Urethrogenic Overactive Bladder: A Systematic Review of Pathophysiological Mechanisms and Clinical Implications

Urethrogenic Overactive Bladder: A Systematic Review of Pathophysiological Mechanisms and Clinical Implications | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Urethrogenic Overactive Bladder: A Systematic Review of Pathophysiological Mechanisms and Clinical Implications Eleonora Rosato, Sofia Maliziola, Livia Mollo, Petra Vogrig, Giuseppe Farullo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9152026/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Purpose While Overactive Bladder (OAB) is traditionally viewed as a detrusor-centric dysfunction, emerging evidence suggests the urethra plays a critical role in its pathogenesis. This review aims to evaluate the contribution of urethral mechanisms—including pressure variations, sensory thresholds, and morphological changes—to OAB symptoms and to explore the efficacy of urethra-targeted interventions. Methods A comprehensive review of clinical studies was conducted, analysing urodynamic data, Current Perception Thresholds (CPT), and magnetic resonance imaging (MRI) findings across cohorts of patients with OAB, mixed urinary incontinence (MUI), and asymptomatic controls. Therapeutic outcomes from sacral neuromodulation (SNM), urethral calibration, and micro-radiofrequency (RF) therapy were also synthesized. Results Patients with OAB and MUI frequently exhibit significant ‘urethral instability’ and pressure fluctuations compared to those with pure SUI. Sensory testing demonstrated that OAB is associated with altered urethral perception thresholds, suggesting a state of hypersensitivity or neural dysfunction in the lower urinary tract. Furthermore, imaging data identified distinct structural and morphological differences in the urethral sphincter and surrounding musculature of symptomatic patients. Finally, clinical outcomes indicate that interventions specifically targeting the urethra—ranging from mechanical calibration to neuromodulation and thermal therapies—result in a meaningful reduction of urgency episodes and an overall improvement in quality of life. Conclusions The urethra acts as a dynamic modulator of the micturition reflex rather than a passive conduit. Urethral sensory and mechanical dysfunctions are key components of OAB, and therapies targeting these urethral pathways offer promising alternatives for patients who do not respond to traditional detrusor-focused treatments. overactive bladder urethra urethrogenic overactive bladder detrusor overactivity urinary incontinence urgency Figures Figure 1 Figure 2 Figure 3 1. Introduction Overactive bladder (OAB) was defined by the International Continence Society (ICS) as a storage symptom syndrome characterised by ‘urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia in the absence of urinary tract infections or other pathology’ 1 . In approximately 50% of cases, OAB is associated with detrusor overactivity (DO) observed during invasive urodynamic studies (iUDS) 2 . However, DO and OAB should not be considered synonymous and multiple mechanisms—linked to the urothelium, suburothelium, urethra, and central nervous system (CNS)—are believed to contribute to the pathogenesis of OAB 2 , 3 . Among these, the urethrogenic hypothesis proposes that urgency originates in the urethra. In the early 20th century, Barrington and other authors described various micturition reflexes in animal models 4 . They defined that micturition reflexes could be evoked by running water through the urethra or by the entry of urine into its proximal part. In patients with stress urinary incontinence (SUI), stimulation of urethral afferents may induce or exacerbate DO. In this case, OAB might seem to originate from the bladder neck 5 . Other potential urethral contributors to OAB include diminished urethral tone—often related to oestrogen deficiency in females—and urethral pressure variations during bladder filling (urethral instability) 6 . In patients with pelvic organ prolapse (POP), a vagina, incapable of supporting the bladder neck/proximal urethra stretches receptor and activates prematurely the micturition reflex 7 . The current European Association of Urology (EAU) Guidelines recommend a stepwise approach to OAB treatment, progressing from behavioural therapies to pharmacological interventions and ultimately surgical options 8 , 9 . However, phenotyping OAB or DO may lead to more individualized and effective management strategies. Recently, Peyronnet et al proposed many possible OAB phenotypes according to pathophysiological factors or to urodynamic demonstration of DO 3 . Furthermore, at the ICI-RS 2023 meeting, Finazzi Agrò et al. emphasised the importance of adopting a comprehensive and personalised approach to phenotyping patients with lower urinary tract symptoms (LUTS), including both OAB and underactive bladder 10 , 11 . According to the concept of a future tailored approach to the treatment of OAB, this systematic review aims to summarise the current evidence on the pathophysiology, diagnostic considerations, and therapeutic approaches related to urethrogenic OAB. 2. Methods The present SR was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement 12 . 2.1. Search strategy After registering the protocol with PROSPERO (registration number CRD420250548418), we conducted a comprehensive literature search in PubMed, Embase, and Cochrane CENTRAL, including peer-reviewed studies published between January 2003 and December 2025. The search strategy employed both Medical Subject Headings (MeSH) and free-text terms. Full details of the search protocol are provided in Supplementary File 1 . 2.2. Inclusion and exclusion criteria Two authors (SM and LM) independently screened all titles, abstracts, and full-text records against the eligibility criteria by collecting them in an Excel sheet. In case of any disagreement, a third author (ER) solved the divergence. No automation tools were used. For this systematic review, we included randomized controlled trials, cohort studies, and case-control studies enrolled both sex. We excluded case reports, surveys, expert opinions, editorials, abstracts, guidelines, review articles, and meta-analyses. Studies involving paediatric populations, neurological patients, or animal/cadaveric models were also excluded. Additionally, studies not addressing overactive bladder in relation to urethral physiology or pathophysiology were not considered. Patients affected by pure SUI were excluded while patients with urge urinary incontinence (UUI) or mixed incontinence (MUI) were considered. 