Tamsulosin, an α1-adrenoceptor antagonist, and sildenafil, a phosphodiesterase (PDE) inhibitor, are reported to improve lower urinary tract symptoms including overactive bladder (OAB). This study is aimed at investing the effects of tamsulosin and sildenafil and comparing the degree of the suppressive effects on the afferent pathways of micturition between them using an animal model of OAB, the spontaneously hypertensive rat (SHR).
The cystometric parameters, the basal pressure and duration of bladder contraction, were significantly increased in the SHR group as compared with the Wistar-Kyoto (WKY) group. The intercontraction interval also significantly decreased in the SHR group. In the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group, however, the basal pressure and duration were significantly reduced and the intercontraction interval was significantly prolonged. Moreover, the degree of the expression of c-Fos and NGF was significantly higher in the SHR group as compared with the WKY group. But it was significantly reduced in the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group. Furthermore, tamsulosin had a higher degree of effect as compared with sildenafil.
In conclusion, α1-adrenergic receptor antagonists and PDE-5 inhibitors may have an effect in improving the voiding functions through an inhibition of the neuronal activity in the afferent pathways of micturition.
Overactive bladder syndrome; Tamsulosin; Sildenafil; Neuronal activity; Afferent pathways of micturition
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
Objectives. To investigate the add-on effect of solifenacin for Japanese men with remaining overactive bladder (OAB) symptoms after tamsulosin monotherapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) in real-life clinical practice. Methods. Patients aged ≥ 50 having remaining OAB symptoms (≥ 3 of OAB symptom score (OABSS) with ≥2 of urgency score) after at least 4 weeks treatment by 0.2 mg of tamsulosin for BPO/LUTS received 2.5 or 5.0 mg of solifenacin for 12 weeks. The International Prostate Symptom Score (IPSS), QOL index and OABSS, maximum flow rate (Qmax) and postvoid residual urine volume (PVR) were determined. Results. A total of 48 patients (mean age 72.5 years) completed the study. There were significant improvement in IPSS (15.1 to 11.2) and QOL index (4.2 to 3.0) by add-on of solifenacin. Although the IPSS storage symptom score was significantly improved, there were no changes observed in the IPSS voiding symptom score. The OABSS showed significant improvement (8.0 to 4.8). No changes were observed in Qmax and PVR. Conclusions. Under the supervision of an experienced urologist, the additional administration of solifenacin to patients with BPO/LUTS treated with tamsulosin, is effective in controlling remaining OAB symptoms.
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
To investigate the effects of early tamsulosin treatment on changes in bladder characteristics after a spinal cord injury.
We divided 45 rats into three groups: the control (CON) group, the spinal cord injury (SCI) group, and the SCI+tamsulosin treatment (SCI+TAM) group. Spinal cord transection was performed in the SCI and SCI+TAM groups. Tamsulosin was injected for 7 days in the SCI+TAM group. Intravesical and intra-abdominal catheters were implanted before cord injury. Basal pressure (BP), maximal vesical pressure (MVP), micturition volume (MV), and voiding interval time (VIT) were measured at 7 days after SCI. The bladder was then removed and used for an in vitro organ bath study and Western blot analysis. The percentage changes in contractility from baseline after acetylcholine alone, pretreatment with a muscarinic 2 (M2) receptor blocker (AQ-RA741), and pretreatment with a M3 receptor blocker (4-DAMP) were compared among the groups. Western blot analyses were performed to determine expression levels of pERK1/2 and rho-kinase.
In cystometry, MVP, BP, MV, and VIT showed changes in the SCI and SCI+TAM groups versus the CON group (p<0.05). In the organ bath study, acetylcholine-induced contractility in the three groups differed significantly (p<0.05). Additionally, acetylcholine-induced contractility with 4-DAMP pretreatment was reduced significantly in the SCI+TAM group versus the SCI group. In Western blotting, pERK1/2 expression was stronger (p<0.05) and rho-kinase expression was weaker in the SCI+TAM group than the SCI group (p<0.05).
