Does local vaginal estrogen after tension-free transobturator vaginal tape reduce overactive bladder symptoms in postmenopausal women? A prospective randomized, controlled study

Objective:We aimed to evaluate the efficacy of topical estrogen after transvaginal tension-free vaginal tape-obturator(TVT-O)in the treatment of de novo overactive bladder symptoms that appear after surgery.Methods:This is a prospective randomized controlled study performed in the Urology and Gynecology Departments,Kasr Al Ainy Hospital,Cairo University,Cairo,Egypt.Two hundred and ten postmenopausal females presenting during the period between January 2017 and November 2020 with stress urinary incontinence were included in the study.Patients were divided into two groups,105 patients in Group A(treatment group)and 105 patients in Group B(control group).Patients in Group A underwent transvaginal TVT-O followed by local vaginal estrogen treatment for 6 months,while patients in Group B underwent transvaginal TVT-O only.The study included any postmenopausal female with urodynamic stress urinary incontinence.All patients had to fulfill a 3-day bladder diary,overactive bladder symptoms score,urine analysis,urodynamic study,and post-voiding residual urine measurement by abdominal ultrasound preoperatively and at 3-month and 6-month follow-ups.Results:At 6-month follow-up,daytime frequency was reduced to 8%in Group A(increased to 21%in Group B)with a statistically significant difference between both groups(p=0.009).At 6-month follow-up,nocturia was 8%in Group A(11%in Group B)with no statistically significant difference between both groups(p=0.469).There was a statistically significant difference between both groups as regards to urinary urgency at 6-month follow-up(p=0.024).There was a statistically significant difference in postoperative wound healing events as regards to cure,hyperemia,gapping,and wound infection 1 week after intervention between both groups(p=0.008).No local or systemic side-effects were reported from local estrogen use.Conclusion:Local vaginal estrogen treatment given to postmenopausal patients after midurethral sling procedures can reduce the symptoms of daytime frequency and urinary urgency.Long-term follow-up is needed.

Pioneering drugs for overactive bladder and detrusor overactivity: Ongoing research and future directions

The ongoing research on pioneering drug candidates for the overactive bladder （OAB） aimed to overcome the limitations of currently licensed pharmacotherapies, such as antimuscarinics, β3-adrenergic agents, and botulinum neurotoxin, has been reviewed performing a systematic literature review and web search. The review covers the exploratory agents alternative to available medications for OAB and that may ultimately prove to be therapeutically useful in the future mana-gement of OAB patients based on preclinical and early clinical data. It emerges that many alternative pharmacological strategies have been discovered or are under investigation in disease-oriented studies. Several potential therapeutics are known for years but still fnd obstacles to pass the clinical stages of development, while other completely novel compounds, targeting new pharmacological targets, have been recently discovered and show potential to translate into clinical therapeutic agents for idiopathic and neurogenic OAB syndrome. The global scenario of investigational drugs for OAB gives promise for the development of innovative thera-peutics that may ultimately prove effective as first, combined or second-line treatments within a realistic timescale of ten years.

Does an “Overactive to Underactive Bladder Transition” Phenomenon Exist in a Rat Lumbar Spinal Canal Stenosis Model?

Purpose: To investigate the association between the maximum cystometric capacity (MCC) and other cystometric parameters in lumbar canal stenosis (LCS) rats. Material and Methods: One small hole was drilled at the fifth lumbar vertebral arch (Sham), and a rectangular piece of silicone rubber was then placed in the epidural space (LCS) of Wister rats. Two weeks after surgery, awake cystometry was performed. LCS rats were divided into three groups: Group A (n = 5, MCC < 0.87 mL), Group B (n = 13, MCC 0.87 - 1.81 mL), and Group C (n = 14, MCC > 1.81 mL). Cystometric parameters were investigated in sham and LCS groups. Results: MCC did not significantly correlate to the frequency of non-voiding contractions (NVCs), voided volume (VV), or maximum intravesical pressure during voiding (Pmax), but significantly positively correlated to postvoid residual urine volume (PVR) and residual urine rate (RUR) (Spearman’s correlation coefficients (ρ) = 0.8973 (p < 0.0001) and 0.4915 (p = 0.0068), respectively). Compared with the sham rats, LCS rats in each group revealed significantly smaller VV, larger RUR, and lower Pmax. On the other hand, among LCS rats, VV, RUR, and Pmax were not significantly different. The frequency of NVCs in each LCS group was not significantly different from that in sham-operated rats (Tukey-Kramer’s HSD test). However, a Jonckheere-Terpstra trend test revealed a significant trend toward higher NVCs in the order of sham, Groups C, B, and A (p = 0.036). Conclusions: LCS rats showed the same degree of detrusor underactivity regardless of MCC. NVCs did not significantly increase in LCS rats with decreased MCC, but the trend toward higher NVCs with smaller MCC was significant.