2.3. Data collection process and data items We collected information on the authors, year of publication, and the institution where the study was conducted. The study design (retrospective, prospective, randomized controlled trial [RCT], or non-randomized controlled trial [NRCT]) was also recorded. For each included study, we extracted data on the number of participants, their age (mean ± standard deviation, range, and median), and sex distribution (male and female). Finally, we reported the study objectives and a summary of the main results. 2.4. Reporting bias assessment The risk of bias of each included study was assessed by two review authors working independently using the Cochrane Collaboration Risk of Bias Tool for Randomized Controlled Trials (Rob 2) and the Risk of Bias In Non-randomised Studies of Interventions Version 2 (ROBINS-IV 2) scale for randomized and non-randomized observational studies, respectively. 3. Results 3.1. Study inclusion A total of 292 publications were initially identified through database searches. Figure 1 illustrates the flow of information through the different phases of this systematic review, in accordance with PRISMA guidelines 12 . Ultimately, 18 manuscripts met the eligibility criteria and were included in the final analysis. 3.2. Study Characteristics Among included eighteen studies, 11 (61.1%) were prospective and 7 (38.9%) retrospective in design. The majority (83.3%, n = 15) obtained Institutional Review Board (IRB) approval, while 3 studies (16.7%) did not report ethical approval. The total population across all studies comprised 1,134 patients, with individual sample sizes ranging from 10 to 230. Female participants represented the vast majority (81.9%, n = 16 studies included only women), whereas 2 studies (18.1%) enrolled both sexes. The mean or median age of participants varied between 42 and 69 years. All details are reported in Table 1 and Table 2 . Table 1 – Characteristics of the included studies, providing an overview of study designs, participating institutions, ethical approval status, and patient demographics. Study Institution Design Institutional Review Board (IRB) Approval Number of patients Sex Age (years) Mattiasson et al., 2006 Lund University Hospital, Lund, Sweden Prospective No 87 F NA Futyma et al., 2015 University of Lublin, Lublin, Poland Retrospective Yes 208 F OAB Group 54.6 ± 14.57) MUI Group 58.03 ± 11.86 Rahmanou et al., 2011 St. Mary’s Hospital, Imperial College, London, UK Prospective Yes 17 F 50 (20–80) Cucchi et al., 2004 Policlinico S. Matteo, Pavia, Italy; Universita' di Trieste, Italy; Istituto di Medicina Fisica e Riabilitazione, Udine, Italy; Universita' di Pavia, Italy Retrospective No 40 F Group 2 51 ± 13 Group 2A 49 ± 15 Group 2B 52 ± 12 Kulseng-Hanssen et al., 2013 Bærum Hospital, Rud, Norway Vestfold Hospital, Tønsberg, Norway Retrospective No 100 F 51.5 Kirschner-Hermanns et al., 2017 University Hospital Friederich Wilhelms, University Bonn, Germany; The Federal State Institute of Public Health, The Nikiforov Russian Center of Emergency and Radiation Medicine, Saint-Petersburg, Russian Federation; Laborie, Mississauga, ON, Canada Prospective Yes 60 F OAB Group 60.2 ± 13.6 MUI Group 58.5 ± 14.4 Lowenstein et al., 2009 Loyola Medical Center, Chicago, Illinois;St. Luke’s Medical Center, Chicago, Illinois; Rambam Medical Center, Faculty of Medicine, Haifa, Israel Retrospective Yes 33 Both 60 (36–82) Kenton et al., 2007 Loyola University Medical Center, Maywood, Illinois Prospective Yes 13 F 62 ± 14 Ichiyanagi et al., 2017 Yamagata University; Yonezawa City Hospital,Yonezawa, Japan; Okitama General Hospital,Kawanishi town, Japan; Ishigooka Clinic, Yamagata, Japan Retrospective Yes 12 Both 69 (49–84) Wenzler et al., 2014 INS, Oakland University, CA Prospective Yes 10 F 58.9 (31–73) Vijaya et al., 2012 St. Mary’s Hospital, Imperial College, London, UK Prospective Yes 20 F 46 (36–68) Serati et al., 2014 Università dell’Insubria, Varese, Italy; IRCCS San Raffaele, Milano, Italy Prospective Yes 230 F Group 1 65 (54–77) Group 2 62 (52–81) Gleason et al., 2013 University of Alabama at Birmingham, Birmingham, AL, USA; Loyola University Medical Center, Chicago, IL, USA Prospective Yes 26 F 61 ± 13 Groenendijk et al., 2007 Leiden University, Leiden and Radboud University Nijmegen (JPFAH), Nijmegen, The Netherlands Prospective No 19 F 45.6 ± 7.7 (31–58) Wang et al., 2022 Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China College of Biomedical Engineering and Medical Imaging, Army Medical University, Chongqing, China Prospective Yes 11 F 42 ± 15.5 Chen et al., 2023 The Queens Medical Center, Honolulu, HI John A. Burns School of Medicine, University of Hawai‘i, Honolulu, HI Prospective Yes 88 F 64.48 ± 13.15 Tang et al., 2023 The First Aliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China, Nanjing, Jiangsu, China Center for Global Health, School of Public Health,Nanjing Medical University, Nanjing, Jiangsu, China Prospective Yes 46 Both 41.11 ± 14.23 Xu et al., 2022 Zhejiang Provincial People’s Hospital, Hangzhou, China,The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China Zhejiang-California International NanoSystems Institute, Hangzhou, China Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China Prospective Yes 114 Both 43.37 ± 12.57 Table 2 Summary of study objectives and clinical outcomes. Study N° of patients Objectives of the study Results Mattiasson et al., 2006 87 To investigate the urethral motor function in incontinent women UDS parameters in MUI (n = 46) vs. UUI (n = 21) patients MUP (cm H2O ): 58.6 ± 17.0 vs. 68.4 ± 25.3, p = ns MUCP (cm H2O ): 45.6 ± 18.0 vs. 62.7 ± 24.0, p = 0.006 FPL (mm): 29.2 ± 5.9 vs. 28.1 ± 5.5, p = ns All pressure falls provoked by squeeze (%): 62.2 vs. 57.1, p = ns Qmax (ml/sec): 30.1 ± 33.8 (range 5-175) vs. 19.5 ± 9.6 (range 2–40), p = ns Pdetmax (cm H2O ): 28.8 ± 14.2 vs. 36.5 ± 16.7, p = 0.04 Futyma et al., 2015 208 The study evaluated if uroflowmetry parameters can aid in diagnosing OAB using a new parameter, the flow index (FI, the ratio of average to maximum urine flow rate) proposed as a potential diagnostic marker UDS parameters between OAB Group (n = 66) vs. MUI Group (n = 142) FI: 0.45 (0.08) vs. 0.48 (0.11) DO: 12/66 (18.2%) vs 18/142 (12.3%) AFL: 9.75 (4.3–26.5) vs. 10.50 (4.1–34.8) MUF: 22.35 (10.3–63.6) vs. 23.75 (10.7–64.5) Rahmanou et al., 2011 17 To determine and compare reproducibility of UPP and MUCP in women with urodynamic USI without DO (Group 1) and USI with DO (Group 2) There were no significant differences between the groups in terms of age, parity, body mass index, or menopausal status. Group 2 exhibited greater intra-subject variability in all UPP parameters (MUCP, MUP, FUL) compared with Group 1. However, none of these parameters showed statistically significant differences between the two groups. Cucchi et al., 2004 40 To ascertain whether abdominal pressure transmission (APT) to the urethra would be affected by urgency in women with SUI (Group 1 = 40 patients) or MUI (Group 2 = 40 patients split in Group 2A and Group 2B for the ability