Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS.
A wide Medline search was performed including the combination of following words: “LUTS”, “BPH”, “OAB”, “antimuscarinic”, “tolterodine”, “tolterodine ER”. IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER.
Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of α-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment.
Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.
Lower urinary tract symptoms; Overactive bladder; Storage LUTS; Tolterodine; Urge incontinence; Frequency; Nocturia
Bladder desensitization has been investigated as an alternative treatment for refractory detrusor overactivity. Most open and controlled clinical trials conducted with intravesical RTX showed that desensitization delays the appearance of involuntary detrusor contractions during bladder filling and decreases the number of episodes of urgency incontinence.
Urgency is being recognised as the fundamental symptom of overactive bladder (OAB), a symptomatic complex which recent epidemiological studies have shown to affect more than 10% of the Western population. As anti-muscarinic drugs, the first line treatment for OAB, are far from being able to fully control urgency, the opportunity to test other therapeutic approaches is created. The present work was, therefore, designed as an exploratory investigation to evaluate the effect of bladder desensitization on urinary urgency.
Twenty-three OAB patients with refractory urgency entered, after given informed consent, a 30 days run-in period in which medications influencing the bladder function were interrupted. At the end of this period patients filled a seven-day voiding chart where they scored, using a 0–4 scale, the bladder sensations felt before each voiding. Then, patients were instilled with 100 ml of 10% ethanol in saline (vehicle solution) and 30 days later a second seven-day voiding chart was collected. Finally, patients were instilled with 100 ml of 50 nM RTX in 10% ethanol in saline. At 1 and 3 months additional voiding charts were collected.
At the end of the vehicle and 3 months period patients were asked to give their subjective impression about the outcome of the treatment and about the willingness to repeat the previous instillation.
At the end of the run-in period the mean number of episodes of urgency per week was 71 ± 12 (mean ± SEM). After vehicle instillation, the mean number of episodes of urgency was 56 ± 11, but only 4 patients (17%) considered that their urinary condition had improved enough to repeat the treatment. At 1 and 3 months after RTX the number of episodes of urgency decreased to 39 ± 9 (p = 0.002) and 37 ± 6 (p = 0.02), respectively (p indicates statistical differences against vehicle). The percentage of patients with subjective improvement after RTX and willing to repeat the instillation at a later occasion was 69%.
In OAB patients with refractory urgency bladder desensitization should be further investigated as an alternative to the standard management. Additionally, the specific effect of RTX on TRPV1 receptors suggests that urothelium and sub-urothelial C-fibers play an important role to the generation of urgency sensation.
To investigate the association between overactive bladder (OAB) and C-reactive protein (CRP) in a population-based sample of men and women.
SUBJECTS AND METHODS
Epidemiological survey of urological symptoms among men and women aged 30–79 years. A multi-stage stratified cluster design was used to randomly sample 5503 adults from the city of Boston. Analyses were conducted on 1898 men and 1854 women with available CRP levels.
The International Continence Society defines OAB as ‘Urgency with or without urge incontinence, usually with frequency and nocturia.’ OAB was defined as: (1) urgency, (2) urgency with frequency, and (3) urgency with frequency and nocturia.
Odds ratios (OR) and 95% confidence intervals (95% CI) of the CRP and OAB association were estimated using logistic regression.
Prevalence of OAB increased with CRP levels in both men and women.
In men, adjusted ORs (95% CI) per log10(CRP) levels were 1.90 (1.26–2.86) with OAB defined as urgency, 1.65 (1.06–2.58) with OAB defined as urgency and frequency, and 1.92 (1.13–3.28) with OAB defined as urgency, frequency and nocturia.
The association was more modest in women with ORs (95% CI) of 1.53 (1.07–2.18) for OAB as defined urgency, 1.51 (1.02–2.23) for OAB defined as urgency and frequency, and 1.34 (0.85–2.12) for OAB defined as urgency, frequency and nocturia.
Results show a consistent association of increasing CRP levels and OAB among both men and women.
These results support our hypothesis for the role of inflammation in the development of OAB and a possible role for anti-inflammatory agents in its treatment.
C-reactive protein; epidemiology; inflammation; overactive bladder
To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 – 85 years): 11 “cases” with urge incontinence and DO (proven previously) and 10 normal “controls”. Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In “controls”, increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger “cases”, ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly “cases” showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase.
