Search Results (143)

Background and Objectives: Lower urinary tract symptoms (LUTS) are highly prevalent among aging men and have traditionally been attributed primarily to benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO). However, growing evidence suggests that bladder-related mechanisms play a critical and often underrecognized role. This review aims to summarize current evidence on the contribution of the aging bladder to LUTS pathophysiology and to explore the therapeutic implications in men with BPH. Materials and Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for studies published between January 2010 and April 2025. Search terms included combinations of “aging bladder”, “detrusor dysfunction”, “LUTS”, “BPH”, “bladder outlet obstruction”, “ischemia”, “overactive bladder”, and “detrusor underactivity”. Eligible studies included narrative reviews, systematic reviews, meta-analyses, clinical studies, and translational research addressing bladder aging and its clinical implications. A narrative synthesis approach was used due to heterogeneity in study design and outcomes. Results: A total of 43 studies were included in the qualitative synthesis. The evidence indicates that LUTS in older men result from multifactorial processes involving not only prostatic enlargement but also bladder dysfunction. Aging-associated changes include detrusor remodeling, impaired compliance, neural alterations, and vascular insufficiency, particularly chronic ischemia and oxidative stress. These mechanisms contribute to both detrusor overactivity and underactivity, providing a unifying framework for storage and voiding symptoms. Importantly, the severity of LUTS does not consistently correlate with prostate size or degree of obstruction. Conclusions: LUTS in aging men should be considered a complex condition involving both bladder and outlet factors. A bladder-centered perspective may improve patient stratification and therapeutic outcomes. Integrating bladder-targeted therapies with conventional BPH management supports a more personalized and effective approach to care. Full article

Botulinum toxin type A (BoNT/A) injection into the bladder wall is a milestone in the treatment of urinary incontinence in patients with neurogenic detrusor overactivity (NDOi) or overactive bladder syndrome (OABi) who are refractory to or unable to tolerate oral or transdermal therapies. However, the efficacy of BoNT/A is hampered by the low long-term adherence of patients to a treatment that requires repeated bladder injections under cystoscopy control. The discontinuation is particularly evident among incontinent patients with spontaneous voluntary voiding, regardless of whether the cause is NDOi or OABi, although clearly more marked among the latter group. In addition to the bother and pain associated with repeated cystoscopies, these patients show low tolerance to the high incidence of urinary tract infections (UTIs) and transient urinary retention, the two most common adverse events. Fewer injection points may render treatments less painful, apparently without reducing efficacy, but will not avoid the need for repeated cystoscopies, and no studies have demonstrated that such modification increases adherence. Eventually, accessing the bladder wall for BoNT/A administration via a transabdominal approach, under real-time ultrasound guidance, may overcome trans-urethral limitations, but the technique’s reproducibility remains unknown. An intensive investigation is ongoing to identify aids that facilitate the passage of the large, fragile BoNT/A molecule across the urothelium to reach the bladder nerves without injections. Electromotive Drug Administration (EMDA) of BoNT/A demonstrated efficacy and safety over a 6-year follow-up in NDOi patients at a single center, but the results were not reproduced at other institutions. The application of shock waves to the bladder using shock waves generated by Extracorporeal Shock Wave Lithotripsy (ESWL) machines to tear the urothelium and facilitate the passage of BoNT/A instilled in the bladder is ingenious, but the experience is very limited. Dimethyl sulfoxide, liposomes, and thermal-reversal hydrogel to deliver the toxin failed in pilot trials. BoNT/A in nano-formulations has high heat stability, resistance to pH changes, and to enzymatic degradation. Extended efficacy in dermal and intramuscular pilot applications is promising but needs to be replicated in the bladder. Full article