to delay an urgent void at CMG for at least 2 minutes) Groups 2A vs 2B duration of urge symptoms 9 ± 7 vs. 7 ± 6 months. P-values were < 0.001for differences in both PTR ave and hMUP among Groups 1–2, 1-2A, and 2A-2B. Differences among Groups 1-2B were not statistically significant. Kulseng-Hanssen et al., 2013 28 To examine how often DO causes leakage during a stress test in women with mixed urinary incontinence MUI and if there are differences between patients with or without DO during the stress test (20 jumping jacks and three forceful coughs) 100% patients leaked during the stress test, 5% due to simultaneous stress test and DO, 87% due to the stress test only, and 8% during the stress test as well as due to DO before or after the stress test. Women with DO have a significantly higher Urgency Incontinence Index and 24-h pad-test leakage (p = 0.001 and p = 0.046). Kirschner-Hermanns et al., 2017 60 To study urethral pressure variations during the filling phase of pressure/flow studies in OAB patients compared with SUI and MUI group Characteristics of OAB Group (n = 29) vs. SUI Group (n = 19) vs. MUI Group (n = 31) Prevalence of urethral instability (%): 79.3% vs. 47.4% vs. 36.6% Post-menopausal rate (%): 79.3 vs. 84.2 vs.77.4 Mean Δ Pressure (cm H2O ): 36.5 vs. 14.9 vs. 19.3, p < 0.05 Maximum urethral closure pressure (cm H2O ): 202.1 vs. 114.5 vs. 89.0 Minimum urethral closure pressure (cm H2O ): 1.0 vs.3.0 vs.3.8 Functional Urethral Length (mm): 38.0 ± 7.9 vs. 33.9 ± 8.7 vs. 32.1 ± 6.6 AUC Urethral pressure curves: 1195.7 ± 985.6 vs. SUI 549.4 ± 273.0 vs. 429.3 ± 214.5 OAB Group with DO vs. OAB Group without DO Mean urethral pressure (cm H2O ): 85.5 ± 37.0 vs. 45.2 ± 30.65, p < 0.05 Lowenstein et al., 2009 33 To describe the temporal relationship between increases in bladder sensation and changes in detrusor and/or urethral pressures, and to explore quantitative relationships between the changes in detrusor pressures and changes in urgeometer level DO vs. DOI: no difference in change in sensation level (p > 0.5), no dominant temporal pattern (p = 0.84), no evidence that the change in sensation level was more likely to occur before, during, or after DO/DOI episodes UPP characteristic: the most common pattern seen was an increase in sensation level after a fall in urethral pressure, but no dominant pattern was seen. Kenton et al., 2007 13 To compare CPT in the urethra and bladder of women with idiopathic OAB to asymptomatic controls Women with UUI were significantly older (62 ± 14 vs. 44 ± 15, p < 0.0005) and more likely to be vaginally parous (92 and 51%, p = 0.007). Urethral CPT at 2,000, 250, and 5 Hz were significantly higher in women with UUI than controls, while bladder CPT were not different between groups (2,000 Hz: 1.15 (0.76–1.53) vs. 2.63 (1.31–5.39), p = 0.005; 250 Hz: 0.45 (0.33–0.56) vs. 1.39 (0.69–2.06), p < 0.0005; 5 Hz: 0.11 (0.7–0.24) vs. 1.14 (1.01–1.86), p < 0.0005). No statistically significant bladder findings. Ichiyanagi et al., 2017 12 To investigate associations between urethral sensation and UUI in patients with and without DO UDS parameters and urethral CPT of the patients with normal CMG (n = 11) vs. idiopathic DO (n = 12) First desire to void (mL): 85 (34–158) vs. 173 (5–230) MCC (mL): 403 (197–625) vs. 324 (28–511) Bladder compliance (mL/H2O): 104.7 (29.5–418.5) vs. 25.5 (0.4–191.4) Urethral CPT (mA): 2.8 (1.0–5.2) vs. 9.0 (2.0–28.0) Wenzler et al., 2014 10 To investigate if SNM affects perception thresholds of afferent sensory nerve pathways on bladder and urethra after 1 month OAB-q Score : 78.33 vs. 31.76 (p < 0.00001) OAB QoL : 30.32 vs. 73.39 (p = 0.022) CPT at 250 and 2000 Hz in the bladder: 335.75 mA +/- 358.036 (p = 0.033) Vijaya et al., 2012 20 To evaluate the effect of Tolterodine vs. placebo on urethra and bladder afferent nerves by evaluating the CPT changes (mA) Only in the tolterodine ER group (n = 10) there was a significantly CPT at 5 and 250 Hz for both urethral and bladder stimulation after 1 week of treatment Urethra CPT 5 Hz from 1.12 (1.05–1.27) to 1.30 (1.19–1.30), p-value 0.04 250 Hz from 1.43 (0.95–1.88) to 1.84 (1.61–1.99), p-value 0.01 Bladder CPT 5 Hz from 0.73 (0.29–1.01) to 2.96 (2.07–2.78), p-value 0.01 250 Hz from 1.45 (0.91–1.90) to 1.76 (1.06–2.33), p-value 0.01 Serati et al., 2014 230 To evaluate Solifenacin efficacy in patients with de novo OAB after TOT (Group 1, n = 110) vs naive women with OAB (Group 2, n = 120) Group 1 vs. Group 2 Median voided vol/micturition ml (IQR): 122 (67–142) vs 143 (123–187), (p < 0.0001) Median change urgency episodes/24h :1.1 vs 2.3, (p < 0.0001) Median change UUI episodes/24h: 0.2 vs 1.1, (p < 0.0001) Median micturitions/24 (%): 10 (6–15) vs 7, (5–12) (p < 0.0001) Median USS change: 1.5 vs.2.25, (p < 0.0001) PGI-I score ≤ 2 (%): 36 (32.7) vs. 85, (70.8) (p < 0.0001) Symptom severity at OAB-q SF: 28.50 vs. 40.25, (p < 0.0001) QoL at OAB-q SF:23.25 vs 34.50, (p < 0.0001) Gleason et al., 2013 26 To characterize the effect of SNM on urethral neuromuscular function in women with refractory OAB 20/26 (76.9%) women responded to SNM with a significant improvements in the UDI-6 and UIQ-7 (p < 0.001). Pre-SNM urethral sensation was not significantly different between responders and non-responders. CPT and CNE parameters did not significantly differ from baseline after 2 weeks. Groenendijk et al., 2007 19 To evaluate the predictive value of urethral instability and other urodynamic parameters on the efficacy of SNM 13/19 (68%) responded to SNM, 6/15 patients with UI were completely dry and 5/15 had more than a 50% decrease in leakage episodes. At 6 months (baseline vs. follow-up) n. leaks/24h 13 ± 10 vs. 6 ± 8, p = 0.001 Leakage severity 2.2 ± 0.68 vs. 1.5 ± 0.45, p = 0.019 n. pads/24h 8.4 ± 7.0 vs. 4.0 ± 6.2, p = 0.002 At 6 months (SNM device on vs. SMN device off) URI + DO: 4 vs. 8 URI, no DO: 5 vs. 7 No URI, DO: 1 vs. 0 No URI or DO: 7 vs. 2 At 6 months UDS parameters (baseline vs. follow-up) FSF bladder vol (ml): 98 ± 88 vs. 235 ± 159, p = 0.002 MCC (ml): 284 ± 108 vs. 346 ± 166, p = 0.061 Peak detrusor pressure (cm H2O ): 42 ± 33 vs. 25 ± 14, p = 0.028 Volume at peak bladder pressure (ml): 239 ± 140 vs. 317 ± 153, p = 0.041 Peak urethral pressure during cystometry (cm H2O ): 121 ± 42 vs. 113 ± 42, p = 0.15 Wang et al., 2022 11 To examine the 3D morphological changes of the urination and urinary continence anatomical structures in OAB patients (n = 11) compared with healthy volounteers (n = 9) in MRI scans MRI parameters in patients with (n = 11) and without (n = 9) OAB Thickness of bladder detrusor (mm): 3.1 ± 0.7 vs. 1.9 ± 0.3, p = 0.000 Volume of bladder detrusor (mm 3 ): 50,632.0 ± 19,724.7 vs. 23,386.6 ± 7826.3, p = 0.001 Thickness of main part of urethral sphincter (mm): 2.2 ± 0.5 vs. 2.7 ± 0.3, p = 0.018 Volume of main part of urethral sphincter (mm 3 ): 2558.6 ± 