Among normal “controls”, increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent “cases” and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older “cases” reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO).
functional magnetic resonance imaging; aging; urge incontinence; detrusor overactivity; urgency; overactive bladder; insula; anterior cingulate
The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, α1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats.
Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted.
Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment.
Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.
Overactive bladder; Cyclophosphamide; Tamsulosin; Rats
To compare urgency symptoms in women with interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB).
Materials and Methods
Women with diagnoses of IC/BPS (n = 194) and OAB (n = 85) were recruited from the clinical practices of Urologists (n = 8) and Gynecologists (n = 16) with recognized expertise in the diagnosis and management of these conditions. Subjects completed a comprehensive telephone survey about their current symptoms. The questionnaire included 11 questions about urinary urgency. Responses were compared between the two groups.
Urgency was commonly reported as a symptom by women with both conditions (81% IC/BPS and 91% OAB). Compared with IC/BPS, urgency in OAB more often resulted in leakage, and was perceived to be more of a problem. In IC/BPS, the urgency was primarily reported as due to pain, pressure, or discomfort, while in OAB the urgency was more commonly due to fear of leakage. However, approximately 40% of women with OAB also report urgency due to pain, pressure, or discomfort. Similar proportions of both groups (~60%) indicated that the urgency occurred “suddenly” instead of more gradually over a period of minutes or hours.
Urgency symptoms differed in women diagnosed with IC/BPS versus those diagnosed with OAB, but there was significant overlap. This suggests that “urgency” is not a well-defined and commonly understood symptom that can be utilized to clearly discriminate between IC/BPS and OAB. These findings reinforce the clinical observation that it is often challenging to differentiate between these two conditions.
sensations; specificity; symptoms
Accurately measuring urinary urgency is important for diagnosing overactive bladder (OAB) and quantifying improvements in treatment outcome. Various methods have been recommended for evaluating urinary urgency, but these methods assess individual perceptions and preferences. To overcome the subjectivity in measuring urinary urgency, we evaluated the relationship between uroflowmetric parameters and urinary urgency in women with OAB.
Consecutive female patients with lower urinary tract symptoms (n=110) were prospectively enrolled in this study between April 2011 and September 2012. Individuals with a history of using medications that are known to affect bladder function were excluded. All enrolled patients completed uroflowmetry with a delayed time to voiding (T2V). After urination was completed, patients were asked whether they experienced any urinary hesitancy or urgency at that time.
The mean patient age was 56.1 years; 70 out of 110 patients reported some degree of urinary urgency. T2V decreased with increased urgency. Several uroflowmetric parameters were observed to have a significant correlation with urinary urgency. T2V had a meaningful correlation coefficient for individuals with urgency, regardless of the voided volume. There was no significant correlation between the presence of urinary hesitancy and T2V.
We believe that T2V would be a complementary tool for diagnosing and determining the degree of urinary urgency in women with OAB.
Analysis; Women; Overactive urinary bladder; Questionnaire; Urodynamics
The relationship between psychological stress and interstitial cystitis/bladder pain syndrome (IC/BPS) has been well described. Even though there is some overlapping of symptoms between overactive bladder (OAB) and IC/BPS, there have been very few studies that specifically investigated the relationship between psychological stress and urinary symptoms in OAB patients who do not have pelvic pain. Here we examined the relationship between psychological stress levels and the severity of overactive bladder (OAB) symptoms.
Patients diagnosed with OAB (n=51), IC/BPS (n=27), and age-matched healthy controls (n=30) participated in a case control study that inquired about their psychological stress levels using the perceived stress scale (PSS). PSS reported by the three patient groups were compared. Among OAB patients, their responses on the PSS was correlated to OAB symptoms using the following questionnaires: 1) international consultation on incontinence – urinary incontinence (ICIQ-UI), 2) international consultation on incontinence – overactive bladder (ICIQ-OAB), 3) OAB-q short form, 4) urogenital distress inventory (UDI-6), 5) incontinence impact questionnaire (IIQ-7), 6) urgency severity scale (USS), 7) numeric rating scales of urgency symptom, and 8) frequency symptom. Spearman’s correlation tests were performed to examine the relationship between psychological stress levels and the severity of OAB symptoms.