Objectives: To characterize urodynamic findings after lower-level spinal cord injury (LSCI) and to evaluate a new pressure-based classification framework—the bladder–sphincter dyscoordination syndrome (BSDS)—for describing voiding patterns. We also introduce a descriptive “neurogenic bladder outlet obstruction” (NBOO) phenotype for straining-dependent voiding difficulty. Methods: We retrospectively analyzed the first urodynamic studies (December 2020–August 2024) in 81 men with LSCI (injury at T10 or below). Key urodynamic measures included detrusor and intravesical pressures during filling and voiding, bladder volumes (first desire to void and capacity), compliance, maximum flow rate (Q_max), post-void residual (PVR), voiding efficiency, and the ratio of detrusor to abdominal pressure rise (ΔPdet/ΔPabd). We compared cases with detrusor overactivity (DO) versus those without DO. Among those with voiding discoordination, we distinguished classical detrusor–sphincter dyssynergia (DSD) from a proposed NBOO phenotype (characterized by abdominal straining pressure ≥ 40 cmH₂O, detrusor pressure < 20 cmH₂O, incomplete emptying, and no anatomic obstruction). We further classified discoordination cases using the BSDS framework into four subtypes—dual high-pressure (DHP), detrusor-muscle predominant (DMP), dual low-pressure (DLP), and abdominal-pressure predominant (APP)—based on reference pressure thresholds (detrusor 20 cmH₂O; abdominal 40 cmH₂O). Results: Patients with DO (43.2%) showed significantly higher detrusor pressures during filling (at first desire to void and at capacity) and a lower first desire volume than non-DO patients, while maximum capacity was similar (p = 0.105). During voiding, DO cases had lower PVR and higher emptying rates, although the detrusor-vs-abdominal pressure contribution (ΔPdet/ΔPabd) was comparable between groups. Among 63 patients with voiding discoordination, 32 (50.8%) met NBOO criteria; these NBOO cases exhibited lower detrusor and intravesical voiding pressures but worse emptying (higher PVR) compared to classical DSD cases. Overall, 76 of 81 patients (93.8%) fit within the BSDS classification—distributed as 22 DHP, 13 DMP, 15 DLP, and 26 APP patterns. Conclusions: The BSDS framework (and the NBOO descriptor when conventional indices cannot be applied) offers a novel way to describe voiding patterns after LSCI. It links urodynamic observations to potential management strategies (by identifying whether the bladder or outlet is the primary issue). Prospective studies are needed to validate this framework against outcomes such as upper tract integrity, continence, and dependence on catheterization. Full article

Background: Severe lower urinary tract dysfunction (LUTD) in neurologically and anatomically normal children is uncommon and frequently underdiagnosed. When severe, functional voiding disorders may closely mimic obstructive or reflux pathology, leading to diagnostic errors, unnecessary invasive procedures, and potential risk to the upper urinary tract. Case presentation: We present three pediatric cases (aged 3–10 years) referred for recurrent febrile urinary tract infections, incontinence, or acute urinary retention in the absence of neurological or structural abnormalities. Urodynamic evaluation identified three distinct severe functional phenotypes: detrusor overactivity with reduced bladder capacity, poor compliance with detrusor–sphincter dyssynergia and secondary high-grade vesicoureteral reflux (Hinman syndrome), and detrusor underactivity with significant post-void residual volumes. All patients demonstrated marked bladder wall remodeling on cystoscopy, including trabeculation and pseudopolypoid mucosal changes. Case discussion: Despite similar clinical severity, the cases illustrated substantial functional heterogeneity and differing risks of upper urinary tract involvement. Urodynamic phenotyping proved central to diagnosis, differentiation from structural disease, and treatment planning. Multimodal conservative management—including urotherapy, pelvic floor biofeedback, targeted pharmacologic therapy, and, when indicated, clean intermittent catheterization or antibiotic prophylaxis—led to resolution of recurrent infections and meaningful improvement in bladder function during medium-term follow-up, although symptom recurrence occurred in one patient after treatment withdrawal. Conclusions: These cases highlight the heterogeneity and potential reversibility of severe functional LUTD in otherwise healthy children. Early functional recognition based on urodynamic assessment is essential to avoid misdiagnosis, prevent unnecessary surgical intervention, and protect renal function. Conservative, function-oriented management remains the cornerstone of effective treatment. The findings are discussed in the context of the existing literature on severe non-neurogenic LUTD and Hinman syndrome. Full article

