Is there a difference between women with or without detrusor overactivity complaining of symptoms of overactive bladder?

Authors


Correspondence: Ilias Giarenis, Department of Urogynaecology, King's College Hospital, Denmark Hill, London SE5 9RS, UK.

e-mail: ilias.giarenis@nhs.net

Abstract

What's known on the subject? and What does the study add?

  • Overactive bladder syndrome (OAB) is a highly prevalent medical condition, which is linked to the urodynamic observation of detrusor overactivity (DO). Urodynamics detect DO in about half of female patients with OAB.
  • Our study detects significant differences between female patients with OAB with and without DO. DO could be considered as a more severe form in the wide OAB spectrum and the two terms should not be used interchangeably. The detected differences should be taken into account in the design of studies for the assessment of new selective or combination treatments of OAB and in the provision of treatment in everyday clinical practice.

Objective

  • To determine if there are differences between female patients complaining of symptoms of overactive bladder (OAB) with and without detrusor overactivity (DO).

Patients and Methods

  • The present study was a cross-sectional study of consecutive women attending a one-stop urodynamic assessment clinic with OAB symptoms.
  • The King's Health Questionnaire (KHQ) and a 3-day bladder diary incorporating the Patient's Perception of Intensity of Urgency Scale (PPIUS) were used to assess symptoms and health-related quality of life (HRQoL).
  • The participants underwent multichannel urodynamics (UDS) according to the International Continence Society (ICS) recommendations.
  • Patients whose symptom of urgency was not reproduced during the laboratory test underwent a 4-h ambulatory UDS test.

Results

  • Of the 556 patients who were included in the study, 43% were diagnosed with DO by either laboratory (227/556) or ambulatory UDS (11/39).
  • There was no difference between the groups in age, body mass index (BMI), menopausal status or the presence of prolapse.
  • Patients with DO had a smaller functional bladder capacity (P < 0.001), higher urgency episode frequency (P < 0.001) and larger maximum and mean urge ratings (P < 0.001).
  • No significant differences were found in daytime or nocturnal micturitions between the groups.
  • The presence of DO had a more negative impact on the quality of life, with a statistically significant difference between the groups in six of the domains of the KHQ.

Conclusions

  • The present study detects objective and subjective differences between female patients with OAB with and without DO.
  • Women with DO experience more significant impairment to their quality of life and have a greater degree of bladder dysfunction.
Abbreviations
BMI

body mass index

DO

detrusor overactivity

HRQoL

health-related quality of life

KHQ

King's Health Questionnaire

OAB

overactive bladder syndrome

POPQ

pelvic organ prolapse quantification

PPIUS

Patient's Perception of Intensity of Urgency Scale

UDS

urodynamics

Introduction

Overactive bladder syndrome (OAB) is a highly prevalent medical condition that is estimated to affect 10.7% of the worldwide population (455 million people) [1]. It is defined by the ICS and the International Urogynecological Association (IUGA) as urgency with or without urgency urinary incontinence, usually accompanied by daytime frequency and nocturia, in the absence of UTI or other obvious pathology [2]. This condition impairs the health-related quality of life (HRQoL) [3] of affected individuals and is associated with a substantial economic burden [4].

Traditionally, OAB has been related to the urodynamic observation of detrusor overactivity (DO), characterized by the occurrence of involuntary detrusor contractions during filling cystometry, which can be spontaneous or provoked [2]. A previous study of patients with symptoms of OAB has shown that 69% of men and only 44% of women had DO [5]. However, a more sensitive investigation such as ambulatory urodynamics (UDS) can detect DO in up to 70% of female patients with OAB [6]. Other urodynamic diagnoses related to OAB, such as sensory urgency, bladder oversensitivity and low compliance [2], are vaguely defined and inconsistently used in the literature and everyday clinical practice.

