Bladder sensations in male and female overactive bladder patients compared to healthy volunteers: a sensation-related bladder diary evaluation

Abstract

Objectives: To investigate the differences in bladder sensations of overactive bladder (OAB) patients compared to healthy volunteers. In addition, to see if bladder sensations are different in men and women.

Methods: In a prospective, longitudinal study (METC 09-2-095), 66 volunteers and 68 OAB patients were included. Anticholinergic medication was stopped. Subjects filled out a sensation-related bladder diary (SR-BD), for two periods of 3 days, including a 4-points urgency scale and visual analogue scale for perception of bladder fullness.

Results: In total, 6160 voids were assessed. Patients voided more often with higher degrees of urge at a lower mean voided volume (193 vs 270 ml/void; p < 0.001) than healthy volunteers. The mean urinary frequency per litre diuresis was also higher (5.8 vs 4.1/l; p < 0.001) in patients. At the same voided volume: patients perceived a higher mean bladder fullness, independent of the degree of urge, and higher urgency (1.4 vs 0.5/100 ml; p < 0.001) than healthy volunteers. There were no gender differences in the above-mentioned voiding parameters, except for the mean voided volume at urge 3 in volunteers (340 ml in men vs 362 ml in women; p = 0.03) and urge 1 in patients (171 ml in men vs 135 ml in women; p = 0.027).

Conclusions: Bladder sensations were significantly increased in everyday life for both male and female OAB patients compared to healthy volunteers. OAB patients experienced a higher mean bladder fullness sensation, independent of the degree of urge, and higher mean urge/urgency at the same voided volume than volunteers. Bladder sensations are crucial in the assessment of treatment response.

Keywords:

• Urinary bladder
• bladder sensations
• overactive bladder
• urgency
• sensation-related bladder diary

Introduction

The overactive bladder symptom complex (OAB) is defined by the International Continence Society (ICS) as ‘urgency, with or without urge incontinence, usually with frequency and nocturia’, with urgency being defined as: ‘the complaint of a sudden compelling desire to pass urine, which is difficult to defer’ [1]. Overactive bladder is a common condition with an overall prevalence of 11.8%, with similar rates in men and women and an increasing prevalence with age [2]. The prevalence of individuals affected by OAB is expected to increase in the future, due to population growth and ageing of the general population [3]. It is a serious burden for patients and society, with the amount of healthcare costs that it entails [4]. When compared to demographically matched controls, OAB patients report a significantly decreased quality-of-life with higher rates of depressive symptoms, erectile dysfunction, decreased sexual satisfaction and slightly lower levels of overall health [5]. Furthermore, treatment is often unsuccessful as anticholinergic medication achieve cure or improvement in symptoms in only 56% of the cases [6].

In order to achieve successful disease management, we need to know the exact pathophysiology. In the absence of an OAB specific marker, bladder sensations are studied to confirm the clinical diagnosis of OAB, with urgency being the key symptom. Nevertheless, the difference between physiological and pathological bladder sensations is still unclear. Therefore, further research needs to be done to assess the differences between these distinct bladder sensations.

Bladder sensations have been studied mostly with the use of invasive cystometry [7,8]. However, it has been demonstrated that the rate of filling in cystometry or even the use of a catheter gives distorted results [9–11]. Therefore, it has been recommended that evaluation of bladder sensations during daily activities is the most representative [9]. A sensation-related bladder diary (SR-BD) is a non-invasive tool that is used to evaluate these bladder sensations in daily life. Besides urinary frequency and voided volume, these diaries also include the degree of urge and the perception of bladder fullness before each void.

In the past, bladder sensation studies only included female patients because of the uncertainty that the urinary complaints are caused by bladder outlet obstruction rather than OAB. The aim of this study is to find new insights in bladder sensations of OAB patients and healthy volunteers by the use of SR-BDs in both men and women. The hypothesis is that both male and female OAB patients experience enhanced bladder sensations when compared to healthy volunteers and that determination of bladder sensations is possible without the use of invasive cystometry.

Materials and methods

Subjects and sampling

OAB patients and healthy volunteers were included in a prospective, longitudinal study.