Older adults with multiple diseases are likely to be prescribed multiple medications including anticholinergic agents, which are frequently prescribed to manage conditions such as overactive bladder and chronic obstructive pulmonary disease and Parkinson’s disease. Overactive bladder (OAB) has been the subject of increased disease awareness and is a common and significant cause of reduced quality of life, particularly in the elderly. The selective β₃ adrenoceptor agonist, mirabegron was developed for the pharmacological treatment of OAB. Mirabegron has been shown to exert off-target effects on various functional proteins such as muscarinic receptors in rat tissues. This agent may relax the detrusor muscle by activating β₃ adrenoceptors and also antagonizing muscarinic receptors. Mirabegron and antimuscarinics exerted additive effects on muscarinic receptor binding and relaxant responses of cholinergic contractions of the detrusor muscle. Mirabegron excreted in human urine appears to directly attenuate muscarinic receptor-mediated functions in the bladder. Combination therapy of mirabegron and solifenacin in patients with OAB may enhance not only their therapeutic effects on OAB, but also increase the risk of anticholinergic adverse effects. Therefore, the safety of concomitant use of mirabegron and other drugs such as antimuscarinics for elderly patients needs to be carefully considered. Full article

Conflicting data exist regarding the effect of intradetrusor BoNT/A on the incidence of urinary tract infections (UTIs) in patients with neurogenic detrusor overactivity (NDO), contrary to the increase in UTIs noted in patients with idiopathic OAB. Associations between UTIs, chronic inflammation, and bladder overactivity are acknowledged, albeit not fully understood. Chronic bladder inflammation is common in both NDO and OAB patients, and both animal and human studies suggest a beneficial effect of BoNT/A on both urinary and systemic levels of inflammatory markers. To explore whether intradetrusor BoNT/A injections affect the background for the incidence of UTIs in humans, we investigated in parallel the effect of intradetrusor BoNT/A on the incidence of UTIs and on the urine mRNA levels of urinary pathogen-detecting Toll-like receptors TLR2, TLR4, and TLR5 and of factors acting as intermediates of immune response and promoters of inflammatory reactions (IL1β, IL6, TNFα, and PGE₂). For this purpose, we recruited 22 patients with NDO-associated incontinence who received at least one bladder BoNT/A injection. Urine specimens for the study of UTIs were obtained before the procedure and at routine urodynamic follow-ups at 4–6 weeks, 6 and 12 months post-BoNT/A, and at clinical relapse, while urine specimens for the study of biomarkers were collected at the time of BoNT/A injection and at the abovementioned follow-ups thereafter. Urine specimens from 10 adult healthy volunteers with no OAB symptoms served as the control group in the biomarker study. The genes of interest in the urine were studied by RNA isolation, reverse transcription, and real-time PCR. The urine mRNAs of all biomarkers tested appeared to be upregulated in the patients’ samples compared with the controls, albeit only TLR2 and TLR5 mRNA increases were statistically significant. A progressive downregulation of TLR2, TLR5, IL1β, and IL6 urine mRNAs was noted at one and six months post-BoNT/A. TNFα and PGE₂ mRNAs showed a transient increase at one month post-BoNT/A followed by a dramatic drop at the six months’ follow-up. A similar trend for progressive decline was also noticed in the prevalence of both positive urine cultures and symptomatic UTIs in the same timepoints and additionally at 12 months post-treatment in patients who still benefited from the BoNT/A treatment. Upon clinical relapse, the mRNA levels of PGE₂, IL1β, and IL6 increased in parallel with an increase in the prevalence of UTIs, while the levels of TLRs and TNF-α did not follow the same trend. In summary, intradetrusor BoNT/A injections achieved significant decreases in the urine mRNA levels of pathogen-detecting TLRs, immune response, and inflammation mediator cytokines and PGE₂ in our cohort of patients with NDO-associated incontinence. In parallel, decreases were noted in both the incidence of symptomatic UTIs and rates of positive urine cultures. At the time of clinical relapse, the markers of inflammation and immune response, but not TLRs, were upregulated in parallel with the increased incidence of UTIs, suggesting that the studied genes PGE₂, IL1β, and IL6 could be further explored as potential biomarkers for inflammation/immune response and UTIs in the neurogenic population. Full article

