How Does the Urethra Respond to Bladder Filling in Continent and Incontinent Women?

Abstract

Objective:

To describe mean urethral pressure (MUP) during filling cystometry in continent and incontinent women.

Methods:

Incontinent women were recruited from a urogynecology clinic if they answered “sometimes” or “always” to one of the items on the Medical, Epidemiologic, and Social Aspects of Aging questionnaire. Participants were categorized by MESA scores into stress (SUI) or urgency (UUI) incontinence groups. Continent women were recruited from the community. Multichannel urodynamics were performed using microtip catheters. Urethral pressures profiles were obtained with an empty bladder and at 100cc increments during filling. Data were analyzed in SPSS. Continuous variables were compared with independent t-test or ANOVA, categorical variables with chi-square and multivariable comparisons were made with linear regression.

Results:

86 women (30 continent, 56 incontinent: 37 SUI, 19 UUI) with mean±SD age of 48±15 years and BMI of 31±9 participated. 69% were Caucasian, 43% were postmenopausal, and 80% were parous. Continent women were younger (p<0.001) and had lower BMI (p=0.004). Mean cystometric capacity (MCC) was higher in SUI and continent women than in UUI women (430±142, 448±101 and 332±160, p=0.04). Continent women had higher MUP at baseline when controlling for age, BMI and parity (84±35 cmH20 vs 62±28 cmH20; (aR² = 0.2, p=0.02) compared to incontinent women. During filling, MUPs in continent women were 20-30 cmH20 higher at all bladder volumes than incontinent women. MUP increased significantly between baseline and 300cc in continent (p<0.005) and SUI (P=0.04), but not UUI (p=0.48) women.

Conclusions:

Continent women have greater baseline MUP and greater increases in MUP during bladder filling than incontinent women.

Introduction:

The role of urethral sphincter neuromuscular integrity in maintaining continence is widely accepted. Failure in urethral function is recognized as the primary mechanism responsible for stress urinary incontinence (SUI) (1,2). Consequently, SUI treatments, including incontinence pessaries and surgeries focus on compensating for decreased urethral function. In contrast, urgency incontinence is considered to result from malfunction of the detrusor muscles and the urethra is not implicated in its pathophysiology (3,4).

However, recent clinical data demonstrate significant improvement in urgency and urgency urinary incontinence (UUI) symptoms in women with mixed urinary incontinence after midurethral sling procedures (5). The mechanism by which UUI improves after treatments aimed at urethral function is unclear. Prior studies found evidence of urethral afferent denervation in women with UUI. Women with UUI had higher urethral current perception thresholds (higher stimulus was required to activate urethral afferent nerve fibers) (6) and successful treatment with anticholinergic medication resulted in urethral sensation similar to continent controls (7). Few studies have investigated urethral motor function in women with UUI. Chaliha et al found a rise in urethral pressure during filling in women with SUI, but no increase in urethral pressure in women with detrusor overactivity suggesting the urethra may play an important role in UUI (8).

The guarding reflex is a pathway which increases efferent activity to the striated urethral sphincter during increases in bladder filling resulting in feedback inhibition to prevent detrusor contractions (9,10). Numerous investigators have found pudendal nerve firing increases in response to bladder filling to augment the continence mechanism by increasing urethral resistance (11,12). We hypothesized that the guarding reflex may be impaired in women with both stress and urgency urinary incontinence. Therefore, our objective was to add to the literature on urethral function during bladder filling by describing urethral pressure during filling cystometry in a convenience sample of continent and incontinent women.

Methods:

Following IRB approval, (IRB#107881111704), a convenience sample of participants at a single academic medical center were recruited to undergo urodynamics (UDS) if they answered “sometimes” or “often” on one of the 15 items on the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire (13). A higher MESA score indicates more frequent symptoms and scores range from 0–27 for SUI subscale and 0–18 for UUI subscale. The participants were categorized by MESA scores into SUI or UUI groups by using the MESA urge and stress subscale scores and converting them to an index by dividing each subject’s subscale score by the maximum possible subscale score. Those with higher SUI indices were analyzed as SUI participants and those with greater UUI indices were analyzed as UUI participants. A cohort of continent women were recruited from the community using flyers and web-based advertisements.

Consented research participants completed demographic information and the Urinary Distress Inventory-6 (UDI-6) (14). After voiding, participants underwent catheterized post-void residual urine volume assessment and urine dipstick analysis. We excluded women with a history of neuromuscular disease, prior continence surgery, or coagulaopathy; those with stage III or IV pelvic organ prolapse; those less than 6 months from their most recent vaginal delivery; those taking an anticoagulant mediation; and/or those with an elevated post-void residual urine volume (>150cc) or urine dipstick positive for nitrites or leukocytes.

