.26 (0.71–2.23) | |||||
Severe | 132 (33%) | 39 (21%) | 2.05 (1.09–3.84) | |||||
Depression (PHQ-9)* | N/A | 0.0001 | ||||||
<10 | 293 (74%) | 165 (88%) | 1 | |||||
10+ (defined as depression) | 103 (26%) | 22 (12%) | 2.64 (1.60–4.34) | |||||
Charlson Comorbidity Index (CCI)* | N/A | 0.03 | ||||||
0 | 287 (71%) | 153 (81%) | 1 | |||||
1 | 69 (17%) | 27 (14%) | 1.36 (0.84–2.22) | |||||
2+ | 47 (12%) | 10 (5%) | 2.51 (1.23–5.10) | |||||
| ||||||||
Mean (SD) | Mean (SD) | Mean (SD) | Mean (SD) | |||||
| ||||||||
UDI stress score (UDI-S) | 79.8 (20.2) | 73.8 (25.0) | 0.002 | 1.13 (1.05–1.22) | 75.4 (20.6) | 72.5 (23.1) | 0.13 | 1.06 (0.98–1.15) |
MESA stress score | 20.2 (4.1) | 17.2 (5.0) | <0.0001 | 1.15 (1.11–1.20) | 20.0 (4.2) | 17.9 (5.0) | <.0001 | 1.11 (1.06–1.15) |
Age (years) | 52.2 (10.1) | 51.4 (10.8) | 0.37 | 1.08 (0.92–1.27) | 53.6 (10.9) | 51.3 (10.9) | 0.02 | 1.21 (1.03–1.43) |
Body mass index | 30.4 (6.3) | 28.9 (5.4) | 0.003 | 1.05 (1.02–1.08) | 30.7 (7.0) | 29.5 (6.2) | 0.03 | 1.03 (1.00–1.06) |
IIQ total | 190.7 (100.7) | 126.3 (87.7) | <0.0001 | 1.07 (1.05–1.09) | 169.4 (98.2) | 113.4 (83.4) | <.0001 | 1.07 (1.05–1.09) |
Pad weight (g) | 48.6 (87.6) | 31.3 (54.1) | 0.01 | 1.04 (1.01–1.08) | 38.1 (66.9) | 31.5 (66.6) | 0.27 | 1.02 (0.99–1.05) |
Multivariate analyses were carried out using the continuous variables of UDI-I (Table
Final multivariable linear regression models for the SISTEr and TOMUS trials with outcome of UDI-I.
Covariate | SISTEr | TOMUS | ||
---|---|---|---|---|
|
Estimate** |
|
Estimate** | |
Race/ethnicity | 0.001 | 0.18 | ||
Hispanic | 41.30 | 40.46 | ||
Non-Hispanic white | 48.17 | 41.24 | ||
Non-Hispanic black | 55.67 | 47.06 | ||
Non-Hispanic other | 52.65 | 47.80 | ||
Education | 0.006 | <0.0001 | ||
<High school | 56.23 | 46.50 | ||
High school/GED | 50.19 | 50.52 | ||
>High school | 49.04 | 45.27 | ||
BA/BS | 42.90 | 38.20 | ||
Grad/Prof | 48.87 | 40.20 | ||
UI Severity (PGI-S)* | <0.0001 | . | ||
Normal | N/A | 42.11 | ||
Mild | N/A | 35.08 | ||
Moderate | N/A | 45.57 | ||
Severe | N/A | 53.80 | ||
Charlson Comorbidity Index (CCI)* | 0.0003 | |||
0 | N/A | 39.35 | ||
1 | N/A | 42.11 | ||
2+ | N/A | 50.97 | ||
UDI stress score | <0.0001 | 0.17 | 0.06 | 0.08 |
Body mass index | 0.002 | 0.44 | 0.34 | 0.13 |
IIQ total | <0.0001 | 0.11 | <0.0001 | 0.09 |
Pad weight (10 g per unit) | 0.03 | 0.23 | 0.004 | 0. 39 |
**For categorical predictors, least squares means are reported, and for continuous covariates, regression coefficients are reported.