Background/Objectives: Neurogenic detrusor overactivity (NDO), caused by spinal cord injury or multiple sclerosis, is marked by involuntary bladder contractions and reduced urine volume. Current therapy requires frequent catheterization with oxybutynin hydrochloride. This work investigates a novel in situ forming implant (ISFI) with PLGA as a sustained-release formulation for the urinary bladder by quantifying drug release, polymer degradation, and solvent release in vitro. Methods/Results: Various formulation parameters were investigated, of which the drug load and PLGA termination were found to have the highest impact on drug release and polymer degradation. An increase in drug load from 1.5% to 7.5% for implants with the ester-terminated PLGA enhanced the degradation from 0% to around 20% after 7 d. Oxybutynin base catalyzed the polymer degradation, as implants with PLGA 502 and 15% drug load exhibited a degradation of 33% compared to 0% for 1.5% drug load. In the case of 1.5% drug load, the degradation could be increased by the use of an acid-terminated PLGA, compared to an ester-terminated. Conclusion: In summary, the feasibility of a biodegradable ISFI for NDO patients was shown, which could allow a single administration up to approx. one week, improving the quality of life for NDO patients. Additionally, this work provided insight to which formulation parameters can help to parallel drug release and polymer degradation. Full article

Background/Objectives: Bulkamid^® (Axonics, Irvine, CA, USA) is a non-particulate polyacrylamide hydrogel used in the treatment of urinary incontinence. While its effectiveness is well-documented in female stress urinary incontinence (SUI), there is limited data on its role in male stress urinary incontinence, particularly post-prostatectomy incontinence (PPI). This study evaluates the efficacy of Bulkamid as a primary or adjunctive treatment for male PPI. Methods: A retrospective chart review was conducted on male patients who developed PPI and underwent Bulkamid injections between 2016 and 2021. Data collected included pre- and post-procedure pad usage, the volume of Bulkamid injected, prior and subsequent incontinence treatments, and patient-reported satisfaction. Bulkamid was injected transurethrally in four quadrants near the vesicourethral anastomosis using a rigid cystoscope. Results: Twenty-one men with a history of radical prostatectomy (six open and fifteen robotic), including four who received adjuvant radiotherapy, were included. Fifteen underwent Bulkamid injection as a primary treatment, with five (33%) requiring repeat injections due to initial improvement. Eight (54%) subsequently underwent an AdVance XP^® sling placement, while two (13%) required no further treatment. Six patients received Bulkamid as an adjunct to prior incontinence surgery, with 80% of post-sling patients reporting improved continence. Bulkamid was less effective in men with detrusor overactivity or prior radiation. Conclusions: Bulkamid demonstrated a higher success rate as an adjunct to the AdVance XP sling, with 80% of men experiencing improved continence. As a primary treatment for PPI, success was modest, with only 33% achieving improvement, often requiring repeat injections or conversion to a sling. Bulkamid presents a low-risk option for select male PPI patients, particularly those with prior sling placement, but durability and long-term effectiveness remain concerns. Full article

Bladder dysfunction, particularly overactive bladder (OAB), is increasingly recognized as a clinical concern in patients with sickle cell disease (SCD), yet its pathophysiological mechanisms remain poorly understood. This study investigated the relationship between oxidative stress, inflammation, and bladder dysfunction in the Townes transgenic SCD mouse model. Cystometric analysis revealed that SCD mice exhibit an OAB phenotype, characterized by increased frequencies of voiding and non-voiding contractions and reduced bladder compliance. In vitro functional assays demonstrated detrusor hypocontractility in SCD mice, associated with a significant reduction in carbachol- and EFS-induced contractions and downregulation of muscarinic M3 receptor expression. Purinergic signaling and calcium-dependent contractility remained preserved. Molecular analyses showed increased mRNA expression of NOX-2 and IL-1β, and elevated protein levels of 3-nitrotyrosine and myeloperoxidase (MPO) activity, indicating redox imbalance and chronic inflammation in bladder tissue. Together, these changes suggest that oxidative and nitrosative stress, combined with inflammation, contribute to bladder remodeling and dysfunction in SCD. This is the first study to characterize bladder alterations in Townes SCD mice, establishing this model as a valuable tool for investigating lower urinary tract complications in SCD. Our findings provide mechanistic insight into the genitourinary manifestations of SCD and identify redox and inflammatory pathways as potential therapeutic targets for bladder dysfunction in affected individuals. Full article