Urodynamics was performed using a Laborie Dorado urodynamic equipment and included retrograde filling cystometry at a fill rate of 80ml/min and static urethral profilometry. An 8 French microtip catheters (Millar Instruments, Houston, TX) was placed in the vagina to measure abdominal pressure, and an 8 French dual micro-tipped catheter with infusion port was placed with the distal transducer in the bladder and the proximal transducer in the midurethra facing 9 o’clock to measure vesical and urethral pressures, respectively. Urethral pressure profiles were obtained using a profilometer set a withdrawl speed of 1 mm per second. Three separate urethral pressure profiles were obtained at each of the following volumes: at baseline, 100cc, 200cc, 300cc and the patient’s maximum cystometric capacity (MCC). The mean urethral pressure was averaged across all 3 readings at a given volume to get a mean urethral pressure (MUP). The functional urethral length (FUL), area of the continence zone (AUC) and maximum urethral closure pressure (MUCP) at baseline and 300cc were also recorded.

A post-hoc power calculation was performed as this was a secondary analysis of a study on EMG parameters in this population. With 30 women in each arm (continent and incontinent), we had 85% power at an alpha of 0.05 to detect a 20-point difference in the MUP between continent and incontinent groups at 300cc. Data were analyzed in SPSS. Continuous variables were compared with independent t-tests or ANOVA. Categorical variables were compared with chi-square test. Variables significant on univariate analysis were entered into a linear regression model for adjusted comparisons. Comparisons were made at 300cc to account for the lower maximum cystometric capacity (MCC) of UUI participants. Data in the tables are reported as means and standard deviations. Figure 1 demonstrates means with standard errors.

Figure 1.

Visual representation of the rise in mean urethral pressure in continent women during bladder filling. Women with SUI had lower mean urethral pressures across filling while women with UUI could not achieve higher bladder capacities and had a decrease in urethral pressure by the end of bladder filling.

Results:

86 women (30 continent, 56 incontinent: 37 with SUI, and 19 with UUI) were recruited (Table 1). The overall cohort had a mean±SD age of 48±15 years and BMI of 31±9. 69% were white, 43% were postmenopausal, and 80% were vaginally parous. Continent women were younger (38±14 vs 53±12, p<0.001), had lower BMI (28±9 vs 32±8, p=0.004) and were more likely to be premenopausal (p=0.04). As expected with the study design, women with SUI had higher MESA stress subscale scores (19.4±4.7 vs 10±5.1, p=0.01) and lower MESA urge subscale scores (6.2±5.8 vs 13.2±4.4, p=0.001) than women with UUI, however, the UDI-6 subscale scores did not differ between groups (49±21 in SUI and 55±18 in UUI, p=0.3). All 37 women with SUI demonstrated urodynamic stress incontinence (USI), and 18/19 with UUI demonstrated urodynamic DO. Four of the 37 women in the SUI group had DO and 2 of the 19 women in the UUI group had USI. Mean UDI-6 scores in the continent women were 4±8; none of the continent women demonstrated USI and 1 demonstrated DO on UDS.

Table 1.

Baseline demographics

	Continent (n=30)	Incontinent (n=56)	p-value	Continent (n=30)	SUI (n=37)	UUI (n=19)	p-value
Age (Mean±SD)	38±14	53±12	<0.001	38±14	48±9	64±12	<0.001
BMI (Mean ±SD)	28±9	32±8	0.004	28±8	29±7	36±9	<0.001
Vaginal Parity (Median [IQR])	1[0-2]	2[2-3]	0.001	1[0-2]	2[2-3]	3[2-4]	0.02
Hispanic Ethnicity N (%)	4 (13%)	8 (14%)	0.9	4 (13%)	7 (19%)	1 (5%)	0.37
Race N (%)  white  Black	16 (53%) 14 (47%)	46 (82%) 10 (18%)	0.03	16 (53%) 14 (47%)	31 (84%) 6 (16%)	15 (79%) 4 (21%)	0.12
Postmenopausal N (%)	4 (13%)	30 (54%)	0.04	4 (13%)	15 (41%)	15 (79%)	<0.001
Total PFDI score (Mean ±SD)	12±30	60±17	<0.001	12±30	60±16	60±18	<0.001
UDI6 Score (Mean ± SD)	4±8	51±19	<0.001	4±8	49±21	55±18	<0.001
Functional Urethral Length (mm) (Mean ±SD)	18±5	18±19	0.88	18±5	19±22	19±11	0.99
Mean Cystometric Capacity (cc) (Mean ±SD)	448±101	404±151	0.18	448±101	430±142	332±160	0.04
Area of the Continence Zone (Mean ±SD)	1007±544	496±318	<0.001	1007±544	483±340	522±274	<0.001