703.2 vs. 3267.3 ± 681.9, p = 0.035 Diameter of the urethra (mm): 15.7 ± 1.6 vs. 15.7 ± 1.2, p = 0.982 Thickness of compressor urethral (mm): 3.6 ± 0.7 vs. 3.7 ± 1.0, p = 0.928 Length of compressor urethral (mm): 34.5 ± 6.6 vs. 38.2 ± 11.6, p = 0.416 Volume of compressor urethral (mm 3 ): 630.3 ± 301.2 vs. 866.1 ± 514.2, p = 0.247 Length of the anterior part of LAM hiatus (mm): 41.4 ± 3.3 vs. 39.0 ± 5.,p = 0.279 Length of middle part of LAM hiatus (mm): 37.7 ± 5.0 vs. 36.7 ± 4.3, p = 0.641 Length of posterior part of LAM hiatus (mm): 23. ± 6.0 vs. 21.2 ± 4.6, p = 0.451 Volume of LAM (mm 3 ): 27,089.4 ± 5015.0 vs. 27,294.4 ± 4461.4, p = 0.924 Chen et al., 2023 To investigate if urethral calibration with Walther’s urethral sounds may be an effective treatment for OAB syndrome in a prospective placebo-controlled trial Urethral calibration Group (n = 45) vs. control Group (n = 43) at 2 weeks Responsive patients: 14 (31.1%) vs. 4 (9.3%), p < 0.0001 Partially responsive 24 (53.3%) vs. 8 (18.6%), p < 0.0001 Failed 7 (15.6%) vs. 31 (72.1%), p < 0.0001 Urethral calibration Group (n = 45) vs. control Group (n = 43) at 8 weeks Responsive: 14 (31.1%) vs. 4 (9.3%), p < 0.001 Partially responsive 23 (51.1%) vs. 9 (20.9%), p < 0.001 Failed 8 (17.8%) vs. 30 (69.8%), p < 0.001 Tang et al., 2023 46 To compare the efficacy and safety of micro-radiofrequency (RF) therapy through the urethra vs. oral tolterodine tartrate in the treatment of newly diagnosed OAB Pre-treatment parameters between micro-RF group (n = 23) vs. tolterodine group (n = 23) Voiding times/24h: 17 (15, 20) vs. 16 (14, 21) Urgency episodes/24h: 3 (1, 3) vs. 2 (2, 3) UUI episodes/24: 0 (0, 1) vs. 0 (0, 1) Mean volume per micturition: 97 (75,115) vs. 97 (84, 121) OABSS: 10 (9, 12) vs. 11 (9, 11) QoL score: 6 (5, 6) vs. 6 (6, 6) Post-treatment parameters between micro-RF group (n = 23) vs. tolterodine group (n = 23) Voiding times/24h: 10 (9, 11) vs. 13 (11, 15) Urgency episodes/24h: 1 (0, 1) vs. 2 (1, 2) UUI episodes/24: 0 (0, 0) vs. 0 (0, 0) Mean volume per micturition: 160 (145, 182) vs. 130 (110, 150) OABSS: 6 (5, 7) vs. 8 (7, 10) QoL score: 3 (2, 3) vs. 4 (3, 5) Xu et al., 2022 To evaluate the efficacy and safety of low power micro radiofrequency (RF) therapy (µRFthera®) through urethra in the treatment of OAB through a prospective, single-blind, placebo-controlled, multi-center clinical protocol Trial Group (n = 76) vs. control Group (n = 38) FAS 51(67.1%) vs. 10 (26.3%), p = 0.00 PPS 51(76.1%) vs. 10(26.3%), p = 0.00 SA 46(60.5%) vs. 10(26.3%), p = 0.001 Micturition/24h 10.38 ± 4.29 vs. 13.51 ± 6.87, p = 0.0066 Urgency episodes/24h 7.44 ± 4.64 vs. 12.26 ± 7.64, p = 0.004 Quality of life score − 2.11 ± 1.49 vs. -0.60 ± 0.86, p < 0.001 Adverse events 28.9% (22/76) vs. 50.0% (19/38) 3.3. Anatomical changes in urethral complex and correlation with OAB Wang et al. reported that OAB is associated with structural alterations in urethral continence mechanisms. OAB patients showed reduced urethral sphincter thickness (2.2 ± 0.5 mm vs. 2.7 ± 0.3 mm) and volume (2558.6 ± 703.2 mm³ vs. 3267.3 ± 681.9 mm³), lower compressor urethrae volume (630.3 ± 301.2 mm³ vs. 866.1 ± 514.2 mm³), and a more relaxed anterior levator ani muscle hiatus compared to healthy controls. The bladder detrusor was also significantly thicker (3.1 ± 0.7 mm vs. 1.9 ± 0.3 mm) and more voluminous (50,632.0 ± 19,724.7 mm³ vs. 23,386.6 ± 7826.3 mm³), likely reflecting frequent contractions 13 . Complementing these findings, Chen et al. showed that urethral obstruction contributes to OAB symptoms and that restoring urethral patency through calibration improved outcomes: at eight weeks, 31.1% (n = 14) of women in the treatment group were fully responsive versus 9.3% (n = 4) in the placebo group, and at least partial response was observed in 51.1% (n = 23) versus 20.9% (n = 9) 14 . The integration of these findings suggests that while OAB is often associated with specific anatomical weaknesses of the urethral sphincter, de novo OAB following mid-urethral sling surgery represents a distinct clinical entity primarily driven by iatrogenic factors. As demonstrated by Serati et al., the significantly higher PdetQmax values in non-responders (30.6 ± 8.2 vs. 19.9 ± 4.5 cmH 2 O, p = 0.003) confirm that this postoperative urgency is frequently a result of increased outflow resistance and the efficacy of pharmacological therapy is markedly reduced, with a success rate of only 29.3% 15 . 3.4. Correlation between urethrogenic OAB and pelvic floor In an earlier study, Shafik et al. demonstrated the role of pelvic floor muscle (PFM) contractions in patients with OAB, suggesting that their therapeutic effect is mediated through the voluntary urinary inhibition refle 16 . Urgency typically triggers pelvic floor contractions, which contribute to the active component of abdominal pressure transmission (a.p.t.). Urodynamic assessments by Cucchi et al. in women with stress urinary incontinence (SUI, Group 1) and mixed urinary incontinence (MUI, Group 2) showed that MUI patients exhibited both leaks due to abdominal pressure rises and involuntary detrusor contractions preceded by urgency, which could initially be voluntarily inhibited. Pressure transmission ratio (PTR) and maximum urethral pressures during holding (hMUP) differed significantly between the groups ( P < 0.001), highlighting the critical role of the pelvic floor in modulating OAB symptoms 17 . 3.5. Urethral function and urodynamic parameters Recent studies have investigated urethral pressure variations and urodynamic parameters in women with OAB with or without incontinence. Continuous urethral pressure profiling revealed that ‘urethral instability’ —defined as pressure changes > 15 cmH₂O—was highly prevalent, particularly among women with OAB (36.5 cmH₂O) compared with stress urinary incontinence (SUI, 14.9 cmH₂O) and mixed incontinence (19.3 cmH₂O) ( p < 0.05) 18 . Urodynamic studies introduced a novel flow index (FI), calculated as the ratio of average to maximum urine flow, which was significantly lower in pure OAB patients compared with pure SUI patients (0.45 ± 0.08 vs. 0.53 ± 0.09, P < 0.001), and similarly lower in combined OAB groups (pure OAB + MUI-OAB) versus combined SUI groups (0.47 ± 0.11 vs. 0.53 ± 0.09, P 0.5) 19 . Some studies reported that intraurethral pressure falls during or immediately after a squeeze occurred more frequently in women with established incontinence (66%) compared with treatment-naïve incontinent women (35%) and asymptomatic controls (25%, P < 0.001) 20,21 . However, studies examining the temporal relationship between lower urinary tract sensation and detrusor or urethral pressure changes found no consistent pattern, indicating that heightened sensation during detrusor overactivity or incontinence episodes cannot be reliably explained by measurable changes in bladder or urethral pressures 22 , 23 . 