These results suggest that the bladder contraction due to acetylcholine after SCI can be decreased by tamsulosin in the acute stage and this involves changes in pERK1/2 and rho-kinase.
Spinal cord injuries; Tamsulosin; Neurogenic urinary bladder
Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO.
Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction.
Cystometry showed that the intercontraction interval (ICI; 428.2±23.4 vs. 880.4±51.2, P<0.001), micturition pressure (MP; 25.7±1.01 vs. 71.80±3.01, P<0.001), and threshold pressure (2.9±0.25 vs. 9.2±1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group.
Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca2+ from the extracellular space or stores. The increase of Ca2+ probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.
TRPM8; Menthol; Cold receptor; Bladder outlet obstruction
Introduction and hypothesis
A study was conducted to assess associations between different overactive
bladder (OAB) symptoms and their outcomes on bladder diary and filling cystometry
We performed a retrospective cohort study in database of 6,876 Urinary
Distress Inventories, 3,185 bladder diaries and 2,153 filling cystometries from
women referred to our urogynecological center between 2003 and 2009. Women were
dichotomized into two groups. Group I: those women without symptoms, and those
with symptoms that were not bothersome. Group II: women with bothersome symptoms.
Data obtained from bladder diaries were: daytime urinary frequency, nocturnal
frequency, minimum voided volume, maximum voided volume, average voided volume,
and incontinence episodes. From filling cystometries, volumes at first desire to
void, normal desire to void, strong desire to void and maximum cystometric
capacity, were extracted. Univariate and multiple linear regression analysis were
performed to determine associations between OAB symptoms and bladder diary and
filling cystometry measurements.
After multivariate analysis the objective daytime frequency was most strongly
associated with the frequency symptom (β 0.27,
p < 0.05), night time frequency with the nocturia symptom (β
0.40, p < 0.05) and the number of
incontinence episodes with the urge incontinence symptom (β 0.37, p < 0.05). Both frequency and nocturia symptoms
were significantly associated with bladder diary and cystometry filling volumes,
and their effect size was the same. The urgency symptom proved to be poorly
associated with objective parameters.
In contrast to the frequency and nocturia symptom, the urgency symptom is
poorly associated with objective parameters on bladder diary and filling
cystometry. Therefore, the current practice of using frequency and incontinence
episodes in outcome research of OAB trials is justified.
Bladder diary; Cystometry; Overactive bladder
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
To better understand experts’ perceptions of the definition of overactive bladder (OAB), the evaluation of OAB, and treatment of OAB. OAB is defined by the International Continence Society as “urinary urgency, with or without urge urinary incontinence, usually with frequency and nocturia.” Under the current definition, people with very different clinical conditions fall under the OAB umbrella. With the goal of improving the care for women with OAB, we sought to better understand experts’ perceptions of OAB as it is presently defined.
Twelve interviews with leading urologic, gynecologic, and geriatric practitioners in urinary incontinence and OAB were performed. Questions were asked about their perception and agreement with the current definition of OAB. Interviews were audiotaped and transcribed verbatim. Grounded theory methodology was used to analyze the data.
Overall, there was a great deal of variability in defining and managing OAB. Four categories of definitions were derived from the qualitative analysis: current definition is adequate, OAB is a constellation of symptoms, should include the fear of leakage, and OAB is a marketing term. While there is some consensus on evaluation, several areas demonstrate disagreement over elements of the evaluation. Experts also felt that OAB is a chronic condition, with variability of symptoms, and it has no cure. Managing patient expectation is essential, as OAB is challenging to treat. A focus was placed on behavioral therapy.