The association between OAB and DO is not very clear. Some believe that DO is simply missed by laboratory UDS, as ambulatory UDS have a much higher sensitivity for detecting DO [6]. The limited studies comparing bladder diaries, symptoms and urodynamic variables between female OAB patients with and without DO have shown contradictory results. Haylen et al. [7] concluded that both groups had the same spectrum of bladder dysfunction. However, others have shown that patients with DO had smaller maximum voided volumes per void, more incontinence episodes [8] and were more likely to complain of urgency incontinence than those without DO [9]. A study with a large sample size comparing bladder diaries incorporating validated urgency scales and disease-specific HRQoL questionnaires could further explore the association between OAB and DO.

The purpose of the study was to determine if there are objective and subjective differences between female patients with OAB with and without DO.

Materials and Methods

This was a cross-sectional study in a tertiary referral Urogynaecology Unit. Consecutive women attending a one-stop urodynamic assessment clinic with OAB symptoms between January 2011 and April 2012 were included in the study. Ethical approval was granted by the South Central—Oxford C Research Ethics Committee.

We excluded women who were unable to read and complete a questionnaire in the English language; who were <18 years old; who had dementia or memory disorders; who had known neurological conditions such as stroke, multiple sclerosis, spinal cord injury or Parkinson's disease; who were on antimuscarinic medication within 7 days of attendance at the clinic; or who had evidence of UTI on urine analysis (presence of nitrites with or without leucocytes) on the day of the appointment.

All women were asked to complete a disease-specific HRQoL questionnaire (King's Health Questionnaire [KHQ]) [3] and a 3-day bladder diary incorporating the validated Patient's Perception of Intensity of Urgency Scale (PPIUS) [10], before attending the urodynamic clinic. The five grades of the PPIUS (from 0 [no urgency], to 4 [urgency incontinence]) were used to assess the degree of urgency associated with each void. Urgency episodes were counted as suggested by Cardozo et al. [11] as voids with PPIUS level 3 and 4 (without or with urgency incontinence, respectively). Daytime urinary frequency, nocturnal frequency and the functional bladder capacity were recorded from the bladder diary. The symptom domain of the KHQ was used to assess the presence of lower urinary tract symptoms. The nine HRQoL domains of the KHQ were scored on a 0 (best) to 100 (worst) scale.

Initial assessment included medical history, physical examination and urine analysis. Pelvic organ prolapse was assessed in both the lithotomy position and standing with the patient exerting a maximal Valsalva manoeuvre using the pelvic organ prolapse quantification (POPQ) system [12]. The partcipants then underwent multichannel UDS according to the ICS recommendations [13], using a Laborie Aquarius Triton machine. The operators, three clinical fellows and two specialist nurses from our department, were competent in performing UDS according to national standards [14], having performed at least 100 of them before the beginning of the study.

Filling cystometry was performed in the supine position at a rate of 100 mL/min. Filling was stopped either when the patient developed a strong desire to void or when 500 mL of fluid had been infused into the bladder, whichever occurred first. The patient was then moved to the standing position and provocative manoeuvres (coughing, running water and hand-washing) were performed.

Patients whose symptom of urgency was not reproduced during the laboratory test underwent a 4-h ambulatory UDS test with the MMS Luna ambulatory recorder, following a standardized protocol [15]. Where there was uncertainty regarding the diagnosis, patients were reviewed in our weekly multidisciplinary meeting with the participation of four consultants, three clinical fellows, two specialist nurses and one pelvic floor physiotherapist. The final diagnosis used in the present study was based on the conclusion of the multidisciplinary meeting.

Normally distributed continuous variables were presented as means and SDs and compared using an unpaired, two-tailed Student's t-test. Non-normally distributed continuous and ordinal data were expressed as medians and ranges, and differences were evaluated with the Mann–Whitney U-test. Categorical variables were reported as frequencies using percentages and compared using the Pearson chi-squared test. P < 0.05 was considered to indicate statistical significance. Statistical analyses were performed using SPSS (V17, Chicago, IL, USA).