3.6. Treatment effects on urethral and bladder physiology Current perception threshold (CPT) testing, which evaluates A-β, A-δ, and C fiber function, has been widely used to assess urethral and bladder sensory abnormalities in women with OAB and UUI 24 – 26 . Kenton et al. compared 13 women with idiopathic UUI to 48 asymptomatic controls and found significantly higher urethral CPTs at 2000, 250, and 5 Hz in the UUI group, whereas bladder CPTs were similar 24 . After adjusting for age and parity, urethral CPT at 5 Hz remained significantly elevated (p = 0.013), reinforcing the impact of urethral sensory dysfunction, particularly C-fibers, in aging-related OAB 24 . Ichiyanagi et al. retrospectively analysed 53 patients with and without DO and observed that median proximal urethral CPT at 3 Hz was significantly higher in neurogenic and idiopathic DO (11.3 and 9.0 mA) compared to normal controls (2.8 mA; P < 0.05), and in patients with UUI versus non-UUI (12.5 vs. 5.4 mA; P < 0.05). CPTs were not associated with bladder capacity, highlighting that hyposensitive C-fibers of the proximal urethra contribute to the development of both urodynamic DO and UUI 25 . Finally, a randomized placebo-controlled study by Vijaya et al. evaluated the effect of tolterodine on urethral and bladder CPT in 20 women with idiopathic DO. After one week of treatment, tolterodine significantly increased urethral and bladder CPTs at 5 Hz and 250 Hz, whereas no changes were observed in the placebo group. Bladder CPT at 5 Hz was significantly higher compared to placebo (P < 0.05), indicating that antimuscarinic therapy can modulate urethral and bladder sensory function, particularly C- and Aδ-fiber-mediated pathways. Collectively, these studies demonstrate a consistent association between elevated urethral CPTs, C-fiber dysfunction, and impaired urethral sensory function in OAB/UUI, and suggest that both aging and pharmacologic modulation can influence urethral afferent signaling. 3.7. Urethrogenic OAB and Sacral neuromodulation (SNM) Across the included studies, sacral neuromodulation (SNM) achieved clinical response rates ranging from 68% to 76.9%, with significant improvements in urinary symptoms, pad use, and quality-of-life measures 27 . Pathological urethral pressure fluctuations during bladder filling were highly prevalent at baseline (> 31 cm H₂O in 84% of patients) and decreased to 29% after six months of SNM 27 . In another cohort, urethral instability (> 15 cm H₂O) was present in 18 of 19 patients at baseline and in 12 of 13 successfully treated patients; after six months, urethral instability resolved in 7 responders, whereas detrusor DO resolved in only one 28 . Short-term assessments before and two weeks after stage 1 SNM implantation showed no significant changes in periurethral sensory thresholds or electromyographic parameters, and baseline urethral sensory function was similar between responders and non-responders; however, responders exhibited trends toward larger, longer, and more complex urethral motor unit action potentials at baseline 28 . In Wenzler et al study, CPT testing one month after SNM showed significant increases in bladder values at 2000 Hz (p = 0.033) and changes at 250 Hz, while urethral CPT values and 5 Hz measurements showed minimal or no change 29 . Overall, the included studies reported frequent baseline urethral abnormalities in OAB and variable modulation of both bladder and urethral function during SNM. 3.8. Micro-radiofrequency (mRT) and urethrogenic OAB Recent clinical trials have shown that micro-radiofrequency (mRF) therapy is a safe and effective treatment for overactive bladder (OAB), with outcomes superior or comparable to standard pharmacotherapy 30 , 31 . The therapy applies low-temperature energy (40–55°C) to urethral and vaginal wall tissues, inducing collagen contraction and remodelling, which enhances urethral support and stability. These anatomical and tissue-level effects likely contribute to modulation of urethral sensory input and reinforcement of the urethra-bladder inhibitory reflex, resulting in improved urethral closure, suppression of detrusor overactivity, and enhanced pelvic floor stability 30 , 31 . Xu et al. reported a 75.4% response rate in the mRF group at 12 weeks, defined as a ≥ 50% reduction in urgency episodes, compared to 20% in the control group (p = 0.001) 30 . Similarly, Tang et al. demonstrated significant reductions in micturition frequency (from 12.33 ± 3.01 to 8.07 ± 1.62) and urgency episodes, outperforming tolterodine (p = 0.012) 31 . 3.9. Bias assessment Fifteen non-randomized studies were assessed using the ROBINS-I tool and were found to have an overall high risk of bias (Fig. 2 A and B ). Eleven studies (73%) were judged at serious risk, while four (27%) were rated as having a critical risk of bias 19 , 20 , 27 , 29 . The main sources of bias were confounding and participant selection, which raised serious or critical concerns in nearly all studies. In contrast, bias due to deviations from intended interventions was generally low. Three randomized controlled trials, evaluated with the RoB 2 tool, showed an overall judgment of “some concerns” 14,26,30 . These trials demonstrated low risk of bias for randomization, intervention adherence, and missing outcome data, but consistently raised concerns regarding outcome measurement and selective reporting (Fig. 3 A and B ). 4. Discussion To our knowledge, this systematic review represents the first structured analysis exploring the functional role of the urethra in the pathophysiology and treatment of OAB. The findings collectively challenge the traditional view of the urethra as a passive conduit for urine and support the concept that it actively participates in bladder regulation through reflex mechanisms, neuromuscular interactions, and structural support 7 , 32 . In this context, the term "urethrogenic OAB" may identify a clinically meaningful phenotype within the broader OAB spectrum, with distinct pathophysiological underpinnings and potentially distinct therapeutic implications 3 , 33 , 34 . Structural evidence from Wang et al. suggested that urethral anatomical changes (reductions in urethral sphincter thickness and volume) are not merely a consequence of OAB but may actively contribute to its onset and perpetuation 13 . These findings are consistent with the concept that a mechanically compromised urethra may fail to adequately modulate afferent signalling from the lower urinary tract, thereby facilitating premature activation of the micturition reflex 7 , 35 . A converging body of evidence from CPT studies highlights the importance of urethral sensory dysfunction in OAB. Kenton et al. demonstrated significantly elevated urethral CPTs at multiple frequencies in women with UUI compared to asymptomatic controls, with the most pronounced