There was disagreement among experts over the definition and work-up of OAB. However, experts agree that OAB is a chronic condition with a low likelihood of cure.
overactive bladder; urgency; urge incontinence; diagnosis; evaluation; management; definition
Purpose. We evaluated the effectiveness and safety of tamsulosin, solifenacin, and combination of both in reducing double-J stent-related lower urinary symptoms. Materials and Methods. A total of 338 patients with double-J ureteral stenting were randomly divided, postoperatively, into 4 groups. In group I (n = 84), no treatment was given (control group), group II (n = 85) received tamsulosin 0.4 mg daily, group III (n = 84) received solifenacin 10 mg daily, and group IV (n = 85) received a combination of both medications. Before insertion and 2 weeks after, all patients completed the International Prostate Symptom Score (IPSS), quality of life component of the IPSS (IPSS/Qol), Overactive Bladder Questionnaire (OAB-q), and Visual Analogue Pain Scale (VAPS) questionnaire. Results. The demographics and preoperative questionnaires scores of all groups were comparable. There were statistically significant differences in all scores in favour of groups II, III, and IV as compared to control group (P value < 0.005). Group IV showed statistically significant differences in total IPSS, QoL score, and OAB-q score as compared to groups II and III (P value < 0.001). Conclusions. Combined therapy of tamsulosin and solifenacin significantly alleviated lower urinary symptoms associated with double-J stents as compared to either medication alone.
We assessed the impact of transobturator tape (TOT) treatment on overactive bladder (OAB) symptoms with a particular focus on nocturia in patients with mixed urinary incontinence (MUI).
Materials and Methods
In this retrospective cohort study, the medical records of 237 women who underwent TOT surgery for the treatment of MUI were reviewed. Of these, 86 patients (36.4%) had preoperative nocturia. Patients with neurological diseases or sleep disorders that could affect the voiding pattern were excluded. Patients who were being treated with anticholinergics and antidiuretic hormones were also excluded, which left 70 subjects eligible for analysis. Pre- and postoperative evaluations consisted of a physical examination, 3-day frequency-volume chart, and health-related quality of life questionnaires (King's health questionnaire, overactive bladder symptom score, and OAB-questionnaire).
TOT treatment resulted in an overall significant improvement in OAB symptoms including nocturia. Frequency-volume charts revealed that TOT treatment significantly decreased the actual number of nightly voids (ANV) and the nocturnal bladder capacity index (NBCi) in the entire cohort. However, in a subgroup of women with nocturnal polyuria, there was no significant change in ANV or NBCi after the sling operation. Correlation analysis of the whole cohort revealed that the postoperative changes in NBCi correlated positively with postoperative changes in ANV. The nocturia-persisting group was more likely to have nocturnal polyuria and lower preoperative functional bladder capacity compared with the nocturia-improved group (p=0.024 and p=0.023, respectively).
Our results demonstrated that the TOT procedure resulted in an overall significant improvement in OAB symptoms including OAB-related nocturia in patients who presented with MUI.
Nocturia; Questionnaires; Transobturator tape; Stress urinary incontinence
To determine whether neuregulin-1(NRG-1) is a potential new biomarker of overactive bladder (OAB) induced by partial urethral obstruction in a rat model of OAB and to evaluate the urothelium as a therapeutic target of OAB.
Female Sprague–Dawley rats were separated into three 20-animal groups: normal, OAB, and 5-hydroxymethyl tolterodine (5-HMT)-treated OAB. In the OAB and OAB + 5-HMT groups, the urethra of each animal was partially obstructed; the OAB + 5-HMT group received intravenous 5-HMT for 3 weeks. At the conclusion of the 5-HMT dosing, the rats in each group underwent cystometrography, and the bladders were histologically evaluated. The expression of brain derived-neurotrophic factor (BDNF) and NRG-1 were evaluated in the urothelium.
Compared with the control group, the OAB group showed a markedly increased bladder weight and a significant decrease in the micturition interval and volume; rats in the OAB + 5-HMT group showed decreased bladder weights and an improved micturition interval and volume. BDNF and NRG-1 were expressed at significantly higher levels in the OAB group, and were significantly reduced in the OAB + 5-HMT group compared with the control group.