OAB patients reported psychological stress levels that were as high as IC/BPS patients (median 17.0 versus 18.0, p=0.818, Wilcoxon sum rank test), and significantly higher than healthy controls (17.0, versus 7.5, p=0.001). Among OAB patients, there was a positive correlation between perceived stress levels and urinary incontinence symptoms (ICIQ-UI, Spearman’s correlation coefficient=0.39, p=0.007), and impacts on quality of life (UDI-6, IIQ-7, OAB-q quality of life subscale; Spearman’s correlation coefficient=0.32, 0.31, 0.39, and p=0.028, 0.005, 0.029, respectively). No significant correlation was observed between perceived stress levels and urgency or frequency symptoms (ICIQ-OAB, USS, numeric ratings of urgency and frequency).
OAB patients reported psychological stress levels that were as high as IC/BPS patients, and significantly higher than healthy controls. There was a positive correlation between perceived stress levels and urinary incontinence symptoms, and its impacts on quality of life among OAB patients.
Psychological stress; Overactive bladder; Urgency incontinence; Urinary urgency; Interstitial cystitis
To analyze the predictors of therapeutic efficacy after intravesical botulinum toxin A injection for overactive bladder syndrome (OAB) refractory to antimuscarinic therapy.
All consecutively OAB patients, who visited the urologic outpatient clinics of a medical center and refractory to antimuscarinic treatment, were prospectively enrolled. All enrolled patients received intravesical injection of 100 U onabotulinumtoxinA (Botox). The Global Response Assessment (GRA) score ≥ 2 at 3 months after Botox injection was defined as a successful treatment, otherwise failed.
Overall, 89 patients received intravesical injection. Eighty patients, including 42 men and 38 women, had received follow-up at 3 months. The overall success rate was 63.8%. The global response assessment, urgency severity score, urgency, urgency urinary incontinence and frequency episodes, and functional bladder capacity improved after treatment. However, post-void residual volume (PVR) increased, and voiding efficiency (VE) decreased after treatment. Female gender (odds ratio = 3.75) was the only independent factor associated with the success. Female gender (coefficient = 0.74), low baseline overactive bladder symptoms score (coefficient = -0.12) and the presence of OAB-wet (coefficient = 0.79) were independent factors associated with therapeutic efficacy (i.e., GRA score). VE (odds ratio = 0.062) was the only predictor for a large PVR at 3 months. The optimum cutoff value of VE was <87% with the area under the ROC curve being 0.64 (sensitivity = 63.8%, specificity = 57.1%).
The therapeutic effects of Botox can persist till 6 months after treatment. Female gender, low overactive bladder symptoms score and OAB-wet are associated better therapeutic efficacy, and low baseline VE is associated with large PVR. These findings can serve as an initial guide or assist in consultation regarding the treatment of OAB patients with Botox injection.
Bladder wall thickness has been reported to be associated with overactive bladder (OAB) in women. Diabetic women have an increased risk for OAB syndrome and may have an increased risk for bladder wall thickness.
A total of 235 female patients aged 40 to 75 years were categorized into four groups. The first group consisted of women free of urgency or urge urinary incontinence. The second group included nondiabetic women with idiopathic OAB. The third group consisted of women with diabetes and clinical OAB, and women with diabetes but without OAB constituted the fourth group. Bladder wall thickness at the anterior wall was measured by ultrasound by the suprapubic approach with bladder filling over 250 mL.
The diabetic (third group) and nondiabetic (second group) women with OAB had significantly greater bladder wall thickness at the anterior bladder wall than did the controls. However, the difference was not significant between the diabetic (third group) and the nondiabetic (second group) women with OAB. Women with diabetes but without OAB (fourth group) had greater bladder wall thickness than did the controls but this difference was not significant. Additionally, the difference in bladder wall thickness between diabetic women with (third group) and without (fourth group) OAB was not significant.
This is the first study to show that bladder wall thickness is increased in diabetic women with and without OAB. Additionally, nondiabetic women with OAB had increased bladder wall thickness. Further studies may provide additional information for diabetic and nondiabetic women with OAB, in whom the etiopathogenesis of the disease may be similar.
Overactive urinary bladder; Urinary bladder; Diabetes mellitus
To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.
This was a 12-week, open-label, flexible-dose study of adults with OAB (≥ 8 micturitions and ≥ 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject’s and physician’s subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed.
Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p< 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement ≥ 2 points. Significant improvements from baseline (p< 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified.
Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.
Overactive bladder (OAB) is a manifestation of urgency, regardless of urge incontinence, due to involuntary bladder contraction during the storage period. There is a close association between constipation and OAB, but constipation cannot be readily diagnosed. The aims of this study were to evaluate the prevalence of constipation in OAB and the consequent therapeutic effects according to the diagnostic criteria for constipation.
We collected clinical data from 40 children (mean age, 71±22 months) with chief complaints of urgency, frequency, and incontinence. A voiding questionnaire and a 2-day voiding diary were collected, and urinalysis, the Bristol stool scale, and plain abdominal radiography were performed. Constipation was defined as conditions satisfying at least one of the following criteria: Rome III diagnostic criteria, Bristol stool scale types I/II, or a Leech score higher than 8 points as determined by plain radiography. Lower urinary tract symptoms, defecation symptoms, and the bladder volume of patients were examined, and the therapeutic outcomes by constipation diagnostic criteria were evaluated.
Of the 40 OAB patients, 25 had constipation. Among them, 6 had reduced functional bladder capacity (24%; P>0.05). Regarding treatment, in patients who satisfied only one diagnostic criterion, the symptoms improved in 76.9%, 76.9%, and 69.6% of patients meeting the Rome III criteria, Bristol stool scale, and Leech score, respectively (P<0.05). Among the 8 patients satisfying all three criteria, 75% responded to treatment (P<0.05).
The prevalence of constipation in OAB is high. Constipated patients recruited by use of the Rome III criteria, Bristol scale, and Leech score alone and together showed similar outcomes on OAB improvement after the treatment of constipation, which implies that each criterion has the same strength and can be applied comprehensively and generally.
Overactive urinary bladder; Pediatrics; Constipation
An overactive bladder (OAB) may be defined as urgency that is a sudden, compelling, difficult to defer desire to pass urine that is usually accompanied by frequency and nocturia and possibly by incontinence. Obesity and old age are two factors in various causes of OAB. Several epidemiologic studies have identified positive associations among obesity, old age, urinary incontinence, and OAB. However, although exercise has been known to improve obesity and reduce incontinent urine loss, little research has been done in elderly women. Therefore, we investigated the effects of exercise on obesity-related metabolic factors, blood lipid factors, and OAB symptoms in elderly Korean women.
Twenty-one women aged between 69 and 72 years were recruited from the Seoul senior towers in Korea. All subjects worked out on a motorized treadmill and stationary cycle for 40 minutes, respectively, and performed resistance exercise for 30 minutes once a day for 52 weeks. Body composition, blood pressure, blood lipids, OAB symptom score, and King's health questionnaire were investigated and analyzed.
Before performing physical exercise, all subjects showed increased OAB symptoms in association with enhanced body mass index (BMI), percentage fat, and blood lipid profiles. However, physical exercise for 52 weeks suppressed BMI, percentage fat, and blood lipid profiles and thus improved OAB symptoms.
We suggest that long-term physical exercise can be a valuable tool for remarkable improvement of OAB.
Overactive urinary bladder; Obesity; Exercise; Overactive bladder symptom score; King's health questionnaire
(1) To describe the prevalence of childhood and recent trauma in patients with overactive bladder (OAB), and (2) assess the impact of traumatic events on the clinical presentation and the severity of OAB symptoms, quality of life, and psychosocial health.
Patients diagnosed with OAB (n=51) and age-matched healthy controls (n=30) were administered the Childhood Traumatic Events Scale and Recent Traumatic Events Scale, assessing exposure and perceived impact of common traumatic events. Among OAB patients, validated instruments were administered to correlate traumatic exposure to evaluate adult urinary symptoms (ICIQ-UI, ICIQ-OAB, OAB-q, UDI-6, IIQ-7, USS), mood dysregulation (HADS), sleep and fatigue (PROMIS), and psychological stress (PSS).
Childhood sexual trauma was more prevalent in patients with OAB compared to controls (29.4% vs. 6.7%, p=0.041). OAB patients also rated their childhood sexual exposure as more traumatic compared to controls (mean ratings of 1.7 vs. 0.4, p=0.050). There was no difference in childhood deaths (p=0.24), parental upheaval (p=0.87), violence (p=0.099), illness/injury (p=0.683), or any recent traumatic events between OAB and control subjects.