Results

A total of 702 consecutive female patients with OAB were screened, and 556 patients fulfilling the inclusion criteria were included in the study (Fig. 1). The mean (sd) age was 52.1 (14.8) years, the mean (sd) BMI was 28.1 (6.0) and 53% of them were postmenopausal. In all, 39 (7%) patients underwent an ambulatory test, as the symptom of urgency was not reproduced during laboratory UDS; 43% of the patients were diagnosed with DO by either laboratory (227/556) or ambulatory UDS (11/39).

Figure 1.

Summary of the patient cohort.

Baseline characteristics are presented in Table 1. There was no difference between the groups in age, BMI, menopausal status and presence of prolapse (POPQ ordinal stage).

Table 1. Baseline characteristics and presence of prolapse in women with and without DO. Data are n (%) unless noted otherwise.
 DO (N = 238)No DO (N = 318)P valuea
  1. aUnpaired t-test for normally distributed continuous variables, Mann–Whitney test for ordinal data and chi-squared test for categorical variables.
  2. Bold figures refer to statistically significant differences (P < 0.05).
Mean (sd) age, years51.79 (16.19)52.39 (13.59)0.602
Mean (sd) BMI, kg/m228.75 (6.30)27.71 (5.77)0.052
Postmenopausal131 (55.0)157 (49.4)0.141
Previous hysterectomy47 (19.7)95 (29.8)0.011
Previous prolapse surgery22 (9.2)51 (16.0)0.006
Previous continence surgery20 (8.4)50 (15.7)0.004
Median (range) ordinal POPQStage 1 (0–4)Stage 1 (0–4)0.308

Patients without DO were more likely to have had previous hysterectomy (P = 0.011), prolapse surgery (P = 0.006) and continence surgery (P = 0.004).

Regarding the bladder diary variables, patients with DO had a smaller functional bladder capacity (median of 370 vs 500 mL, P < 0.001). They also experienced higher urgency episode frequency (P < 0.001) and larger maximum and mean urge ratings (P < 0.001). However, there was no difference in daytime and nocturnal frequency between the groups (Table 2).

Table 2. Bladder diary variables in women with and without DO (N = 391). Data are presented as median (range).
Bladder diary variablesDO (N = 158)No DO (N = 233)P valuea
  1. aMann–Whitney U-test for non-normally distributed continuous and ordinal data.
  2. Bold figures refer to statistically significant differences (P < 0.05).
Daytime micturitions, no./24 h8 (5–17)8 (4–14)0.944
Nocturnal micturitions, no./24 h1 (0–3)1 (0–6)0.131
Functional capacity, mL370 (90–650)500 (100–1100)<0.001
Maximum urge rating4 (2–4)3 (1–4)<0.001
Mean urge rating2.49 (1–4)1.86 (0–4)<0.001
Urgency episodes, no./24 h4.67 (0–13)1.33 (0–14)<0.001

The presence of DO had a more negative impact on quality of life. There was a statistically significant difference between the groups in six of the domains of the KHQ (incontinence impact, role limitations, social limitations, emotions, sleep/energy and severity measures) (Fig. 2). The scores of the different domains of the KHQ are summarized in Table 3.

Figure 2.

Comparison between female patients with and without DO in relation to the domains of the KHQ. GHP, general health perception; II, incontinence impact; RL, role limitations; PL, physical limitations; SL, social limitations; PR, personal relationships; E, emotions; SE, sleep/energy; SM, severity measures.