Purpose: This study aimed to identify the predictive factors for successful or failed treatment outcomes following intravesical injection of botulinum toxin A (BoNT-A) through an analysis of baseline video urodynamic characteristics and parameters. Methods: This study retrospectively analyzed the therapeutic outcomes of intravesical BoNT-A injection in patients who had an overactive bladder (OAB), who were diagnosed with detrusor overactivity (DO), and who had been refractory to OAB medications or intolerant of the adverse events associated with them. Treatment outcomes were classified as successful, improved, or failed according to the patients’ subjective report of improvement in OAB symptoms at three months post-injection. The patients were split into male and female cohorts and neurogenic or non-neurogenic DO for data analysis. The video urodynamic study characteristics and parameters were compared across the successful, improved, and failed subgroups. Results: This study included 571 patients who received intravesical BoNT-A injections for treating their OAB and urodynamic DO, of which 272 were men and 299 were women. The treatment outcome of BoNT-A injection was successful in 55.7%, improved in 27.8%, and failed in 16.5% of the patients. Patients with urodynamic detrusor underactivity (DU) and neurogenic DO due to diseases of the central nervous system did not usually achieve a successful outcome. The following factors predicted successful treatment outcomes following BoNT-A injection: lower baseline detrusor pressure, higher maximum flow rate (Qmax), larger voided volume, and smaller post-void residual (PVR) in men; larger voided volume and smaller PVR in women. Conclusions: The therapeutic success of intravesical BoNT-A injection for treating refractory OAB can be predicted by lower Pdet, higher Qmax, larger voided volume, and smaller PVR in men and by higher Qmax and smaller PVR in women. Patients with neurogenic DO and DU usually have unsuccessful treatment outcomes. Full article

Introduction: Overactive bladder (OAB) and urinary incontinence (UI) are prevalent, particularly in older adults, and affect quality of life. OAB involves urgency, frequency, nocturia, and urgency incontinence, often linked to involuntary detrusor contractions. Treatment guidelines recommend a stepwise approach, starting with pelvic floor muscle training (PFMT), followed by pharmacological or minimally invasive therapies, such as neuromodulation. However, the combined effects of PFMT and neuromodulation have not been well established. This study aimed to evaluate the impact of combining pelvic floor exercises with neuromodulation versus PFMT with sham neuromodulation or standard physiotherapy after a 12-week intervention in individuals with OAB and UI. Methods/Materials: A double-blind, randomized controlled trial was designed with three groups: PFMT + neuromodulation, PFMT + sham, and conventional physiotherapy (control) in a 1:1:1 ratio. This study followed the CONSORT guidelines and was registered at ClinicalTrials.gov (NCT06783374). The sample size was calculated using GPower^® software, assuming a Cohen’s effect size of 1.04, a power of 0.80, an alpha of 0.05, and a 15% dropout rate, totaling 63 participants (21 per group). Participants attended 24 sessions over 12 weeks (2 sessions per week). The interventions were based on previously validated protocols. Outcomes: The primary outcomes included health-related quality of life, pelvic floor muscle function, pain, adherence, and general health. The secondary outcomes included Incontinence Quality of Life questionnaire, 3-day bladder diary, International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form, kinesiophobia, and electromyographic data. Full article

Background/Objectives: Overactive bladder (OAB), common in elderly women, involves urgency, frequency, and nocturia, with complex phenotypes. The use of neurotrophins as non-invasive urinary biomarkers has been previously explored. The objective of this study was to assess the diagnostic and therapeutic utility of urinary biomarkers in a Canadian population of aging female OAB patients. Methods: We conducted a single-center prospective study of aging female patients diagnosed with OAB and age-matched healthy controls, where we conducted pre- and post-treatment assessments using a combination of clinical questionnaires, voiding diaries, and urinary biomarkers nerve growth factor (NGF), proform of NGF (proNGF), brain-derived neurotrophic factor (BDNF), proform of BDNF (proBDNF), and neurotrophin receptor p75 extracellular domain (p75^ECD)) quantified using ELISA. Baseline and post-treatment urinary biomarker levels in OAB patients were compared with those of controls. Results: OAB patients and controls at baseline displayed significant differences in neurotrophin levels and in their ratios of mature/precursors. In the post-treatment OAB cohort, only NGF and proNGF exhibited significant improvement correlating with clinical symptom relief. Biomarkers in non-responders remained unchanged, suggesting heterogeneity in therapeutic response. Conclusions: Urinary neurotrophins show promise as non-invasive diagnostic markers of OAB and monitoring treatment response in aging female patients. While this study focused on patients broadly diagnosed with OAB, future research should aim to classify OAB subtypes—such as those based on urodynamic studies or underlying pathophysiology—to better understand how urinary neurotrophins can differentiate between mechanisms like detrusor overactivity, detrusor underactivity, or bladder outlet obstruction. This will enhance their relevance in guiding personalized treatment strategies and predicting outcomes. Full article