Childhood trauma predicted worse bladder pain (p=0.005), worse non-urologic pain (p=0.017), poorer mood (p=0.001), higher anxiety (p=0.029), higher physical symptom burden (p<0.001), and higher psychological stress (p<0.039). However, childhood trauma did not correlate with the severity of OAB symptoms (urgency, frequency, incontinence).
30% of OAB patients reported childhood sexual trauma. These patients report more pain symptoms, poorer mood, and greater somatic burden. These data highlight the potentiating role of psychosocial stressors from childhood in the adult suffering from OAB.
Overactive bladder (OAB) syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urge urinary incontinence, in the absence of urinary tract infection or other obvious pathology. At present, the pathogenesis of OAB is little known. The number and activity of involved receptors as well as changed relationship between ion channels and receptors were the researched focuses, which increased the excitability and contractility, but reduced the relaxation and coordination of bladder smooth muscle. As we known, Ca2+ as an important second messenger, can be directly involved in the excitation contraction coupling of smooth muscle cell. Especially that, the Ca2+ influx, which is mediated by transmembrane calcium channel, is the most important factor of produced action potentials in excitable cells. TRPC6 as a kind of transmembrane calcium channel, has very close relationship with the smooth muscle cells of respiratory, digestive and circulatory system. Based on these reports and the results of preliminary study, we speculated that Ca2+ influx, and excitement of bladder smooth muscle cells, is mediated by over expression of TRPC6. This may be one factor of produced OAB.
We established the OAB rat model, and characterized the localization of TRPC6 with immunohistochemistry and immunofluorescence detection, as well as the protein and mRNA expression levels of TRPC6 were examined with western blot and RT-PCR detection. Using FK506, the specific inhibitors of TRPC6, we down-regulated the expression of TRPC6, and then characterized the changes of contractile function in bladder smooth muscle of OAB rats with muscle contraction test. After treatment with PDGF in BMSCs, we tested the protein expression of TRPC6 with western blot, and the expression of JNK and P38.
The immunohistochemistry and immunofluorescence of bladder smooth muscles of OAB rats were shown. The positive staining of TRPC6 appeared at cell membrane of bladder smooth muscle. The western blot and RT-PCR results indicated that, the expression of TRPC6 protein and mRNA in OAB was significantly higher than the normal. After administration of FK506, the expression and mRNA of TRPC6 decreased obviously, and there were improved contraction of smooth muscle in OAB rats. TRPC6 protein could be elevated after induction of PDGF in BMSCs. And blockade with the inhibitors of JNK and P38, the protein levels of TRPC6 were decreased.
The expression of TRPC6 protein and mRNA in bladder smooth muscle of OAB was significantly higher than normal. Reduced the expression of TRPC6 can improve bladder function and contraction of smooth muscle in OAB. PDGF could induced TRPC6 expression in BMSCs. P38 and JNK were involved in the regulation of TRPC6 expression in BMSCs.
Pathogenesis; overactive bladder (OAB); TRPC6
Overactive bladder (OAB) is subtyped into OAB-wet and OAB-dry, based on the presence or absence, respectively, of urgency incontinence. In order to better understand patient and physician perspectives on symptoms among women with OAB-wet and OAB-dry, we conducted patient focus groups and interviews with experts in urinary incontinence.
Materials and Methods
Five focus groups totaling 33 patients with OAB symptoms, including three groups of OAB-wet and 2 groups of OAB-dry patients, were conducted. Topics addressed patients’ perceptions of OAB symptoms, treatments, and outcomes. Twelve expert interviews were then conducted in which experts were asked to describe their views on OAB-wet and OAB-dry. Focus groups and expert interviews were transcribed verbatim. Qualitative data analysis was performed using Grounded Theory methodology, as described by Charmaz.
During the focus groups sessions, women screened as OAB-dry shared the knowledge that they would probably leak if no toilet is available. This knowledge was based on a history of leakage episodes in the past. Those few patients with no history of leakage had a clinical picture more consistent with painful bladder syndrome than OAB. Physician expert interviews revealed the belief that many patients labeled as OAB–dry may actually be mild OAB-wet.