The study suggests that NRG-1 is a potential new biomarker of OAB; the urothelium might be a therapeutic target for OAB treatment.
Neuregulin-1; Overactive bladder; Biomarker
Recent studies have shown that chronic inflammation is involved in overactive bladder (OAB) syndrome. OAB could be a subtype of neurogenic inflammation. This pilot study investigated serum adipokine levels in patients with OAB refractory to antimuscarinic therapy.
Thirty consecutive patients with OAB-dry (n = 16) or OAB-wet (n = 14) refractory to previous antimuscarinic treatment were prospectively enrolled in this study, a group of 26 normal subjects without lower urinary tract symptoms served as controls. Concentrations of serum C-reactive protein (CRP), nerve growth factor (NGF), and adipokines including interleukins ([IL], IL-1β, IL-6, IL-8), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, insulin, and leptin were quantified using a bead-based human serum adipokine panel B kit. Data were analyzed using the LX 200 platform. Patients were further classified as having dry or wet OAB and having medical diseases or not. The serum CRP, NGF, and adipokine levels were compared between OAB patients and the controls, and between OAB subgroups.
The serum concentrations of CRP, NGF, IL-1β, IL-6, IL-8, and TNF-α in OAB-dry and OAB-wet patients were significantly higher than among the controls. There was no significant difference in adipokine levels between OAB-dry and OAB-wet, or between OAB patients with and without medical diseases. Serum CRP and NGF levels were significantly higher only in OAB-wet or OAB patients with medical diseases than among controls. The MCP-1 levels, on the other hand, were significantly higher in OAB-dry or OAB patients with disease, than the controls.
Both OAB-dry and OAB-wet patients showed increased serum CRP, NGF, and adipokine levels compared with the controls, suggesting chronic inflammation of the bladder involving both peripheral and central mechanisms in all OAB patients refractory to antimuscarinic therapy. The increased serum adipokine levels were not relevant to medical diseases.
Intravesical injection of onabotulinumtoxinA is an effective treatment for overactive bladder (OAB). Nonetheless, the treatment outcome is unclear in OAB patients with central nervous system (CNS) lesions. This study evaluated the efficacy and safety of intravesical onabotulinumtoxinA treatment in elderly patients with chronic cerebrovascular accidents (CVAs), Parkinson’s disease (PD) and dementia.
Materials and Methods
Patients with CVA, PD, dementia, and OAB refractory to antimuscarinic therapy were consecutively enrolled in the study group. Age-matched OAB patients without CNS lesions were selected to serve as a control group. OnabotulinumtoxinA (100 U) was injected into the bladder suburothelium at 20 sites. The clinical effects, adverse events, and urodynamic parameters were assessed at baseline and 3 months post-treatment. The Kaplan-Meier method was used to compare long-term success rates between groups.
A total of 40 patients with OAB due to CVA (23), PD (9), dementia (8) and 160 control patients were included in this retrospetive analysis. Improvement of urgency severity scale, increased bladder capacity and increased post-void residual volume were comparable between the groups at 3 months. Patients with CNS lesions did not experience increased risks of acute urinary retention and urinary tract infection; nonetheless, patients with CVA experienced a higher rate of straining to void. Long-term success rates did not differ between the patients with and without CNS lesions.
Intravesical injection of 100 U of onabotulinumtoxinA effectively decreased urgency symptoms in elderly OAB patients with CNS lesions. The adverse events were acceptable, and long-term effects were comparable to OAB patients in general. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization need careful evaluation for this very vulnerable population before choosing intravesical onabotulinumtoxinA treatment.
In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments.
Materials and Methods:
A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options.
In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted.