differences at 5 Hz, reflecting C-fibre dysfunction, even after adjustment for age and parity 24 . Ichiyanagi et al. similarly reported higher proximal urethral CPTs in patients with detrusor overactivity and UUI, specifically implicating hyposensitive C-fibres as contributors to the development of both urodynamic DO and urge incontinence 25 . In this context, Vijaya et al. demonstrated that antimuscarinic therapy significantly increased CPTs at both urethral and bladder levels indicating that pharmacological modulation of OAB acts through urethral afferent pathways 26 . Urethral pressure variations during bladder filling (Δ ≥ 15 cmH₂O), termed ‘urethral instability’, emerged as a clinically relevant finding in several included studies 4 , 6 , 27 . This condition was significantly more prevalent in women with OAB than in those with SUI or mixed incontinence 36 . For these reasons, urethral pressure profiling, although not yet part of standard urodynamic assessment, may offer additional diagnostic value in selected patients with refractory OAB 34 . The interaction between the urethra and the pelvic floor musculature represents another important dimension of urethrogenic OAB. Cucchi et al. demonstrated that women with MUI exhibit distinct urethral pressure transmission patterns compared to those with pure SUI, with the pelvic floor playing a critical role in modulating urgency through active pressure transmission mechanisms 17 . These findings reinforce the importance of pelvic floor rehabilitation not only in stress incontinence but also in OAB, particularly when a urethrogenic component is suspected 8 , 16 . They also support the rationale for emerging approaches that target urethral and pelvic floor support, such as micro-radiofrequency (mRF) therapy. Micro-radiofrequency therapy offers a mechanistically coherent approach to urethrogenic OAB by targeting collagen remodelling and urethral wall stability. The randomised trial by Xu et al. demonstrated a 75.4% response rate in the mRF group compared to 20% in controls, while Tang et al. reported significant reductions in urgency and micturition frequency, with outcomes superior to tolterodine 30 , 31 . SNM has also shown promising effects on urethral function; however, current data remain inconsistent, limiting definitive pathophysiological interpretations and clinical implications 27 – 29 . An often-overlooked contributor to OAB symptoms is anatomical urethral obstruction. Chen et al. reported that urethral calibration in women with OAB resulted in significantly higher clinical response rates compared with placebo, supporting the concept that increased urethral resistance and altered afferent signalling may contribute to bladder overactivity through a mechanically mediated urethrogenic mechanism 14 . A clinically analogous scenario is represented by de novo OAB following mid-urethral sling insertion, where iatrogenic outlet obstruction, rather than primary DO, appears to drive urgency symptoms, as reflected by the markedly reduced efficacy of antimuscarinic therapy reported by Serati et al. (success rate 29.3%) 15 . Several limitations of the included studies must be acknowledged when interpreting the findings of this review. Firstly, the overall evidence quality was low: most non-randomised studies showed serious or critical risk of bias (ROBINS-I), mainly due to confounding and participant selection, while the three RCTs had ‘some concerns’ (RoB 2), particularly regarding outcome measurement and selective reporting. Marked methodological heterogeneity, across OAB definitions, ‘urethral instability’ thresholds, CPT protocols, and reported outcomes, precluded meta-analysis and limited generalisability. Most studies included exclusively or predominantly women, leaving the urethral role in male OAB largely unexplored. This gap is relevant, as male OAB is often associated with bladder outlet obstruction due to benign prostatic enlargement, where urethral mechanisms may be equally or more important. Future research should prioritise the development of standardised diagnostic criteria for urethrogenic OAB, including validated thresholds for ‘urethral instability’. Well-designed RCTs specifically enrolling patients with a suspected urethrogenic phenotype are needed to evaluate the efficacy of targeted interventions, including mRF therapy, pelvic floor rehabilitation, and SNM. The urethral contribution to male OAB also warrants dedicated investigation. Finally, the integration of urinary biomarkers and microbiome data, as advocated in the ICI-RS 2023 recommendations, with urethral functional parameters may ultimately enable a truly personalised approach to OAB management 33 , 34 . 5. Conclusions This review supports an active role of the urethra in bladder regulation and OAB pathophysiology. Based on current evidence, a clinical framework for suspected urethrogenic OAB may include history of pelvic organ prolapse, stress urinary incontinence, pelvic surgery (especially mid-urethral sling), or oestrogen deficiency; urodynamic evidence of urethral instability or increased outflow resistance; elevated urethral CPTs; and poor response to antimuscarinics or β3-agonists. Although no validated algorithm exists, the coexistence of these features should prompt consideration of a urethral aetiology and tailored management (e.g., hormonal therapy, pelvic floor rehabilitation, SNM or mRF). However, conclusions are limited by heterogeneous designs, small samples, and predominantly female populations. Larger, methodologically standardised studies including more diverse cohorts are needed. Declarations Authors’ contribution: E.R. conceptualization, writing - original draft and writing - review&editing; S. M.: data collection and management, data analysis; L.M.: data collection and management, data analysis; P.V. methodology and data analysis; G. F.: conceptualization and methodology; A.T.: writing - original draft and writing - review&editing; E.F.A.: supervision, writing - review&editing. Conflict of interest: E. Finazzi Agrò is honorarium for speaking from Recordati and Pierre Fabre (Speaker Honorarium). He is consultant and honorarium for speaking from Laborie. Funding or financial disclosure: The authors received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. References Abrams P, Cardozo L, Fall M et al (2003) The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. 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Neurourol Urodyn 23(1):43–47. 10.1002/nau.10172 Ruth KH, Ralf A, Nariman G, Ing G, Adele C, Nadine H (2017) Urethral Pressure Variation: A neglected contributing factor in patients with overactive bladder syndrome? Int Braz J Urol 43(2):272–279. 10.1590/S1677-5538.IBJU.2016.0308 Futyma K, Nowakowski Ł, Bogusiewicz M, Ziętek A, Wieczorek AP, Rechberger T (2017) Use of uroflow parameters in diagnosing an overactive bladder-Back to the drawing board. Neurourol Urodyn 36(1):198–202. 