Qualitative data from focus groups and interviews with experts suggest that a spectrum exists between very mild OAB-wet and severe OAB-wet. Scientific investigations are needed to determine if urgency without fear of leakage constitutes a unique clinical entity.
focus groups; qualitative research; urge urinary incontinence; grounded theory; overactive bladder
To evaluate the impact of overactive bladder (OAB) on quality of life (QOL), resource use and productivity loss in patients recruited from six hospitals in Korea.
This cross-sectional survey recruited 625 OAB patients between July to December 2013. Patients were categorised into four groups based on the average number of urinary incontinence (UI) episodes over the past three days (0, 1, 2–3 and ≥4 UI/day). QOL was measured using the Incontinence-Specific Quality of Life Instrument (I-QOL), the Overactive Bladder Questionnaire (OAB-q), and a generic health-related utility instrument (EQ-5D). Information on hospital and clinic visit frequency, and continence pads use were also collected. Work productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire. Between group differences were assessed using ANOVA. Multivariable regression analyses were performed to examine the independent effects of OAB symptoms on QOL.
Severity of UI showed a significant linear relationship with QOL, with clinically meaningful differences between each UI severity category. Compared to the dry category, patients in the most severe category (≥4 UI/day) had significantly lower I-QOL scores (69.8 vs 42.6; p < 0.0001), greater symptom bother on the OAB-q (30.4 vs 64.6; p < 0.0001), and poorer EQ-5D utility (0.848 vs 0.742; p < 0.001). Multivariable analyses showed that UI severity, frequency, urgency, and nocturia are independently associated with poorer QOL. Incontinence severity is also significantly associated with cost of incontinence pads (p < 0.0001), and a greater interference with work and regular activities (p = 0.001), however, no significant difference in hospital and clinic visits were observed.
Severity of UI is a key contributor to the disease burden of OAB in Korean patients, even after taking into account the impact of other symptoms associated with OAB.
Electronic supplementary material
The online version of this article (doi:10.1186/s12955-015-0274-9) contains supplementary material, which is available to authorized users.
Overactive urinary bladder; Urinary incontinence; Quality of life; Cost of illness
Overactive bladder (OAB) causes urinary urgency, usually accompanied by frequency and nocturia. Alpha 1-adrenergic receptor (α1-AR) antagonists are known to improve lower urinary tract symptoms associated with OAB. The α1-AR antagonists constitute a variety of drugs according to the receptor subtype affinity. This study investigated the efficacy of tamsulosin, naftopidil, and a combination of the two on OAB rats.
The OAB rat model was induced by an intraperitoneal injection of cyclophosphamide for 14 days. The experimental groups were divided into 5 groups: control group, OAB-induction group, OAB-induction and tamsulosin monotherapy group, OAB-induction and naftopidil monotherapy group, and OAB-induction and tamsulosin-naftopidil combination therapy group. For the drug-treated groups, each drug was administrated for 14 days after the OAB induction. Cystometry for urodynamic evaluation and immunohistochemical stain for c-Fos and nerve growth factor (NGF) expressions in the central micturition centers were performed.
Increased contraction pressure and time with enhanced c-Fos and NGF expressions in the central micturition centers were found in the OAB rats. Tamsulosin suppressed contraction pressure and time while inhibiting c-Fos and NGF expressions. Naftopidil showed no significant effect and combination therapy showed less of an effect on contraction pressure and time. Naftopidil and combination therapy exerted no significant effect on the c-Fos and NGF expressions.
Tamsulosin showed the most prominent efficacy for the treatment of OAB compared to the naftopidil and combination. The combination of tamsulosin with naftopidil showed no synergistic effects on OAB; however, further studies of addon therapy might provide opportunities to find a new modality.
Urinary Bladder, Overactive; Tamsulosin; Naftopidil; c-Fos; Nerve Growth Factor
To evaluate the relationship between urodynamic detrusor overactivity (DO) and overactive bladder (OAB) symptoms in men and women.
We reviewed the records of adult males and females who attended a tertiary referral center for urodynamic evaluation of OAB syndrome symptoms with the presence or absence of DO. DO was calculated for symptoms alone or in combination.