Inclusion criteria

Two groups were created. Patients (men and women) older than 18 years were included in the first group, when diagnosed with OAB by their urologist according to the ICS criteria. The second group consisted of subjects who had no history of LUTS and were considered to be healthy volunteers. Possible volunteers were recruited through advertisement. They had to answer several questions about lower urinary tract symptoms (LUTS) taking into account the ICS criteria for OAB [1]. Patients and healthy volunteers had to be well versed in Dutch.

Exclusion criteria

Patients with a post-void residual urine volume (PVR) of >100cc determined by ultrasound and with the presence of a urinary tract infection, determined by urine sticks, were excluded. Volunteers who met the ICS criteria for OAB and/or with current urinary complaints or a urologic history were also barred from the study.

Ethics approval

The study protocol was approved by the local ethics committee (METC 09-2-095).

Protocol

Following enrolment, OAB patients and volunteers were subjected to the same study protocol. At baseline (T = 0) subjects were evaluated, consisting of a medical history check, a dipstick urine check and the measurement of PVR by ultrasound. Anticholinergic medication was stopped 21 days prior to the start of the study (T = 1) to eliminate the effect of the anticholinergics on bladder sensations.

All study subjects filled out sensation-related bladder diaries (SR-BD), internet-based, for two periods of 3 days. The second period of 3 days started 10 days after filling out the first SR-BD. The bladder diaries contained a Visual Analogue Scale (VAS) to draw the perceived bladder fullness sensation, ranging from empty bladder to full bladder and a 4-point scale to grade the perception of urge/urgency [12]. The meaning of the four grades are: 0 = no bladder sensation, 1 = voiding can be delayed for more than 30 minutes, 2 = voiding can be delayed for at least 10 minutes, 3 = need to void now. Grade 3 is considered ‘urge’ in healthy volunteers and ‘urgency’ in patients.

Statistical analysis

A missing value analysis was performed to investigate how much data was missing. Normal distribution of data was demonstrated using a Shapiro-Wilk test with boxplot and a histogram. Depending on the normality of the distributed data, either an independent T-test or Mann-Whitney U-test was used to compare means of frequency, voided volume, void frequency per litre diuresis, functional bladder capacity (FBC), total diuresis and total intake between patients and volunteers. The ‘bladder fullness sensation per volume’ and ‘urge/urgency per volume’ were analysed by dividing each bladder fullness sensation and each urge value by the corresponding volumes voided. Differences in means of number of voids, mean voided volume and mean bladder fullness sensation per volume were assessed for each urge/urgency category too.

A Friedman ANOVA tested if there were any differences in measurements between the urge/urgency categories, for patients and volunteers separately. Additionally, differences in outcomes for means of frequency, voided volume, urge/urgency per volume, void frequency per litre diuresis and FBC, means of frequency, mean voided volume and mean bladder fullness per volume for each urge/urgency category, between men and women, were tested. Analysis was done with either the use of an independent T-test or a Mann-Whitney U-test, depending on the normality of distributions of data, for the group of patients and the group of volunteers separately.

A p-value ≤0.05 was considered as statistically significant. All analyses were performed using SPSS v23 software (IBM SPSS Statistics, Armonk, NY: USA).

Results

Overall, 134 subjects were included; 66 volunteers and 68 patients. All patients completed the first 3 days, one volunteer filled out only 1 day. Both periods of voiding diaries were completed by 59 volunteers and 48 patients. A total of 6160 voids were assessed; 2487 of volunteers and 3673 of patients. Only 0.9% (783 of 81,002 values) of the data was considered to be missing data. Mainly the degree of urge or bladder fullness sensation was not recorded.

There were differences in basic characteristics between patients and volunteers, as the volunteers were younger (48 vs 60 years old) and the volunteer group consisted of more females (35 vs 23 females) compared to the patient group (Table 1).

Table 1. Baseline characteristics of OAB patients and healthy volunteers.