At baseline (0cc in the bladder), continent women had significantly higher MUP than incontinent women (84±35 cmH20 vs 62±28 cmH20, p=0.03), even when controlling for differences in age, BMI and parity (Adjusted R Square aR² = 0.2, p=0.02). Notably, there was no difference in baseline MUP between SUI and UUI groups (64±28 cmH20 vs 60±28 cmH20, p=0.65). During filling cystometry, urethral pressures in continent women were 20-30 cmH20 higher at all bladder volumes than in incontinent women (Table 2). MCC was higher in SUI and continent women than in UUI women (430±142, 448±101 and 332±160, p=0.04), therefore comparisons were made between baseline and 300cc to include all patients. Urethral pressure increased significantly between baseline and 300cc in continent (p<0.005) and SUI (P=0.04), but not UUI (p=0.48) women (Figure 1). The mean increase in MUP was higher in continent women than in incontinent women when controlling for age, BMI and parity (19±22cmH20 vs 8±43 cm H20, aR² = 0.31, p=0.02) and did not differ between SUI and UUI women (6±21 cmH20 vs 2±30 cmH20, p=0.13). In the 25 participants who could tolerate a bladder volume of 500cc, MUP continued to increase to 113±39cmH20 in continent women vs. 73±19 cm H20 in incontinent women, p=0.004. Likewise, baseline MUCP, MUCP at 300cc and AUC were lower in incontinent women (61±31 vs. 95±41 cmH20, 55±24 vs. 99±39cmH20, and 496±318 vs. 1007±544 cmH20/ml, p<0.001 in all). Notably, FUL was the same between groups (18±19 vs 18±5, p=0.88).

Table 2.

Mean Urethral Pressure

	Continent (mean±SD cmH20)	Incontinent (mean±SD cmH20)	p-value	Continent (mean±SD cmH20)	SUI (mean±SD cmH20)	UUI (mean±SD cmH20)	p-value
Baseline (0cc)	84±35 N=30	62±28 N=56	0.03	84±35 N=30	64±28 N=37	60±28 N=19	0.018
100cc	93±30 N=30	73±35 N=53	0.01	93±30 N=30	75±39 N=36	69±26 N=17	0.037
200cc	99±33 N=30	72±34 N=51	0.01	99±33 N=30	74±36 N=36	69±26 N=15	0.004
300cc	100±31 N=28	71±49 N=41	0.06	100±31 N=28	75±51 N=33	54±30 N=8	0.010
Mean Cystometric Capacity (Mean MCC was 449cc, 430cc and 331cc for Continent, SUI and UUI groups)	99±34 N=30	60±25 N=56	<0.001	99±34 N=30	61±23 N=37	59±35 N=19	<0.001

Discussion:

Our study provides modern urodynamic evidence for the presence of the guarding reflex in continent women. The guarding reflex is commonly described as a progressive involuntary increase in the activity of the striated urethral sphincter as the bladder fills which, in turn, leads to an increase in urethral pressure. Our study demonstrates that continent women have greater increases in urethral pressure during bladder filling than incontinent women and may therefore have a better guarding reflex which prevents them from leaking (15).

Additionally, our study suggests that impaired urethral function likely plays an important role in UUI as well as SUI. The urethra’s inability to respond to bladder filling by increasing urethral pressure may explain the presence of urgency and urgency urinary incontinence in some women. There is evidence of impaired urethral afferent innervation in women with UUI (6), but our data suggest that the efferent innervation may also be affected. The striated urethral sphincter cannot activate and increase MUP in women with UUI. Our findings are consistent with another small study that showed a small increase in urethral pressure with bladder filling in women with SUI, but no increase in women with DO (12). It is possible that these alterations in urethral function in women with UUI/DO may contribute to incontinence symptoms in a subset of women. Further studies should focus on how treatments aimed at improving urethral function may improve urgency symptoms.

The International Continence Society, in 2010, tried to define urethral instability as a rise in urethral pressure by greater than 15cmH20 during bladder filling and prior authors have reported that an increase of greater than 15mmH20 in MUP is associated with UUI (16,17). However, in our sample, we found the opposite association. We found that the urethral pressure increased by an average of 18cmH20 in continent women and that smaller increases were associated with incontinence. This suggests that urethral function plays a role in both SUI and UUI.

The strengths of our study include a well characterized group of women with both SUI and UUI and a control group of continent women. All participants completed standardized assessments with validated symptoms questionnaires and multichannel urodynamic testing. There were important baseline differences between the groups that may impact our findings; however, when we controlled for these differences, our findings did not change.

Reproducibility of urethral pressure profiles can be subject to a variety of factors including intrinsic urethral factors, artifact, pelvic floor muscle contraction, and neuromuscular decline if there is a long delay time between tests (18,19). Time delay between tests would not impact our findings since they were performed over several minutes, and only visually symmetric and consistent profiles were included in the analysis to minimize artifact and pelvic floor muscle contraction. Our aim was to determine changes in urethral function amongst women with and without urinary incontinence, so we were specifically interested in differences/changes in urethral factors or function and how they may be impacted by different urinary symptoms or bladder function. Furthermore, Rahmanou et al performed reproducibility testing 2-weeks apart in a group of stress incontinent women and concluded that although the reproducibility was poor, the limit of agreement was acceptable for some tests; in fact, MUP had the highest reproducibility (20).

In conclusion, continent women have greater baseline MUP and greater increases in MUP during bladder filling than incontinent women, suggesting the urethra may play an important role in both SUI and UUI.