Table 3. KHQ domains in female patients with and without DO. Data are presented as median (range).
KHQ domainsDO (N = 238)No DO (N = 318)P valuea
  1. aMann–Whitney U-test for ordinal data. GHP, general health perception; II, incontinence impact; RL, role limitations; PL, physical limitations; SL, social limitations; PR, personal relationships; E, emotions; SE, sleep/energy; SM, severity measures.
  2. Bold figures refer to statistically significant differences (P < 0.05).
GHP25 (0–100)25 (0–100)0.281
II100 (33–100)66 (0–100)0.026
RL66 (0–100)33 (0–100)0.046
PL50 (0–100)50 (0–100)0.512
SL33 (0–100)17 (0–100)0.005
PR33 (0–100)33 (0–100)0.592
E66 (22–100)33 (0–100)0.009
SE50 (0–100)33 (0–100)0.038
SM75 (8–100)33 (0–100)<0.001

Urodynamic stress incontinence was demonstrated in 160/318 (50%) patients without DO and 85/176 (48%) patients with DO (P = 0.707). We were not able to assess urodynamic stress incontinence in 62 patients with DO due to the presence of persistent detrusor contractions. Patients diagnosed with DO had a smaller cystometric capacity (median of 400 vs 500 mL, P < 0.001) and lower bladder compliance (53 vs 100 mL/cmH2O, P < 0.001) than the non-DO group.

Discussion

The present study shows clear differences between female patients complaining of OAB with and without DO. To our knowledge, this is the largest study to date comparing characteristics of female patients with OAB and the first one to present a combination of objective, validated subjective and HRQoL data.

The incidence of DO in the present population was 43%. This is similar to that reported by Hashim et al. [5] (44%), who examined a large sample of female patients with OAB. A previous study, using older definitions of OAB and DO, reported a higher DO detection rate (54%) [16]. More recently, DO was identified in only 32% of women with OAB [9]. The routine use of ambulatory UDS has shown a higher rate of DO (70%) in patients with OAB [6], but also the presence of DO in 68% of asymptomatic female volunteers [17], limiting its use as a first-line investigation. As the correlation between OAB and DO has been found to be greater in male patients, with detection rates up to 70% [5], it is of paramount importance that the incidence of DO is quoted separately for each gender to avoid conflicting results in the literature. Several factors have been found to affect the detection of DO, including the filling rate, the patient's position and the nature of the provocative manoeuvres [18]. In our unit, we perform medium-fill cystometry with a filling rate of 100 mL/min and a combination of provocative manoeuvres in women without neurological conditions, as audit of this protocol has revealed it is able to reproduce the presenting complaints in most patients (93% in this sample) without prolonging the test unduly. The performance of ambulatory UDS, when symptoms of urgency were not reproduced, and the multidisciplinary review of cases, where there was uncertainty regarding the diagnosis, added accuracy to the DO detection rate of the present study.

We did not observe a difference in the mean age between women with or without DO (51.8 vs 52.4 years). The results of the present study do not confirm the findings of previous studies, which reported that women with DO were 3–5 years older [7, 9]. The theory that DO is a later form in the natural history of OAB [7] cannot be confirmed by retrospective or prospective cross-sectional studies, but requires well designed longitudinal projects. We hypothesize that the discrepancy between studies is due to the different inclusion and exclusion criteria and the sample size.

To explore further the difference in clinical characteristics between the groups, we decided to include women with pelvic organ prolapse and previous pelvic surgery, in contrast to the studies conducted by Guralnick et al. [8] and Jeong et al. [9]. We limited our exclusion criteria so as to produce more clinically relevant results, as most women presenting to a urogynaecology clinic report a combination of lower urinary tract symptoms and have varying degrees of prolapse. The extent of prolapse, as assessed by POPQ ordinal stage, was not associated with the detection of DO. However, previous hysterectomy, prolapse surgery and continence surgery were more likely in the group without DO. Whilst previous pelvic surgery has been identified as a risk factor for OAB symptoms [19], we could not find any robust evidence in the literature for the relationship between pelvic surgery and DO. Based on our findings, we can postulate that postoperative formation of scar tissue and localized denervation could induce the irritative symptoms of urinary urgency, without inducing the pathophysiological mechanism of DO.

Regarding the bladder diary variables, daytime and nocturnal frequency did not differ between the groups. The results of the present study confirm the results of previous studies [8, 9] and reflect the behavioural modification of fluid intake and voiding in patients with OAB in a move to cope with the sensation of urgency. However, female patients with DO were found to have a smaller functional capacity (median volume of 370 vs 500 mL), a variable less sensitive to behavioural modification, unless those with OAB undergo structured bladder retraining. Despite the clinically significant difference, previous attempts to use the functional capacity as a simple surrogate screening test for DO have shown poor discrimination [20].