Baseline characteristic	Criterion	Patients (n), n = 68	Volunteers (n), n = 66
Demographic	Male sex	45 (66%)	31 (47%)
	Age (mean ± SD)	60 ± 12	48 ± 15
Use of medication	Antihypertensive drugs	22	5
	Diuretic	4	0
	Alpha-blocker	2	1
	5-alpha reductase inhibitor	1	0
	Anticholinergic drugs	6	0
	Anti-depressant	2	1
	Diabetes medication	8	1
Medical history	Prostate surgery	6	0
	Incontinence surgery	1	0
	Additional urologic history	6	0
	Neurologic history	2	0
	Gynaecologic history	10	2
	Surgical history	21	3

Patients voided significantly more often (10.5 vs 6.7 voids/24 h; p < 0.001) with lower mean volumes per void (193 vs 270 ml; p < 0.001) than healthy volunteers. The mean urinary frequency per litre diuresis was also significantly higher (5.8 vs 4.1 void/l; p < 0.001) in patients. However, the total diuresis (10.4 vs 10 l; p = 0.645) and total intake (11.8 vs 11.6 l; p = 0.840) for the 6 days total, were not significantly different in OAB patients compared to the healthy volunteers. At the same voided volume (100 ml) patients reported an urge/urgency score value with an average of 0.6 for volunteers and 1.3 for patients, on a 4-points urge/urgency scale (p < 0.001). The FBC was ∼100 ml larger in volunteers (548 vs 445 ml in patients; p < 0.001).

Patients significantly voided more often with a higher degree of urgency than volunteers (Figure 1a). However, 28 volunteers voided ∼5.5-times (range = 1–19 voids) at urge 3 (need to void now) over a total of 6 days and 0.4 times daily. Still, this was significantly less often than the patient group (19.7 voids/6 days, p < 0.001 (range = 1–64 voids); 3.6 voids/day, p < 0.001). These 28 volunteers voided at urge 3 with a higher mean voided volume (381 vs 247 ml/void urge 3; p < 0.001) (Figure 1b) and had a lower perception of bladder fullness (31 vs 41%/100 ml urge 3; p < 0.001). The overall mean urinary frequency per litre diuresis was also significantly lower in the volunteers with voids at urge 3 (4.4 vs 5.7 voids/L; p = 0.001) and they had a bigger FBC compared to the patients (531 vs 445 ml; p = 0.025). Nearly all these volunteers had a FBC > 300 ml. One volunteer reported nine voids with urge 3 with a mean frequency of 11 voids a day, a mean voided volume of 178 ml and FBC of 200 ml.

Figure 1. (a) Mean distribution of daily voids and mean voided volume for each degree of urge between patients and volunteers (n = absolute number of participants who experienced this degree of urge); Urge 0: 0.9 vs 0.5 voids/day, p = 0.001; Urge 1: 3.3 vs 2.3 voids/day, p < 0.001; Urge 2: 1.9 vs 4.0 voids/day, p < 0.001; Urge 3: 0.4 vs 3.6 voids/day, p < 0.001. (b) Mean voided volume per urge (number above measurement) mean ± SD. Urge 0: p = 0.010; Urge 1: p < 0.001; Urge 2: p < 0.001; Urge 3: p = 0.001. (c) Mean bladder fullness sensation at 100 ml per degree of urge (number above measurement) mean ± SD. Urge 0: p = 0.069; Urge 1: p = 0.001; Urge 2: p = 0.001; Urge 3: p = 0.008.

Figure 1b shows that patients void with significant lower voided volumes within each degree of urgency compared to healthy volunteers. The higher the degree of urgency, the higher the amount of volume voided. For the same voided volume (100 ml) patients reported a higher bladder fullness sensation compared to volunteers, independent of the degree of urge (Figure 1c). The difference in bladder fullness sensation per 100 ml at urge 0 between patients and volunteers was not significantly different (p = 0.069).

The Friedman ANOVA, which analysed differences between urge/urgency categories, showed a significant difference between urge/urgency categories for mean number of voids (p < 0.001) and mean voided volume (p < 0.001) in both volunteers and patients separately. The bladder fullness sensation per volume showed no significant differences between urge/urgency categories in patients (p = 0.313) nor in volunteers (p = 0.392).