A nurse-led long-term pelvic floor muscle training program in the management of female patients with overactive bladder e A study protocol for a randomized controlled trial

Background:Previous research has suggested that pelvic floor muscle training(PFMT)offers a therapeutic benefit in patients with overactive bladder.Methods:Weconducted a single-blind,randomized trial of pelvic floor muscle training(PFMT)as compared with usual care.The intervention group(n=54)received a 6-month a nurse-led long-term pelvic floor muscle training program(three sessions a day,15e20 times per session)and the control group(n?53)received usual care.All patients received 3-month solifenacin succinate tablets(5 mg e once daily).The treatment outcomes were measured by the Modified Oxford Scale(MOS),Overactive Bladder SymptomScore(OABSS)and the King's Health Questionnaire(KHQ)at baseline,3 months and 6 months respectively.Results:Of the 91 randomly assigned patients,46 patients in the PFMT group and 45 patients in the control group completed the trial.The trial revealed statistically significant differences between groups in pelvic muscle strength at 3 months following the intervention(p<0.05),but no significant difference was found between two groups in OABSS scores(p>0.05).In regards to quality of life,the experimental group showed significant improvements compared to the control group on 6 of 10 domains(p<0.05).At 6 months,there were significant improvements in OABSS scores and quality of life in the experimental group compared to the control group(p<0.05).No adverse events were observed.Conclusion:A nurse-led long-term(6 months)pelvic floor muscle training program may alleviate OAB symptoms effectively and improve the quality of life more than a short term(3 months)pelvic floor muscle training program combined with solifenacin succinate tablets.

Non-invasive transcutaneous electrical stimulation in the treatment of overactive bladder

We reviewed the literature on transcutaneous electrical nerve stimulation(TENS)used as a therapy for overactive bladder(OAB)symptoms,with a particular focus on:stimulation site,stimuli parameters,neural structures thought to be targeted,and the clinical and urodynamic outcomes achieved.The majority of studies used sacral or tibial nerve stimulation.The literature suggests that,whilst TENS therapy may have neuromodulation effects,patient are unlikely to benefit to a significant extent from a single application of TENS and indeed clear benefits from acute studies have not been reported.In long-term studies there were differences in the descriptions of stimulation intensity,strategy of the therapy,and positioning of the electrodes,as well as in the various symptoms and pathology of the patients.Additionally,most studies were uncontrolled and hence did not evaluate the placebo effect.Little is known about the underlying mechanism by which these therapies work and therefore exactly which structures need to be stimulated,and with what parameters.There is promising evidence for the efficacy of a transcutaneous stimulation approach,but adequate standardisation of stimulation criteria and outcome measures will be necessary to define the best way to administer this therapy and document its efficacy.

Efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder and nocturia, current clinical features and outcomes: A systematic review

Objective To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder(OAB)and nocturia.Methods A selective database search was conducted to validate the effectiveness of desmopressin in patients with OAB and nocturia.Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilised.The meta-analysis included 378 women(five studies)with OAB.The clinical outcomes and adverse events were analysed.Results The treatment strategy of all the studies included can be divided into three categories:(1)The effect of desmopressin compared with baseline,(2)desmopressin compared with placebo,and(3)desmopressin and anticholinergic combination versus desmopressin monotherapy.There was a significant(50%)reduction in nocturia and urgency episodes after using desmopressin alone.Combined desmopressin and anticholinergic led to a decrease in the frequency of nocturia voids when only using anticholinergic(65%vs.33.2%).The time increased in the middle to the first nightly voids in the combination arm(65.11 min;p=0.045).The mean incidence(standard deviation)of leak-free episodes was higher under desmopressin than under placebo in the first 4 h(62%[35%]vs.48%[40%])and in the first 8 h(55%[37%]vs.40%[41%]).The safety profile was comparable between treatments.Conclusion Available data indicate that desmopressin is efficacious in significantly reducing nighttime urine production,episodes of nocturia,and urgency episodes.The affectivity of the combination therapy was very high with least side effects for the treatment of OAB/nocturnal polyuria.