10.1002/nau.22898 Mattiasson A, Teleman P (2006) Abnormal urethral motor function is common in female stress, mixed, and urge incontinence. Neurourol Urodyn 25(7):703–708. 10.1002/nau.20207 Kulseng-Hanssen S, Moe K, Schiøtz HA (2013) How often does detrusor overactivity cause urinary leakage during a stress test in women with mixed urinary incontinence? Int Urogynecol J Pelvic Floor Dysfunct 24(9):1537–1541. 10.1007/s00192-013-2049-3 Rahmanou P, Khullar V (2011) Short-term test-retest reproducibility of urethral pressure profilometry in women with urodynamic stress incontinence with and without detrusor overactivity. Neurourol Urodyn 30(7):1356–1360. 10.1002/nau.21033 Lowenstein L, Pham T, Abbasy S et al (2009) Observations relating to urinary sensation during detrusor overactivity. Neurourol Urodyn 28(6):497–500. 10.1002/nau.20680 Kenton K, Lowenstein L, Simmons J, Brubaker L (2007) Aging and overactive bladder may be associated with loss of urethral sensation in women. Neurourol Urodyn 26(7):981–984. 10.1002/nau.20444 Ichiyanagi O, Nagaoka A, Naito S et al (2019) Possible role of hyposensitivity of C-fiber afferents at the proximal urethra in the development of urge urinary incontinence in patients with detrusor overactivity. Low Urin Tract Symptoms 11(2):O21–O27. 10.1111/luts.12206 Vijaya G, Digesu GA, Derpapas A, Hendricken C, Fernando R, Khullar V (2012) Antimuscarinic effects on current perception threshold: a prospective placebo control study. Neurourol Urodyn 31(1):75–79. 10.1002/nau.21194 Groenendijk PM, Heesakkers JPFA, Lycklama à Nijeholt AAB (2007) Urethral Instability and Sacral Nerve Stimulation-A Better Parameter to Predict Efficacy? J Urol 178(2):568–572. 10.1016/j.juro.2007.03.120 Gleason JL, Kenton K, Greer WJ et al (2013) Sacral neuromodulation effects on periurethral sensation and urethral sphincter activity. Neurourol Urodyn 32(5):476–479. 10.1002/nau.22319 Wenzler DL, Burks FN, Cooney M, Peters KM (2015) Proof of concept trial on changes in current perception threshold after sacral neuromodulation. Neuromodulation 18(3):228–231 discussion 232. 10.1111/ner.12213 Xu ZH, Zhang PF, Wang YF et al (2022) A Multi-Center, Randomized, Blind, Controlled Clinical Trial of the Safety and Efficacy of Micro Radio Frequency Therapy System for the Treatment of Overactive Bladder. Front Med (Lausanne) 9:746064. 10.3389/fmed.2022.746064 Tang M, Liu J, Zhao C et al (2023) Comparison of micro-radiofrequency therapy and tolterodine for the treatment of newly diagnosed overactive bladder: A retrospective cohort study. Front Neurosci 17. 10.3389/fnins.2023.1120843 DeLancey JOL (1994) Structural support of the urethra as it relates to stress urinary incontinence: The hammock hypothesis. Am J Obstet Gynecol 170(6):1713–1723. 10.1016/S0002-9378(94)70346-9 Finazzi Agrò E, Rosato E, Wagg A et al (2024) How do we make progress in phenotyping patients with LUT such as OAB and underactive detrusor, including using urine markers and microbiome data, in order to personalize therapy? ICI-RS 2023: Part 1. Neurourol Urodyn . Published online January 4. 10.1002/nau.25377 Finazzi Agrò E, Rosato E, Wagg A et al (2024) How do we make progress in phenotyping patients with lower urinary tract such as overactive bladder and underactive detrusor, including using urine markers and microbiome data, to personalize therapy? ICI-RS 2023—Part 2. Neurourol Urodyn . Published online January 4. 10.1002/nau.25379 Rosato E, Vacca L, Lombisani A et al (2025) Is There a Role for Urodynamic Investigation in the Management of Pelvic Organ Prolapse? J Clin Med 14(4):1163. 10.3390/jcm14041163 DeLancey JOL, Trowbridge ER, Miller JM et al (2008) Stress Urinary Incontinence: Relative Importance of Urethral Support and Urethral Closure Pressure. J Urol 179(6):2286–2290. 10.1016/j.juro.2008.01.098 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9152026","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625686245,"identity":"728491d4-703b-41cf-9724-e327f56fbd72","order_by":0,"name":"Eleonora 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09:13:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3595480,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9152026/v1/8815bad0-5c21-470a-bba8-d05c94af3f99.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Urethrogenic Overactive Bladder: A Systematic Review of Pathophysiological Mechanisms and Clinical Implications","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOveractive bladder (OAB) was defined by the International Continence Society (ICS) as a storage symptom syndrome characterised by \u0026lsquo;urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia in the absence of urinary tract infections or other pathology\u0026rsquo; \u003csup\u003e1\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn approximately 50% of cases, OAB is associated with detrusor overactivity (DO) observed during invasive urodynamic studies (iUDS) \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. However, DO and OAB should not be considered synonymous and multiple mechanisms\u0026mdash;linked to the urothelium, suburothelium, urethra, and central nervous system (CNS)\u0026mdash;are believed to contribute to the pathogenesis of OAB \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Among these, the urethrogenic hypothesis proposes that urgency originates in the urethra. In the early 20th century, Barrington and other authors described various micturition reflexes in animal models \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. They defined that micturition reflexes could be evoked by running water through the urethra or by the entry of urine into its proximal part. In patients with stress urinary incontinence (SUI), stimulation of urethral afferents may induce or exacerbate DO. In this case, OAB might seem to originate from the bladder neck \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOther potential urethral contributors to OAB include diminished urethral tone\u0026mdash;often related to oestrogen deficiency in females\u0026mdash;and urethral pressure variations during bladder filling (urethral instability) \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. In patients with pelvic organ prolapse (POP), a vagina, incapable of supporting the bladder neck/proximal urethra stretches receptor and activates prematurely the micturition reflex \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe current European Association of Urology (EAU) Guidelines recommend a stepwise approach to OAB treatment, progressing from behavioural therapies to pharmacological interventions and ultimately surgical options \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. However, phenotyping OAB or DO may lead to more individualized and effective management strategies.