INTRODUCTION
Lower urinary tract symptoms (LUTS) are classified into storage, voiding, and postmicturition symptoms (a feeling of incomplete emptying following urination and/or postmicturition leakage) [
1]. The feeling of incomplete emptying adopted by the International Continence Society is defined as the subjective sensation or complaint that the bladder does not feel empty at the end of micturition [
2]. The feeling of incomplete emptying is seen frequently in both men and women, usually alongside other voiding, storage, or postmicturition LUTS. The feeling of incomplete emptying does not always correlate with the finding of significant residual urine, as it can be felt even with an empty bladder [
3].
Symptoms associated with female voiding dysfunction are commonly associated with postmicturition symptoms and women may experience concomitant stress and urge incontinence [
4]. Among the postmicturition symptoms in women, the feeling of incomplete voiding is reported to be more common than postvoid dribbling [
5]. It is reported that 8.5% of women have had the experience of the feeling of incomplete emptying. The prevalence is known to increase at the age of 40 years and remains at a steady level of 10% in older individuals. Overall, several studies have focused on voiding or storage symptoms, whereas the feeling of incomplete voiding has received relatively little attention [
6,
7].
Uroflowmwtry (UFM) and postvoid residual (PVR) volume are recommended as indispensable first-line objective screening tools [
4]. In a previous study analyzing conventional parameters, including voided volume, maximum flow rate (Qmax), and PVR volume, these factors were not associated with the feeling of incomplete emptying in men [
8]. Therefore, the present study utilized voiding time, time to Qmax, average flow rate, and flow time in addition to conventional parameters in the analysis of the manifestation of a feeling of incomplete emptying in women. In addition, a 24-hour voiding diary was assessed to analyze the patients’ voiding pattern. The primary endpoint of this study was to identify the factors reflecting the feeling of incomplete bladder emptying in women, which may be utilized to develop novel treatment strategies.
MATERIALS AND METHODS
Patient Cohort
Medical records were obtained from a prospectively maintained database for female patients without a history of treatment for LUTS between January 2014 and December 2018 at a single outpatient clinic. This cohort was developed to improve the clinical and epidemiological understanding of symptom profiles. The patients’ clinicopathologic data, including age, body mass index, LUTS symptoms, UFM, PVR volume, voiding diary, and medical history were obtained. To investigate the chief complaints for visiting our urological outpatient clinic, we provided questionnaires, comprising International Prostate Symptom Score and overactive bladder symptom score (OABSS), to promote the understanding of the components of LUTS. Additionally, the feeling of incomplete emptying, which was assessed according to a score (0, not at all; 1, less than 1 in times; 2, less than half the time; 3, about half the time; 4, more than half the time; 5, almost always), was categorized into 2 groups: a score of 0 or 3 as non-severe and a score 4 or 5 as severe [
8]. Quality of life was assessed according to a score (0, delighted; 1, pleased; 2, mostly satisfied; 3, mixed; 4, mostly dissatisfied; 5, unhappy; 6, terrible).
The OABSS comprised 4 questions regarding daytime frequency, nocturia, urgency, and urge incontinence. The diagnosis of overactive bladder (OAB) was defined as OABSS ≥3 with an urgency score of ≥2. Using 24-hour voiding diaries, we reviewed the number of voids per day and night, the minimum and maximum volumes of voids, and the shortest and longest voiding intervals. PVR volume was measured using a bladder scanner (BioSon-500, MCube Tech, Seoul, Korea). Uroflowmetric measurements were performed using Bluetooth UFM (Cube flow_S, MCube Tech, Seoul, Korea). The objective parameters including voided volume (VV), voiding time, average flow rate, Qmax, time to Qmax, and flow time were retrieved from the UFM data.
The detailed medical history of 353 patients was reviewed, and patients with uncontrolled diabetes mellitus, urinary tract infection, urolithiasis, bladder carcinoma, and history of using medications such as hormonal supplements, antipsychotics, or anticholinergics that could affect LUTS, and those who had undergone lower abdominal surgery were excluded (n=11). Patients with a PVR volume >20 mL or the ratio of PVR volume to total volume (TV: sum of VV and PVR volume) >10% were also excluded (n=131).
Good Clinical Practice Protocols
The study was carried out in agreement with applicable laws and regulations, good clinical practices, and ethical principles as described in the Declaration of Helsinki. The Institutional Review Board of Gangnam Severance Hospital approved this study protocol (approval number: Gangnam Severance Hospital 2019-0467-001). This study was performed with the use of the methodological index for nonrandomized studies. The requirement for informed consent from the patients before study participation was waived.
Statistical Analyses
All of the values were expressed as number (%) or mean±standard deviation. Between patient groups, the parameters were compared using Student t-test. Simple and multiple linear regression analyses were used to identify the independent parameters associated with the feeling of incomplete emptying or quality of life. Univariable and multivariable analyses were performed to predict the group with severe symptoms. Receiver operating characteristic (ROC) curves and area under the ROC curves were used to obtain the cutoff value. These optimal cutoff values were based on predefined values and according to a sensitivity analysis using Youden index (sensitivity+specificity –1). All reported P-values are 2-sided, and a P-value of ≤0.05 was considered to indicate statistical significance. All statistical tests were carried out with IBM SPSS Statistics ver. 25.0 (IBM Co., Armonk, NY, USA).