Figure 2 shows the mean bladder fullness perception and mean voided volume at the same degree of urge. Patients seemed to experience the same perception of bladder fullness at each degree of urge compared to the healthy volunteers, however at a lower mean voided volume. Additionally, a positive association between the degree of urge, the voided volume and bladder fullness perception was found.

Figure 2. Mean bladder fullness vs mean voided volume for each degree of urge. The mean bladder fullness for each degree of urge is plotted against the mean voided volume corresponding with the same degree of urge (number above measurement). Urge 0: p = 0.883; Urge 1: p = 0.189; Urge 2: p = 0.064; Urge 3: p = 0.053.

Male patients were compared to female patients and male volunteers to female volunteers. There were no statistical differences between male and female patients or male and female volunteers for means of frequency (10.4 vs 10.8 voids/day; p = 0.542 and 6.5 vs 6.6 voids/day; p = 0.804, respectively), voided volume (196 vs 187 ml/void; p = 0.246 and 261 vs 278 ml/void; p = 0.436, respectively), urge/urgency per volume (1.4 vs 1.3/100 ml; p = 0.990 and 0.7 vs 0.5/100 ml; p = 0.056, respectively), void frequency per litre diuresis (5.5 vs 6.2 voids/l; p = 0.319 and 4.3 vs 4.0 voids/l; p = 0.319) and FBC (437 vs 462 ml; p = 0.692 and 528 vs 565 ml; p = 0.244, respectively).

For each urge/urgency category the means of frequency, mean voided volume and mean bladder fullness per volume were not statistically different between male and female patients or male and female volunteers either, except for the mean voided volume at urge 3 in the volunteer group (340 ml in men vs 362 ml in women; p = 0.03) and at urge 1 in the patient group (171 ml in men vs 135 ml in women; p = 0.027).

Discussion

In this study, we found important differences in bladder sensations between OAB patients and healthy individuals. OAB patients experienced a higher perception of bladder fullness and urgency for the same voided volume when compared to healthy volunteers.

In the past, several studies have tried to study bladder sensations in daily life in the most representative manner. De Wachter and Wyndaele [13] were the first to state that SR-BDs may provide an initial non-invasive tool to study bladder sensations. Later, their comparison of SR-BDs with filling cystometry demonstrated that sensation-related symptoms are more accurately studied by the use of SR-BDs compared to cystometry [14]. Subsequently, the use of a 3-day SR-BD was assessed in the analysis of overactive bladder symptoms in community-dwelling women [15] and to evaluate differences between urinary-incontinent and continent women [16]. Both showed that patients with OAB void with lower volumes and higher urgency compared to healthy volunteers. Heeringa et al. [17] reported a positive correlation between voided volume and the degree of urge/urgency too [16]. There appears to be a large range of bladder volume per degree of urge/urgency, with a substantial overlap in the amount of volume voided among different degrees of urge/urgency [16,18]. Our results are in line with these findings and confirm that OAB patients experience altered bladder sensations. In the current study the voided volume was taken into account explicitly, when studying the differences in bladder sensations. We found that OAB patients experience a higher perception of bladder fullness independently of the voided volume or degree of urgency, which indicates that hypersensitivity for the afferent information from the bladder may play a role in the pathophysiology of OAB. This view has been postulated in other studies [19,20].

The absolute need to void may develop differently between individuals [21,22]. The perception of bladder fullness does not increase linearly and the volume at which the first sensation is perceived is lower in OAB patients with a more rapidly increasing sensation compared to healthy individuals [21,22]. Our results are consistent with these previous results, as shown in Figure 2. However, the perception of bladder fullness and degree of urge have shown to be independently positively correlated to the voided volume, but not to each other, which has not been mentioned before.

There was no statistical difference (p = 0.069) for bladder fullness perception/100 ml at urge 0 between patients and volunteers (Figure 1c). This is expected, since urge 0 at a small voided volume can considered to be a convenience void.