Association of advanced glycation endproduct accumulation with overactive bladder in community-dwelling elderly: A cross-sectional Sukagawa study

Objective:This study aimed to evaluate the influence of advanced glycation end-product(AGE)accumulation on the prevalence and severity of overactive bladder(OAB)in community-dwelling elderly adults.Methods:We conducted a cross-sectional study involving 269 Japanese community dwellers aged≥75 years in 2015.AGE accumulation was non-invasively measured via skin autofluorescence(SAF)values using AGE Reader.The primary and secondary outcomes were the presence and severity of OAB evaluated using the Overactive Bladder Symptom Score(OABSS).Individuals with an urgency score of≥2 and sum score of≥3 were considered to have OAB.The associations of SAF with the prevalence and severity of OAB were assessed using logistic and linear regression models,respectively,adjusted for clinically important confounders.Results:The median age of participants was 78 years.Of 269 participants,110(40.9%)were men and 75(27.9%)had OAB.The median SAF was 2.2 arbitrary units(AUs).Increasing median SAF was observed with increasing age.Multivariable analysis revealed that SAF was not associated with either the likelihood of having OAB(odds ratio per AU=0.77,95%confidence interval:0.37-1.62)or the natural log-transformed OABSS(0 per AU=-0.07,95%confidence interval:-0.26-0.12).Conclusions:In this study,AGE accumulation,as assessed by SAF,was not associated with the prevalence and severity of OAB in Japanese community-dwelling elderly people aged≥75 years.

Very Low, Real-Time Rate of Urinary Retention after Intradetrusor Botox^&regfor Non-Neurogenic Overactive Bladder

Introduction: According to the most recent AUA/SUFU guidelines, intradetrusor onabotulinumtoxinA (BTN/A) is a standard, evidence strength grade B, third line treatment option for refractory non-neurogenic overactive bladder (OAB). Urinary retention is the most common clinically significant reported side effect ranging from 5.4% to 43% in previous studies. The aim of this study was to investigate the real-time rate of urinary retention in patients treated with BTN/A for refractory non-neurogenic OAB in a multi-institutional study. Methods: Retrospective chart review identified 71 patients who were treated with 100U BTN/A for refractory non-neurogenic OAB from August 2011 to July 2015 at two institutions. Using a flexible cystoscope, 100U Botox&reg reconstituted with 10 ml normal saline was administered. Injections of 1 ml (10 units/ mL) were administered in 10 evenly distributed sites sparing the trigone. Pre and post BTN/A post-void residuals (PVR) were reviewed. Urinary retention was defined as PVR > 200 mL requiring clean intermittent catheterization (CIC). Results: After exclusion, the study group consisted of 66 patients with a mean age of 67 years and 30% were men. Mean pre and post-procedural PVR were 14.06 mL and 69.21 mL. Eight patients (12.12%) were noted to have elevated PVR > 200 mL post injection however only one patient (female) required initiation of CIC. The rate of urinary retention was 1.5% (N = 1). There was no correlation with age, history of previous radiation, diabetes or prior use of a neuromodulator device. Conclusions: To the best of our knowledge, this is the first study to demonstrate a very low risk of real-time urinary retention rates in appropriately selected patients treated with BTN/A for refractory non-neurogenic OAB outside of a clinical trial setting.