The overall incidence of DO was 76.1% and 58.7% in male and female OAB patients, respectively. Of men 63% and 61% of women with urgency (OAB dry) had DO, while 93% of men and 69.8% of women with urgency and urgency urinary incontinence (OAB wet) had DO. Of women, 58% who were OAB wet had stress urinary incontinence symptoms with 26.4% having urodynamic stress incontinence. 6% of men and 6.5% of women with OAB symptoms had urodynamic diagnosis of voiding difficulties with postvoid residual greater than 100 mL. Combination of symptoms is more accurate in predicting DO in OAB patients. The multivariate disease model for males included urge urinary incontinence (UUI) and urgency while for females it included UUI and nocturia.
There was a better correlation in results between OAB symptoms and the urodynamic diagnosis of DO in men than in women, more so in OAB wet than in OAB dry. Combination of symptoms of the OAB syndrome seems to have a better correlation with objective parameters from the bladder diary, filling cystometry, and with the occurrence of DO.
Overactive bladder; Urodynamic investigation; Urinary incontinence; Detrusor overactivity
Overactive bladder (OAB), as defined by the International Continence Society, is characterized by a symptom complex including urinary urgency with or without urge incontinence, usually associated with frequency and nocturia. OAB syndrome has an incidence reported from six European countries ranging between 12-17%, while in the United States; a study conducted by the National Overactive Bladder Evaluation program found the incidence at 17%. In Asia, the prevalence of OAB is reported at 53.1%. In about 75%, OAB symptoms are due to idiopathic detrusor activity; neurological disease, bladder outflow obstruction (BOO) intrinsic bladder pathology and other chronic pelvic floor disorders are implicated in the others. OAB can be diagnosed easily and managed effectively with both non-pharmacological and pharmacological therapies. The first-line treatments are lifestyle interventions, bladder training, pelvic floor muscle exercises and anticholinergic drugs. Antimuscarinics are the drug class of choice for OAB symptoms; with proven efficacy, and adverse event profiles that differ somewhat.
Antimuscarinics; bladder training; overactive bladder
Introduction and hypothesis
The aim of this study was to measure physiologic and psychologic stress reactivity in women with overactive bladder (OAB). There is growing evidence in preclinical models that central nervous system dysregulation, particularly in response to psychological stress, may contribute to lower urinary tract symptoms in women with OAB.
Postmenopausal women with OAB and healthy controls underwent Structured Clinical Interview for DSM-IV Axis I disorders (SCID) to identify those without identifiable psychiatric disease. Eligible participants underwent physiologic measures including basal (cortisol-awakening response; CAR) and stress-activated salivary cortisol levels, heart rate (HR), urinary metanephrines and neurotrophins, as well as validated symptom assessment for stress, anxiety, depression, and bladder dysfunction at baseline and during, and following an acute laboratory stressor, the Trier Social Stress Test (TSST).
Baseline measures of cortisol reactivity measured by CAR showed blunted response among women with OAB (p = 0.015), while cortisol response to the TSST was greater in the OAB group (p = 0.019). Among OAB patients, bladder urgency as measured by visual analog scale (VAS) increased from pre- to post-TSST (p = 0.04). There was a main effect of TSST on HR (p < 0.001), but no group interaction.
Preliminary findings suggest that women with OAB have greater physiologic and psychologic stress reactivity than healthy controls. Importantly for women with OAB, acute stress appears to exacerbate bladder urgency. Evaluation of the markers of stress response may suggest targets for potential diagnostic and therapeutic interventions.
Overactive bladder; Cortisol; Stress; Hypothalamic–pituitary–adrenal axis
To evaluate the effect of caffeine at the dose of 4.5 mg/kg on bladder function in overactive bladder (OAB) adults.
Materials and Methods:
Nine women and three men aged 21-40 years with OAB symptoms were included. Each subject drank 8 ml/kg of water with and without caffeine at two separate sessions. Cystometry and uroflowmetry were performed 30 minutes after each drink. The effects of caffeine on urodynamic parameters were compared.
After caffeine ingestion, the mean volume at bladder filling phase decreased at first desire to void and normal desire to void (P<0.05), compared to the mean volume after taking water (control) drink. The mean volume at strong desire to void, urgency and maximum cystometric capacity also tended to decrease. No change in the detrusor pressure at filling phase was found. At voiding phase, the maximal flow rate, average flow rate and voided volume were increased (P<0.05). The urine flow time and time to maximal flow rate were not changed.