DISCUSSION
Urologists and general practitioners encounter women with LUTS who complain of the feeling of incomplete emptying despite no or little PVR volume in the clinical setting. PVR volume in several urodynamic studies was not useful for the assessment of the feeling of incomplete emptying [
9-
11]. Furthermore, VV and Qmax in UFM as first-line screening parameters were not correlated with the feeling of incomplete emptying in men [
8]. Therefore, to date, the feeling of incomplete emptying has only been regarded as a subjective symptom. For the precise explanation of this symptom, we additionally introduced time-dependent parameters as obtained by UFM. Of note, time to Qmax was identified as a predictive factor for patients with severe symptoms. Moreover, we reviewed 24-hour voiding diary data to analyze voiding patterns. Smaller minimum volume of voids was associated with an increase in the severity of feeling of incomplete emptying in patients with OAB.
There are several presumptions that explain the mechanisms underlying the feeling of incomplete emptying in women. First, time-dependent parameters obtained by UFM indicated time to Qmax as a significant factor in patients with severe symptoms. The delay in time to Qmax may have affected the patients’ feeling of incomplete emptying regardless of Qmax itself. Second, a smaller minimum volume of voids was associated with increased severity of feeling of incomplete emptying in patients with OAB. Decreased Qmax owing to a small-voided volume, in turn, may have provoked the feeling of incomplete emptying. Such factors assessed by uroflowmetric measurements may indicate multifactorial etiologies underlying the feeling of incomplete bladder emptying in women with little PVR. In addition, experience of small-voided volume may have provoked the feeling of PVR. Therefore, these 2 factors, independently or in combination, may have affected the deterioration of the feeling of incomplete emptying and quality of life.
Urologists and general practitioners have questioned why some patients have the feeling of incomplete emptying. Several explanations for the development of such symptoms have been suggested. First, the feeling of incomplete emptying with little PVR volume may be associated with the sensory changes in the bladder. Afferent activity is derived from some degree of volume, tension, and nociceptive receptors in the bladder and urethra [
12]. The bladders of OAB patients appear to be more sensitive than those of non-OAB patients [
13-
15]. In an analysis of voiding behaviors in OAB patients, the degree of urgency sensation was increased in OAB patients compared to that in normal subjects at any given bladder volume, and this was not dependent on the urgency episodes [
14]. Van Brummen et al. [
13] showed that patients with OAB symptoms had lower micturition and bladder volumes than those without the symptoms. Therefore, a hypersensitive bladder can explain why some patients have the feeling of incomplete emptying concomitant with OAB disorder. Second, regarding female sex, pregnancy and parturition might have a delayed effect on the development of the feeling of incomplete emptying. The voiding problems associated with urinary urgency and voiding difficulties in women may be more likely to worsen among those who have had multiple vaginal deliveries due to repeated injury to the muscles, nerves, and connective tissue of the pelvic floor [
16]. In rats with multiple pregnancies and parturition, the bladder showed hypertrophy, instabilities, increased voiding pressure, and residual volume [
17]. The modified bladder function leads to a dysfunction similar to that induced by obstruction, which increases the sensitivity to adrenergic and cholinergic stimulations compared to that in controls. This assumption supports the findings of Maserejian et al. [
5], who reported that the prevalence of postmicturition symptoms increased at the age of 40 years in women.
Our results showed that the etiology of the feeling of incomplete emptying may arise from both voiding and storage mechanisms. The feeling of incomplete emptying was significantly associated with worsening of both voiding and storage symptoms in men, which was consistent with previously reported results [
8]. The present work is the first study to identify that total OABSS and daytime frequency were higher and nocturia and urge incontinence were more frequent among women with severe symptoms, whereas urgency in the OABSS subdomain scores had no association with severe symptoms. However, the feeling of incomplete emptying seemed to not be associated with OAB. The proportion of OAB diagnosis was not different between the non-severe and severe groups. Generally, women with bladder oversensitivity exhibit a bladder capacity of <250 mL [
18]. In this study, there were no differences in the bladder capacities according to the severity of the feeling of incomplete emptying. Therefore, our data suggest that the feeling of incomplete emptying is not related to OAB or bladder oversensitivity, but instead can be regarded as a separate category.
Women who report the feeling of incomplete emptying among the LUTS subtypes have been reported to be most bothered by their health issues [
5,
19,
20]. In our study, the feeling of incomplete emptying was significantly correlated with decreased quality of life, which is comparable to previously published findings. An experimental study in rats with multiple pregnancies and parturition reported that bladder dysfunction showed an increasing sensitivity to adrenergic and cholinergic stimulations [
17]. The feeling of incomplete bladder emptying occurs immediately after micturition; thus, it may be postulated that specific neurotransmitters and their receptors would be associated with the symptoms. Physicians are frequently faced with the dilemma of prescribing alpha-blockers or anticholinergics in patients with the feeling of incomplete emptying as its pathophysiology remains unclear. Despite this unclear rationale, our findings would thus be useful in developing novel treatment strategies.
Despite the several strengths, the present study was inherently limited by its small size and retrospective nature. Moreover, although the clinical factors associated with the feeling of incomplete bladder emptying in women were identified, urodynamic studies to measure bladder function are required for precise diagnosis. Furthermore, the criterion used to stratify the severity of feeling of incomplete emptying was arbitrary; thus, it warrants validation in future studies. Finally, although the menopausal status and vaginal birth delivery were associated with the significant factors of female voiding symptoms, we did not check the hormonal therapy history of the patients in our database. Future studies are warranted to elucidate the basic mechanism of incomplete voiding sensation and to design trials to improve the symptoms and quality of life in women with the feeling of incomplete emptying.
In conclusion, women with the feeling of incomplete emptying who have insignificant PVR volume following urination exhibit severe voiding dysfunctions and low quality of life. This symptom may be associated with the small minimum volume of voids and longer time to Qmax, and this finding may be utilized to develop novel treatment strategies.