The vast majority of OAB patients can be managed successfully by behavioral options with or without anticholinergic medications. When those fail, neuromodulation or intravesical botulinum toxin therapies are successful alternatives for most of the remaining group. We encourage practitioners responsible for the care of OAB patients to gain experience with these options. More research is needed to assess the cost-effectiveness of various OAB treatments
Behavioral therapy; botulinum toxin type A; electrical stimulation; overactive bladder; urinary incontinence; urologic surgical procedures
It has been previously demonstrated that adipose tissue-derived stem cell (ADSC) can differentiate into muscle and neuron-like cells in vitro. In this study, we investigate the utility of ADSC in the treatment of overactive bladder (OAB) in obese hyperlipidemic rats (OHR).
Materials and Methods
Hyperlipidemia was induced in healthy rats by administration of a high fat diet. The resulting OHR were then treated with bladder injection of saline or ADSC or tail vein injection of ADSC. Bladder function was assessed by 24-h voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining followed by image analysis.
Serum total cholesterol and low-density lipoprotein levels were significantly higher in OHR than in normal rats (p < 0.01). Micturition intervals were shorter in the saline-treated OHR relative to normal rats, OHR that received ADSC via tail vein, and OHR that received ADSC by bladder injection (143 ± 28.7 vs 407 ± 77.9 vs 281 ± 43.9 vs 368 ± 66.7 seconds respectively, p = 0.0084). Smooth muscle content of the bladder wall was significantly lower in OHR than in normal animals (p = 0.0061) while there was no significant difference between OHR groups. Nerve content and blood vessel density were lower in control than in ADSC-treated OHR.
Hyperlipidemia is associated with increased urinary frequency and diminished bladder blood vessel and nerve density in rats. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for OAB.
Adipose tissue-derived stem cells; lower urinary tract symptoms; obese hyperlipidemic rat; overactive bladder
To investigate the expression of four subtypes of E-series prostaglandin (EP1–EP4) receptors and the urodynamic effects of an EP4 receptor antagonist (AH23848) in cyclophosphamide (CYP)-induced overactive bladder (OAB) in rats, as intravesical prostaglandin E2 (PGE2) induces OAB via activation of EP receptors and sensitization of afferent nerves.
MATERIALS AND METHODS
Experimental and control rats were injected with CYP (200 mg/kg, intraperitoneally) or saline, respectively. Continuous cystometrograms (CMGs) were performed 48 h after CYP or saline injection under urethane anaesthesia. AH23848 was given intravenously at doses of 0.01 and 0.1 mg/kg. The bladder was then harvested for histology. Some bladders were harvested for analysis of EP receptors expression by Western blotting without a CMG study. CMG variables (baseline pressure; intercontraction interval [ICI], pressure threshold [PT], contraction amplitude) and histological changes were measured.
CYP-induced up-regulation of EP4 receptor (100% increase) accompanied by detrusor overactivity (ICI 70.5% decrease; PT, 67.7% increase). However, CYP down-regulated EP1 receptor expression (51.9% decrease), but had no significant effects on the EP2 and EP3 receptors. AH23848 significantly extended the ICI in CYP-treated rats but it had no effects on other urodynamic variables or in control rats.
Modulation of EP receptors plays a role in CYP-induced OAB. Antagonists to the EP4 receptor may be a new target for treatment of patients with OAB.
EP4 receptor; cyclophosphamide; overactive bladder; rat
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
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
Prospective randomized study to compare the efficacy and safety of alfuzosin and tamsulosin in patients suffering from acute urinary retention caused by benign prostatic hyperplasia (BPH).
Patients with acute urinary retention (AUR) due to BPH (total 150) were catheterized and randomized into three groups: Group A: alfuzosin 10 mg (50 patients), Group B: tamsulosin 0.4 mg (50 patients), Group C: placebo (50 patients). After three days, catheter was removed, and patients were put on trial without catheter (TWOC). Patients with successful TWOC were followed up for three months, taking into account the prostate symptom score (AUA Score), post-void residual urine volume (PVRV), and peak flow rate (PFR). ANOVA was used for statistical analysis.