Caffeine at 4.5 mg/kg caused diuresis and decreased the threshold of sensation at filling phase, with an increase in flow rate and voided volume. So, caffeine can promote early urgency and frequency of urination. Individuals with lower urinary tract symptom should avoid or be cautious in consuming caffeine containing foodstuffs.
Caffeine; overactive bladder; uroflowmetry
Muscarinic receptors have long been the target receptors for treatment of patients with overactive bladder (OAB). These patients experience symptoms of urgency, urinary frequency and nocturia, with or without urge incontinence (the involuntary leakage of urine associated with urge). Fesoterodine, a pro-drug, structurally and functionally related to tolterodine, is the newest agent developed for the treatment of OAB. Fesoterodine is broken down to the active metabolite, 5-hydroxy-methyl-tolterodine (5-HMT) by non-specific esterases. This metabolism results in the complete breakdown of the parent compound and is responsible for dose related improvements in clinical efficacy and health related quality of life. Like other antimuscarinic agents including tolterodine, fesoterodine is associated with improvements in clinical variables related both to bladder filling (decreasing micturition frequency and increasing mean voided volume) and urgency (urgency and urge incontinence episodes). Improvements in health related quality of life following treatment with fesoterodine is indicated by improvements in 7 of the 9 variables measured by the King’s Health Questionnaire. Also like other antimuscarinic agents, fesoterodine use is associated with adverse events including dry mouth. However the incidence of dry mouth is reduced with fesoterodine, compared to oxybutynin, due to the improved bladder selectivity of 5-HMT.
fesoterodine; 5-hydroxymethy1-tolterodine; muscarinic; overactive bladder; urgency; incontinence
To evaluate the risk factors for overactive bladder (OAB) in a population aged 40 years and over in the community.
Materials and Methods
We conducted a community-based survey of OAB in a population aged 40 years and over in Guri City and Yangpyeong County, South Korea, by use of the overactive bladder symptom score (OABSS) questionnaire. A total of 926 subjects were included in the final analysis. The definition of OAB was more than 2 points for the urgency score and 3 points for the sum of scores. In addition, the subjects were asked about age, dwelling place, marital status, educational status, behavioral factors (smoking, drinking, etc), and medical history. Categorical variables were analyzed by using the logistic regression model and were adjusted for age by using the logistic regression model.
Overall OAB prevalence was 14.1% (130/926), made up of 49/403 males (12.2%) and 81/523 females (15.5%). OAB prevalence increased with age (p<0.0001). Risk factors for OAB were educational status (age-adjusted p=0.0487), stroke (p=0.0414), osteoporosis (p=0.0208), asthma (p=0.0091), rhinitis (p=0.0008), and cataract. Other factors (dwelling place, marital status, smoking, drinking, hypertension, diabetes, hyperlipidemia, myocardial infarction, angina, tuberculosis, atopic dermatitis, hepatitis B, and depression) were not associated with OAB.
The prevalence of OAB in our study was about 14.1% and the risk factors for OAB were educational status, stroke, osteoporosis, asthma, rhinitis, and cataract. Knowledge of these risk factors may help in the diagnosis and treatment of OAB.
Overactive bladder; Risk factors
To determine the relationship between overactive bladder symptoms and urodynamic verification of overactive bladder.
Material and Methods
Between June 2011 and November 2011, 159 patients underwent urodynamics (UDS) at our urogynecology unit in the Ege University Hospital. Of these, 95 patients who complained of urgency, did not have any overt neurological diseases, bladder outlet obstruction and did not take any medication affecting the lower urinary tract function were evaluated. SPSS (ver. 15.0) was used to evaluate the data and the chi-square test and t test for independent samples were used for analysis.
The mean age was found to be 54.5±12. Frequency was the most frequent symptom in women with overactive bladder (OAB) (82.1%), nocturia (57.8%) and (57.8%) urgency urinary incontinence followed in frequency. Detrusor over activity incidence was found to be 38.9%. There was no significant relationship between the presence of detrusor over activity (DOA) and OAB symptoms. Leak at urodynamics was found in 46.3% and there is no significant association with detrusor overactivity. Total bladder capacity was found to be significantly lower in women who had DOA (p=0.000).
It appears that overactive bladder symptoms do not predict detrusor over activity. Urodynamic investigation is not mandatory in the initial management of women with only OAB symptoms.
Overactive bladder; urodyamics; urgency urinary incontinence; detrussor over activity