Comparative assessment of efficacy and safety of different treatment for de novo overactive bladder children: A systematic review and network meta-analysis

Objective:To compare these managements focusing on the efficacy and safety to treat overactive bladder(OAB)in children through network meta-analysis(NMA).Methods:We searched PubMed,Embase,the Cochrane Library Central Register of Controlled Trials(CENTRAL)and the reference lists up to May 1st,2017.Data from eligible randomized controlled trails(RCT)studies including three different treatment options were extracted.The primary outcome was maximal voiding volume(MVV).We performed pairwise metaanalyses by random effects model and NMA by Bayesian model.We used the Grading of Recommendations,Assessment,Development and Evaluations(GRADE)framework to assess the quality of evidence contributing to each network estimate.Results:Six RCTs(462 patients)comparing three different interventions fulfilled the inclusion criteria.A low risk of bias was shown for the majority of the study items.The results of NMA showed that compared with antimuscarinic drugs,Parasacral transcutaneous electrical nerve stimulation was associated with significant improvement in the MVV(mean difference[MD]=58.50,95% confidential interval[CI]:45.95-69.52),followed by urotherapy group(MD=21.03,95%CI:11.85-29.97).When it comes to the constipation,antimuscarinic drugs exerted significant benefit than PTENS(odds ratio[OR]:0.22,95%CI:0.01-0.46).No significant difference was found between other treatments.Conclusion:Compared with antimuscarinic drugs,PTENS was associated with significant better efficacy considering MVV,but more constipation events in de novo OAB children.Antimuscarinic drugs showed remarkably better efficacy considering MVV and comparable safety profile compared with urotherapy.Clinicians should take all known safety and compliance of patients into account when choosing an optimal strategy.

Efficacy and safety of onabotulinum toxin A for overactive bladder

Overactive bladder(OAB) syndrome is a condition which affects 16.9% of women and 16.2% of men with a significant negative impact on quality of life. It is a condition characterized by urgency, with or without urge incontinence, frequency and nocturia. Behavioral modifications and oral anti-muscurinic medications are first and second-line therapies for OAB but are frequently ineffective or poorly tolerated. For refractory cases of OAB, onabotulinum toxin can be offered and this therapy was approved by the Food and Drug Administration in January of 2013. In this editorial, we will review the indications, usage, efficacy and safety data for intradetrusor injection of onabotulinum toxin A.

Mirabegron, a novel, non-antimuscarinic drug for the overactive bladder: An up-to-dated review

Mirabegron opened a new era in the treatment of overactive bladder(OAB). For the fi rst time physicians dealing with OAB have an effective alternative to the pharmacological mainstay of the therapy for this disorder, the antimuscarinic drugs. This fi rst-in-class, potent β3-adrenoceptors agonist has recently received approval by regulatory authorities in Japan, United States and Europe, based on the favourable efficacy-tolerability profile demonstrated in multiple randomized, multinational, controlled trials, both short and long-term. There is substantial consistency through the studies in reporting the cardiovascular safety of treatment with mirabegron. The main advantage of mirabegron is the placebo-like incidence of classic adverse effects caused by antimuscarinics, dry mouth and constipation, that is expected to improve long-term adherence of patients to treatment. Mirabegron can be used in patients with contraindications to antimuscarinics and in those who discontinued previous antimuscarinic therapy. Herein, we reviewed the published literature on mirabegron, focusing on the rationale of β3-agonism for OAB treatment and on the preclinical and clinical evidence of effi cacy and safety available on this new pharmacological principle.

Effects of solifenacin on overactive bladder patients

Objective To investigate the effects of solifenacin on the detrusor instability of patients with overactive bladder ( OAB ) . Methods A total of 20

Clinical study of combination therapy of tamsulosin and solifenacin for benign prostatic hyperplasia with overactive bladder

Objective To evaluate the efficacy and safety of combination therapy of tamsulosin and solifenacin for benign prostatic hyperplasia ( BPH) with overactive bladder ( OAB) . Methods 82 patients with OAB and coexisting BPH were randomly divided into tamsulosin group ( n

Efficacy of solifenacin with or without tamsulosin in patients with overactive bladder

Objective To evaluate the efficacy of sollfenacin with or without tamsulosin in patients with overactive bladder ( OAB ) . Methods Fifty-three patients with OAB were randomly divided into two groups ( group

Acupuncture for overactive bladder in adults:Study protocol for a randomized controlled trial