Both group A (alfuzosin) and group B (tamsulosin) had similar results of TWOC (group A – 66%, group B – 70%), which were significantly superior than group C (placebo) – 36%. In follow up, three (9.1%) patients in group A, three (8.6%) patients in group B and eight (44.4%) patients in group C had retention of urine, requiring recatheterization. These patients were withdrawn from the study. After three months, alfuzosin- or tamsulosin-treated patients showed a significant decrease in AUA score and PVRV; and a significant increase in PFR as compared to placebo.
TWOC was more successful in men treated with either alfuzosin or tamsulosin and the subsequent need for recatheterization was also reduced. Tamsulosin was comparable to alfuzosin in all respects, except a small but significant side effect of retrograde ejaculation.
Acute urinary retention; alfuzosin; BPH; trial without catheter; tamsulosin
Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs including cognitive changes.
To investigate the effect of an anticholinergic medication on cognitive function in postmenopausal women being treated for OAB.
Prospective cohort study conducted from January to December 2010, with 12-week follow-up after medication initiation.
Urogynecology clinic at one academic medical center.
Women age 55 or older seeking treatment for OAB and opting for anticholinergic therapy were recruited.
Baseline cognitive function was assessed via the Hopkins Verbal Learning Test – Revised Form (HVLT-R) (and its 5 subscales), the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality of life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance.
Main Outcome Measure
Change in HVLT-R score at Week 4 after medication initiation, compared to baseline (pre-medication) score.
Of 50 women enrolled, 35 completed the assessment. Average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p=0.037), HVLT-R Delayed Recognition subscale (p=0.011) and HVLT-R Recognition Bias subscale (p=0.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p=0.029). All HVLT-R scores normalized by Week 4. OMC remained stable throughout. The Mini-Cog nadired at a 90.9% pass rate at Week 4. OAB symptoms did not improve until Week 4, based on questionnaire scores (p<0.05).
Cognitive function exhibited early changes after initiation of trospium chloride but normalized within four weeks. Cognitive changes occurred weeks prior to OAB symptom improvement. Surveillance for cognitive changes with anticholinergic use should be part of OAB management.
Anticholinergic; Cognitive Function; Elderly; Overactive Bladder
To evaluate the efficacy and tolerability of tamsulosin 0.4 mg once daily in Korean patients with symptomatic benign prostatic hyperplasia (BPH) and investigate whether tamsulosin 0.4 mg can improve symptoms in patients with refractory lower urinary tract symptoms (LUTS) who were previously receiving tamsulosin 0.2 mg once daily.
Materials and Methods
A total of 116 patients from 3 urology centers participated. All study subjects entered a nonblind phase consisting of 8 weeks of tamsulosin 0.2 mg monotherapy followed by an additional 8 weeks of tamsulosin 0.2 mg (0.2 mg group) or 8 weeks of tamsulosin 0.4 mg (0.4 mg group). At week 8, we chose the 0.4 mg group on the basis of International Prostate Symptom Score (IPSS), quality of life (QoL), maximal urinary flow rate (Qmax), and adverse effects. At week 16, we compared the efficacy and tolerability of tamsulosin between the 0.2 and 0.4 mg groups.
A total of 26 patients (22.4%) were escalated to tamsulosin 0.4 mg at week 8. There were significant differences in IPSS, QoL, and Qmax at week 8 in both groups. There were significant differences in improvement in IPSS, QoL, Qmax, and postvoid residual urine volume from baseline to week 16 in both groups. There were no significant differences in efficacy or tolerability between the groups at week 16.
Our trial demonstrated that tamsulosin 0.4 mg has favorable efficacy and tolerability in Korean patients with symptomatic BPH refractory to tamsulosin 0.2 mg. No patients experienced any serious adverse effects when we escalated the dose of tamsulosin to 0.4 mg.