Although increased daytime frequency and nocturia contribute to the bother caused by OAB, it is generally understood that urgency drives the other OAB symptoms either directly or indirectly [21]. By using a validated and reliable urgency scale (PPIUS), we have shown that women with DO experience more urinary urgency, measured by mean and maximum urge ratings as well as urgency episode frequency. The results of the present study concur with the findings of Chung et al. [22], who found an association between urgency severity and DO in a mixed-gender population with OAB by using just the maximum urge rating of the urgency severity scale.

As OAB is known to affect the quality of life of those with it, HRQoL data play a central role in the overall assessment. In the present study, female patients with DO experienced a more significant impairment of their quality of life. We consider this statistically significant difference in the six domains as clinically important, as it exceeds the five points considered by Kelleher et al. [23] as clinically relevant. As there is no difference in the general health perception domain of the KHQ, we can hypothesize that the measured statistically significant differences in the six domains are not confounded by other variables affecting the HRQoL. The lack of difference in the domains of physical limitations and personal relationships could be explained by the various individual adjusting strategies adopted by the patients with OAB to cope with their symptoms.

Whilst the present study shows clear differences between our study groups, there is little in the literature regarding the role of DO in the clinical management outcome of OAB. Three studies have shown that patients with and without DO respond equally well to oxybutynin [24], tolterodine [25] and fesoterodine [26]. Additionally, the clinical outcome after sacral neuromodulation has not been shown to be influenced by the presence of DO before the implantation [27]. However, these results are not surprising for treatments that target both the muscarinic receptors of the detrusor muscle and the afferent (sensory) part of the micturition reflex [28]. On the other hand, combination treatment with antimuscarinic agents and vaginal oestrogens improves efficacy in postmenopausal women with OAB [29], but not in women with DO [30]. Whilst most women complaining of symptoms of OAB can be managed on the basis of their symptoms, those with refractory or complex symptoms could benefit from urodynamic examination. As we lack evidence about the pathophysiological mechanisms and natural history of OAB and DO [31], and the current evidence provides us with only short-term results in a ‘trial environment’, the appropriate application of UDS in the evaluation and management of OAB remains controversial.

We acknowledge that our study had some limitations, the first being the accuracy of data recorded by the patients in the bladder diary and PPIUS. Although compliance with diary-keeping was about 70% (391/556), this is typical of clinical practice and the results of the present study can be used in clinical management, where outcome might be different to clinical trials. Another limitation of the study is that we do not present the clinical outcome after treatment in this cohort of patients. As this was beyond the purpose of this cross-sectional study, we did not record clinical outcome variables. Finally, as this is a single-centre study in a tertiary referral unit, the results cannot be generalized for all OAB women or for centres that perform UDS following different protocols or offering ambulatory UDS as a first-line test.

The results of the present study could be used in choosing variables for developing clinical prediction models of DO. The obvious differences should be considered in the design of studies for the assessment of new selective or combination treatments of OAB and in the provision of treatment in everyday clinical practice. The OAB definition should not discourage researchers from searching for the pathophysiological changes and the background of this under-diagnosed and under-treated condition [32].

In summary, female patients with DO experience a more significant impairment of their quality of life and have a greater degree of bladder dysfunction than those without it. DO could be considered as a more severe form in the wide OAB spectrum. The findings of the present study emphasize the need to separate DO from the pathophysiologically complex syndrome of OAB and suggest that the two terms should not be used interchangeably.

Conflict of Interest

Sushma Srikrishna is a Speaker who receives honorarium for Astellas. Dudley Robinson is a Consultant for Astellas, Ferring and Pfizer. Linda Cardozo is a Consultant for Allergan, Astellas and Pfizer.

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