Background/Objectives: Intradetrusor botulinum toxin injection is a well-established third-line therapy for patients with refractory overactive bladder (OAB) and detrusor overactivity (DO). Botulinum toxin type A (BoNT-A) is most commonly used due to its prolonged therapeutic duration. We aimed to evaluate the effectiveness of intradetrusor BoNT-A injection therapy in managing refractory OAB by performing a urodynamic study (UDS). Methods: The patients were prospectively enrolled between February 2020 and March 2021. The patients received treatment regimens comprising behavioral modification therapy, pelvic floor muscle physiotherapy, and/or OAB medications for at least three months. The UDS procedure was carried out by a single examiner, in accordance with the International Continence Society standards for good urodynamic practice. A total of 100 units of BoNT-A was dissolved in 10 mL of saline, and 0.5 mL (5 units) was injected at 20 sites on the posterior wall of the bladder. The primary endpoint was the change in DO, which was measured using the UDS from the baseline to two months after treatment with BoNT-A. Results: Prior to treatment initiation, DO was observed in all the patients during the UDS. The occurrence of DO during the filling phase demonstrated a significant decrease following treatment, with DO no longer identified in 27.3% of the patients. The first sensation of bladder filling, maximum cystometric capacity, DO, and terminal DO all demonstrated significant improvement after intradetrusor BoNT-A injection, based on the UDS. The OAB symptom scores also significantly decreased after BoNT-A therapy. Conclusions: The present study demonstrated that intradetrusor BoNT-A injection significantly improved symptoms in patients with OAB who had been unresponsive to various treatments. This study also demonstrated the usefulness of performing a UDS before and after treatment to prove the efficacy of BoNT-A. Full article

Background: Mixed urinary incontinence (MUI), particularly the urge-predominant subtype, involves both stress urinary incontinence (SUI) and urge urinary incontinence (UUI), posing a therapeutic challenge. Duloxetine, a serotonin–norepinephrine reuptake inhibitor (SNRI), enhances urethral tone, while tolterodine, an antimuscarinic agent, reduces detrusor overactivity. Their combination may offer synergistic benefits. Aim: The aim of this study was to evaluate the efficacy of duloxetine and tolterodine combination therapy in urge-predominant MUI and identify factors influencing treatment success. Method: A retrospective study was conducted on 106 patients (mean age: 56.45 years) with urge-predominant MUI treated with duloxetine (40 mg twice daily) and tolterodine (4 mg once daily) for 12 weeks. Treatment outcomes were evaluated using the overactive bladder symptom score (OABSS), International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), 24 h pad test, and Clinical Global Impression Scale (CGI). Univariate and multivariate regression analyses were performed to determine predictors of success. Results: Significant improvements were observed: OABSS decreased from 11.08 to 6.95, ICIQ-SF decreased from 15.69 to 8.84, and pad use decreased from 3.58 to 0.73/day (all p 0.0001). Bladder capacity increased from 315.09 mL to 436.32 mL. Baseline ICIQ-SF scores were independent predictors of success (odds ratio [OR] = 2.919, p = 0.001). Patient satisfaction reached 77.4%, with mild side effects (constipation and dizziness) in 14 patients. Conclusions: Duloxetine and tolterodine combination therapy significantly improved symptoms and quality of life in urge-predominant MUI. Baseline ICIQ-SF scores may predict treatment success. Further prospective studies are needed. Full article