Prostatic hyperplasia; Tamsulosin
Overactive bladder (OAB) is a symptom syndrome including urgency, frequency, and nocturia – with or without incontinence. It is a common manifestation of detrusor overactivity (DO). DO is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. OAB is, therefore, both a motor and sensory disorder. Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum and has been used in medicine for many years. Over the last 10 years, it has been used for the treatment of DO and OAB when standard treatments, such as bladder training and oral anticholinergic medication, have failed to provide symptom relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release from the neurons in the motor end plate and also at sensory synapses, although the clinical effect is not permanent due to the growth of new connections within treated tissues. It is known that botulinum toxin modulates vanillioid, purinergic, capsaicin, and muscarinic receptor expression within the lamina propria, returning them to levels seen in normal bladders. Clinically, the effect of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon the symptom of urgency, and also large effects on frequency, nocturia, leakage episodes, and continence rates. These effects have been seen consistently within eight randomized trials and numerous case series. Botulinum toxin appears safe, with the only common side effect being that of voiding difficulty, occurring in up to 10% of treated patients. Dosing regimens are variable, depending on which preparation is used, but it is clear that dose recommendations have fallen over the last 5 years. There is limited evidence about the efficacy of repeat treatments. Botulinum toxin is an effective and safe second-line treatment for patients with OAB and DO.
overactive bladder; detrusor overactivity; botulinum toxin; efficacy; side-effects; treatment
We compared the effectiveness of the retropubic tension-free vaginal tape (TVT) and the transobturator inside-out tape (TVT-O) in treating symptoms of overactive bladder (OAB) in women with stress urinary incontinence (SUI).
Women with urodynamic SUI and OAB (mean urgency episodes ≥1 and frequency ≥8/24 hours on a 3-day voiding diary) were assigned to the TVT or TVT-O group. Preoperative measures were based on a urodynamic study, 3-day voiding diary, the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTSSF), and the urgency perception scale (UPS). At 12 postoperative months, the 3-day voiding diary, symptoms questionnaire, patient satisfaction, and standing stress test were assessed. The primary endpoint was change in the number of urgency episodes/24 hours from baseline to 12 months.
In this group of 132 women, 42 received TVT and 90 received TVT-O. The mean urgency episodes/24 hours decreased from 6.3±5.5 to 1.6±3.2 in the TVT group and from 5.1±4.4 to 1.8±3.0 in the TVT-O group. The mean percent change was significantly greater after TVT than after TVT-O (73% vs. 60%, P=0.049). All subscales of BFLUTSSF and UPS were significantly improved using either method, with significantly greater improvement seen in the quality of life (QoL) domain after TVT (P=0.002). There were no significant differences in the cure and satisfaction rates between the two groups.
Intervention with the TVT or the TVT-O significantly improved symptoms of OAB in women with SUI and OAB. Urgency and QoL significantly improved after TVT compared with that after TVT-O.
Overactive urinary bladder; Stress urinary incontinence
We aimed to estimate the prevalence of overactive bladder (OAB) in Korea, to assess the variation in prevalence by sex and age, and to measure the impact of OAB on quality of life.
A population-based, cross-sectional telephone survey was conducted between April and June 2010 with a questionnaire regarding the prevalence of OAB, demographics, and the impact of OAB on quality of life. A geographically stratified random sample of men and women aged ≥30 years was selected.
The overall prevalence of OAB was 22.9% (male, 19%; female, 26.8%). Of a total of 458 participants with OAB, 37.6% and 19.9% reported moderate or severe impact on their daily life and sexual life (5.6% and 3.5%, respectively, in participants without OAB). Anxiety and depression were reported by 22.7% and 39.3% of participants with OAB, respectively (9.7% and 22.8%, respectively, in participants without OAB). Only 19.7% of participants with OAB had consulted a doctor for their voiding symptoms, but 50.7% of respondents with OAB were willing to visit a hospital for the management of their OAB symptoms.
This study confirmed that OAB symptoms are highly prevalent in Korea, and many sufferers appear to have actively sought medical help. OAB has severe effects on daily and sexual life as well as psychological health.
Overactive urinary bladder; Prevalence; Demography