Additionally, evaluation of treatment of OAB can be done non-invasively by the use of these new parameters. Current evaluation of treatment response is based on the improvement of voiding frequency, voided volume and number of incontinence episodes. Including bladder sensations by using SR-BDs might improve treatment evaluation, since urgency is the key symptom of OAB. Normalisation of bladder sensations during treatment could be an extra parameter to determine success. For example, with sacral neuromodulation, this could be useful during test stimulation and might be taken into account in the decision to implant a permanent IPG. Of course, future studies should first validate the use of SR-BDs in the treatment of OAB.

The strength of this study is the large sample size, with the assessment of 6160 voids. SR-BDs were used for a total of 6 days, to evaluate the bladder sensations in daily life in a reliable manner [9,23]. A missing value analysis showed only 0.9% of all data was missing, mainly the degree of urge or bladder fullness sensation, hence statistical imputation was not considered to be useful.

This study distinguishes itself from other bladder sensation studies by the inclusion and evaluation of both men and women, which is more representative for findings in the general population, given the gender prevalence [2]. Men are often excluded as subjects in OAB studies, because the aetiology of the bladder complaints in men can be related to bladder outlet obstruction (e.g. benign prostatic hyperplasia). Therefore, subjects with a PVR of >100 cc were excluded from this study. Additionally, statistical analysis showed no differences in bladders sensations between included men and women.

A limitation of the study is that the mean age of the volunteer group is significantly lower than the patient group’s (p < 0.001), with the possibility of over-estimating the difference in bladder sensations between both groups. This is not surprising, since the prevalence of OAB increases with age [2]. However, a previous study showed that in healthy women bladder sensations diminish with age and increases in subjects with detrusor overactivity [24]. Nevertheless, there are many factors that have an influence on bladder sensations [25,26].

The use of the same urge rating scale in both healthy individuals and OAB patients, with urge 3 (need to void now) being considered to be urgency in patients, can lead to discussion. It has been debated if urgency is a distinct feeling compared to the normal urge or if it is an intensification of the physiological urge [27]. If urgency would be a distinct bladder sensation, a distinct urge scale would be necessary to evaluate bladder sensations in healthy volunteers and OAB patients. Blaivas et al. [28], however, demonstrated in urgency incontinent patients that there are two sensations of urgency described by these patients. One being an intensification of the normal urge to void and the other a different sensation. Moreover, a focus group investigation demonstrated that bladder sensations are experienced in the same way by OAB patients as by healthy volunteers and in both groups there seem to be two types of urgency: a sudden absolute need to void and a slowly developing absolute need to void [22]. The current study shows that even 28 healthy volunteers, who stated not to have any urological symptoms and did not meet the ICS criteria for OAB, experienced urge 3. However less often (0.4 vs 3.6 daily voids) at higher mean voided volumes (381 vs 247 ml/void), lower overall voiding frequencies corrected for intake (4.4 vs 5.7 voids/l, a higher mean FBC (531 vs 445 ml) and a lower perception of bladder fullness (31 vs 41%/100 ml). The one volunteer with a FBC < 300 ml probably did not consider her voiding behaviour as problematic. Moreover, previous studies mentioned asymptomatic women who described voids preceded by severe urgency as well [29], suggesting that patients rather experience an intensification of normal urge. With these results, use of the same urge scale is no limitation. Nevertheless, since healthy volunteers voided with higher volumes at urge 3 compared to patients, the degree of urge needs to be put in perspective with the voided volume.

For the future, an evaluation is needed to test the reproducibility of the study results before using this method for a more representative quantified evaluation of bladder sensations.

In conclusion, significant differences in bladder sensations between OAB patients and healthy volunteers were found. Gender does not seem to play a role in the experience of bladder sensations. In daily life, patients experience a higher perception of bladder fullness (independent of the degree of urge) and urge/urgency for the same voided volume as healthy volunteers. This gives an indication that hypersensitivity of the sensory control of the bladder plays a role in the pathophysiology of OAB. In the future, bladder sensations could be useful in the evaluation of therapy response with the use of SR-BDs.

Acknowledgements

Dr van Koeveringe reports grants and other from Astellas, grants and other from Solace therapeutics, other from Boston Scientific, outside the submitted work.

Disclosure statement

The authors report no conflicts of interest.