Final multivariable linear regression models for the SISTEr and TOMUS trials with outcome urge symptoms from the MESA scale.
Covariate | SISTEr | TOMUS | ||
---|---|---|---|---|
|
Estimate** |
|
Estimate** | |
Education | <0.0001 | 0.002 | ||
<High school | 8.21 | 7.12 | ||
High school/GED | 6.50 | 7.15 | ||
>High school | 6.52 | 6.65 | ||
BA/BS | 5.34 | 5.62 | ||
Grad/Prof | 6.48 | 5.90 | ||
Depression (PHQ-9)* | N/A | 0.01 | ||
<10 | 6.06 | |||
10+ depression | 6.91 | |||
MESA stress score | <0.0001 | 0.41 | <0.0001 | 0.41 |
Age (10 years per unit) | 0.001 | 0.42 | <0.0001 | 0.54 |
Pad weight (10 g per unit) | 0.001 | 0.05 | 0.0007 | 0.07 |
**For categorical covariates, least squares means are reported, and for continuous covariates, regression coefficients are reported.
Richter et al. demonstrated that higher MESA urge scores were associated with increased odds of failure after SUI surgery [
Urgency urinary incontinence commonly coexists in women undergoing surgery for SUI. More than two-thirds of the 1252 subjects from the SISTEr and TOMUS studies reported “moderately or greatly bothersome” UUI at baseline. We found no modifiable patient characteristics that are associated with the presence of preoperative bothersome UUI in this population of women. However, patients with more comorbidities reported greater bother from LUTS, and higher depression scores were associated with more severe UUI symptoms. Women with UUI reported worse incontinence-related QoL compared to women without UUI, and as bother from irritative LUTS increased, QoL was negatively impacted. Interestingly, similar to the findings of Lowder et al. [
Age and BMI have been the most consistently reported risk factors associated with UUI in large studies of community dwelling women [
Associations between depression and urinary incontinence have been identified in large population-based cross-sectional studies [
The effect of concomitant medical conditions on UUI and LUTS was evaluated using the CCI, and as the CCI score increased, women reported significantly more bother from LUTS. Similar findings were reported by Nuotio et al., who found that older patients with ≥4 chronic diseases had more than 5 times the risk of developing new UUI (CI 2.03–15.54) compared to those with fewer medical conditions [
The strengths of this study were its multicenter design and inclusion of a large population of well-characterized women undergoing SUI surgery. The use of validated instruments and standardized anatomic characterization further strengthens our findings. The main limitation of our analysis is the lack of generalizability to all women with SUI; therefore, our findings cannot be applied to women with urge predominant symptoms or who are not undergoing surgery. However, our study population remains of particular interest given that greater bothersome baseline urgency symptoms have been consistently shown to predict patient dissatisfaction in women undergoing SUI surgery. As over 200,000 women a year undergo SUI surgery in the United States alone [
Although we did not find any baseline patient variables that were associated with UUI in patients undergoing SUI surgery, interesting questions regarding the effect of systemic medical conditions on overactive bladder symptoms were raised and may represent targets for intervention. Why is depression associated with more severe UUI? Does UUI in a patient with depression represent a different pathophysiologic condition than a patient with a more “localized” pelvic floor disorder? Does the association of number and/or severity of chronic diseases with worsening of UUI/LUTS indicate a more systemic problem affecting bladder function that is less likely to resolve after SUI surgery? Clearly, further investigation using a well-characterized population and validated pelvic floor instruments is necessary to clarify the role of depression and concomitant medical conditions in the pathophysiology of UUI and LUTS in women. In addition, greater emphasis on “phenotyping” of our patient populations may shed light on the complex relationship between UUI and SUI and allow clinicians to more accurately predict surgical outcomes.
This work was supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases, U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, and 60401. Support was also provided by the National Institute of Child Health and Human Development and Office of Research on Women’s Health, NIH. Dr. Rickey has grant support from Pfizer. Dr. Hsu is a consultant for AMS. Dr. Mueller is a consultant for and has grant support from Astellas. For the remaining authors, nothing was declared.