Background:Overactive bladder(OAB)is a prevalent condition that substantially degrades patient quality of life.Acupuncture is recognized as an effective therapeutic approach for various urological diseases.However,there is limited evidence validating the effectiveness and safety of acupuncture for OABs.Objective:To assess the therapeutic efficacy of acupuncture for OAB and to investigate the potential mechanisms by analyzing its effects on relevant urinary biomarkers.Methods:This is a randomized,participants and outcome assessors blinded,sham acupuncture controlled trial.A total of 110 patients with OABs will be randomly divided in a 1:1 ratio between the acupuncture and sham acupuncture groups.Participants in the acupuncture group will undergo 30-min authentic acupuncture,while their counterparts in the sham acupuncture group will undergo sham acupuncture needling non-acupoints superficially three times weekly for a duration of 8 weeks.The two co-primary outcomes will be the change in the mean number of micturitions per 24 h from baseline to the end of the 8-week treatment and 20-week follow-up.The secondary outcomes will encompass the change in Overactive Bladder Symptom Score,Overactive Bladder Questionnaire Short Form,and average 24 h values of urgency,daytime micturition,nocturia,and mean volume voided per micturition from baseline to weeks 8 and 20.Urinary nerve growth factor,brain-derived neurotrophic factor,and monocyte chemoattractant protein-1 levels will be measured at baseline and week 8.Adverse events will also be documented.Discussion:The results of this trial will provide evidence for the effectiveness and safety of acupuncture in the management of OAB.

The role of botulinum toxin in the management of nonneurogenic overactive bladder in children:Highlights for clinical practice.A systematic review

Overactive bladder(OAB)is the most common voiding dysfunction in children;however,nonneurogenic or idiopathic OAB remains poorly studied.First-line treatment includes conservative measures;however,as many patients are refractory,have adverse effects,or are contraindicated for anticholinergics,new options must be explored.This review covers the use of intravesical botulinum toxin(BoNT)for idiopathic OAB treatment in children,emphasizing its efficacy,safety,differences between toxins,doses,and injection tech-niques.Clinical results were promising,with all 8 studies reporting good results.All authors used BoNT type A(BoNT-A),either onabotulinum or abobotulinum toxin A.Response rates were variable,with full-response percentages of 32%-60%.As proven by the full-response rates of 50%,repeated injections are as safe and effective as first injections.Only a few cases of urinary tract infection,transient urinary retention,and hematuria have been reported,with no major local or systemic adverse effects.Despite these limitations,evidence encourages and supports BoNT-A use as a safe and effective treatment modality for refractory idiopathic OAB in pediatric set-tings,regardless of dosage and target toxin.To the best of our knowledge,this is the first systematic review of the use of intravesical BoNT-A for idiopathic OAB treatment in children.

Relationship between urodynamic patterns and lower urinary tract symptoms in Chinese women with a non-neurogenic bladder

Objective:To investigate the urodynamic study(UDS)patterns,obstruction status,continence status,and their correlations among neurologically intact women with lower urinary tract symptoms(LUTS)through an epidemiological and logistic regression analyses.Methods:We retrospectively analyzed the UDS data of 3265 neurologically intact women with LUTS(2002e2014).Five UDS patterns were identified:normo-active detrusor/sphincter(NA,or DSI,detrusor/sphincter intact),idiopathic detrusor overactivity(IDO),idiopathic sphincter overactivity(ISO),IDO+ISO,and detrusor underactivity(DUA).Analyses of UDS pattern distribution and stratification were performed(based on a modification of the European Urological Association-Madersbacher classification system),and their correlations with bladder outlet obstruction(BOO)and stress urinary incontinence(SUI)status were evaluated via logistic regression analysis.Results:NA,IDO,IDO+ISO,ISO,and DUA were noted in 927(28.4%),678(20.8%),320(9.8%),689(21.1%),and 651(19.9%)cases,respectively.Moreover,storage,storage+voiding,and voiding symptoms were noted in 62.4%,21.1%,and 16.5% cases,respectively,whereas BOO and SUI were observed in 12.1%and 29.0%cases,respectively.The risk factors for BOO included NA,IDO,ISO,and IDO+ISO,whereas the protective factors against BOO included storage symptoms,SUI,storage+voiding symptoms,and complaint duration within 1e12 months.NA was the only risk factor for SUI,whereas BOO,storage+voiding symptoms,IDO,and storage symptoms were protective factors for SUI.Conclusion:Five UDS patterns were identified among neurologically intact women with LUTS.Functional abnormalities of the detrusor and/or sphincter were the main causes of LUTS,and were correlated with the BOO or SUI status.Thus,the UDS pattern can provide additional information regarding the risk factors for BOO or SUI status,as compared to symptomatic typing.

Effect of phosphodiesterase inhibitors in the bladder

Many aging men will experience lower urinary tract symptoms(LUTS).Phosphodiesterase type 5(PDE5)inhibitors have shown promise in treating LUTS in these patients.PDE5 inhibitors mediate their effects through several pathways including cAMP,NO/cGMP,Kchannel modulated pathways,and the L-cysteine/H2S pathway.PDE5 inhibitors exert their effect in muscle cells,nerve fibers,and interstitial cells(ICs).The use of PDE5 inhibitors led to improvement in LUTS.This included urodynamic parameters.PDE5 inhibitors may play a significant role in LUTS due to their effect on the bladder rather than the prostate.

The Aging Bladder in Females Evaluated by Urodynamics

Aim: To determine whether bladder functions deteriorate with age. Methods: Data contained in electronic medical record (INFOMED?) were used in this institutional retrospective review. Analysis was done on the urodynamic studies in women over 18 years old conducted between May 2011 and November 2015. Patients with previous history of pelvic surgery or radiotherapy, neurological disease, vaginal prolapse greater than grade I, congenital urogenital malformations, urinary obstructive disease, diabetes, or the use of any medication that could interfere with bladder function were excluded from the analysis. The urodynamic parameters analyzed were the Maximum Cystometric Capacity (MCC), Voiding Volume (VV), Maximum Flow (Qmax), Bladder Compliance (BC), Detrusor Pressure at Maximum Flow (PdetQmax), Bladder Contractility Index (BCI), Bladder Voiding Efficiency (BVE) and Post-Void Residual Urine Volume (PVR). Patients were further stratified in five groups according to age (A—18 to 40;B—41 to 50;C—51 to 60;D—61 to 70;E—over 70 years old). Results: Out of 3103 urodynamic studies analyzed, 719 were eligible for the study. The average age of patients was 49.3 (+13.2) years old and in all evaluated parameters, statistically significant correlation between age and decline of bladder function was obtained (p Conclusions: This study showed a decline in bladder storage function (reduction in MCC and BC) and in bladder emptying function (reduction in Qmax, PdetQmax, VV, BCI and BVE with an increase in PVR) with age.

Expression of Large Conductance, Voltage- and Ca²⁺-Activated K⁺(BK) Channels in Human Urinary Bladder: Alteration of Subunit Expression Profile in Association with Bladder Outlet Obstruction

Purpose: Large conductance, voltage- and Ca2+-activated K+ (BK) channel is thought to have a central role to regulate urinary bladder smooth muscle functions, and its dysfunction may lead to increase of urination frequency and overactive bladder. The present study aims to investigate the expression pattern of BK channel subunits in the human urinary bladder, and how it changes in association with bladder outlet obstruction (BOO). Materials and Methods: Human bladders were obtained from 7 controls without prostatic enlargement and lower urinary tract symptoms and 4 BPH patients with clinically diagnosed overactive bladder who were verified by the International Prostate Symptom Score (IPSS) and prostate volume. The expression and location of BK channel protein complex was examined using immunohistochemistry with affinity-purified anti-BKα antibodies. A real-time RT-PCR was used to quantify the expression of each BK channel subunit (α and β1 - 4) gene in the mucosal and muscle layers of human urinary bladder. Results: Immunohistochemical staining for BK-α protein complex was localized in the muscle and submucosal regions of urinary bladder. RT-PCR analysis revealed the presence of α-, β1-, and β4-subunit genes of BK channel in the mucosal layer, α- and β1-subunit in the muscle layer. The expressions of α- and β1-subunit genes in the muscle (α: p = 0.0003, β1: p = 0.0003) and mucosal (α: p = 0.03, β1: p = 0.02) layers significantly decreased in BOO bladders compared with controls. The expression levels of α- and β1-subunit in mucosal layer were statistically correlated with storage score of IPSS (α;r = 0.84, p = 0.002, β1;r = 0.84, p = 0.002), and so were in muscle layer (α;r = 0.934, p 0.0001, β1;r = 0.917, p = 0.00018). Conclusions: BK channels, which are mainly composed of α- and β1-subunits, are expressed in both the mucosal and muscle layers of human urinary bladder. Decreased expression of BK channel in BOO might be implicated in the mechanisms underlying the development of overactive bladder.