\u003c/p\u003e \u003cp\u003eRecently, Peyronnet et al proposed many possible OAB phenotypes according to pathophysiological factors or to urodynamic demonstration of DO \u003csup\u003e3\u003c/sup\u003e. Furthermore, at the ICI-RS 2023 meeting, Finazzi Agr\u0026ograve; et al. emphasised the importance of adopting a comprehensive and personalised approach to phenotyping patients with lower urinary tract symptoms (LUTS), including both OAB and underactive bladder \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAccording to the concept of a future tailored approach to the treatment of OAB, this systematic review aims to summarise the current evidence on the pathophysiology, diagnostic considerations, and therapeutic approaches related to urethrogenic OAB.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThe present SR was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Search strategy\u003c/h2\u003e \u003cp\u003e After registering the protocol with PROSPERO (registration number CRD420250548418), we conducted a comprehensive literature search in PubMed, Embase, and Cochrane CENTRAL, including peer-reviewed studies published between January 2003 and December 2025. The search strategy employed both Medical Subject Headings (MeSH) and free-text terms. Full details of the search protocol are provided in \u003cb\u003eSupplementary File 1\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Inclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eTwo authors (SM and LM) independently screened all titles, abstracts, and full-text records against the eligibility criteria by collecting them in an Excel sheet. In case of any disagreement, a third author (ER) solved the divergence. No automation tools were used.\u003c/p\u003e \u003cp\u003e For this systematic review, we included randomized controlled trials, cohort studies, and case-control studies enrolled both sex. We excluded case reports, surveys, expert opinions, editorials, abstracts, guidelines, review articles, and meta-analyses. Studies involving paediatric populations, neurological patients, or animal/cadaveric models were also excluded. Additionally, studies not addressing overactive bladder in relation to urethral physiology or pathophysiology were not considered. Patients affected by pure SUI were excluded while patients with urge urinary incontinence (UUI) or mixed incontinence (MUI) were considered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Data collection process and data items\u003c/h2\u003e \u003cp\u003eWe collected information on the authors, year of publication, and the institution where the study was conducted. The study design (retrospective, prospective, randomized controlled trial [RCT], or non-randomized controlled trial [NRCT]) was also recorded. For each included study, we extracted data on the number of participants, their age (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, range, and median), and sex distribution (male and female). Finally, we reported the study objectives and a summary of the main results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Reporting bias assessment\u003c/h2\u003e \u003cp\u003eThe risk of bias of each included study was assessed by two review authors working independently using the Cochrane Collaboration Risk of Bias Tool for Randomized Controlled Trials (Rob 2) and the Risk of Bias In Non-randomised Studies of Interventions Version 2 (ROBINS-IV 2) scale for randomized and non-randomized observational studies, respectively.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Study inclusion\u003c/h2\u003e \u003cp\u003eA total of 292 publications were initially identified through database searches. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the flow of information through the different phases of this systematic review, in accordance with PRISMA guidelines \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Ultimately, 18 manuscripts met the eligibility criteria and were included in the final analysis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Study Characteristics\u003c/h2\u003e \u003cp\u003eAmong included eighteen studies, 11 (61.1%) were prospective and 7 (38.9%) retrospective in design. The majority (83.3%, n\u0026thinsp;=\u0026thinsp;15) obtained Institutional Review Board (IRB) approval, while 3 studies (16.7%) did not report ethical approval.\u003c/p\u003e \u003cp\u003eThe total population across all studies comprised 1,134 patients, with individual sample sizes ranging from 10 to 230. Female participants represented the vast majority (81.9%, n\u0026thinsp;=\u0026thinsp;16 studies included only women), whereas 2 studies (18.1%) enrolled both sexes. The mean or median age of participants varied between 42 and 69 years.\u003c/p\u003e \u003cp\u003eAll details are reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003e\u0026ndash;\u003c/b\u003e Characteristics of the included studies, providing an overview of study designs, participating institutions, ethical approval status, and patient demographics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInstitution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDesign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eInstitutional Review Board (IRB) Approval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMattiasson et al., 2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLund University Hospital, Lund, Sweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFutyma et al., 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUniversity of Lublin, Lublin, Poland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetrospective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOAB Group 54.6\u0026thinsp;\u0026plusmn;\u0026thinsp;14.57)\u003c/p\u003e \u003cp\u003eMUI Group 58.03\u0026thinsp;\u0026plusmn;\u0026thinsp;11.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRahmanou et al., 2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSt. Mary\u0026rsquo;s Hospital, Imperial College, London, UK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50 (20\u0026ndash;80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCucchi et al., 2004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePoliclinico S. Matteo, Pavia, Italy; Universita' di Trieste, Italy;\u003c/p\u003e \u003cp\u003eIstituto di Medicina Fisica e Riabilitazione, Udine, Italy;\u003c/p\u003e \u003cp\u003eUniversita' di Pavia, Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetrospective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGroup 2 51\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003cp\u003eGroup 2A 49\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003cp\u003eGroup 2B 52\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKulseng-Hanssen et al., 2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u0026aelig;rum Hospital, Rud, Norway\u003c/p\u003e \u003cp\u003eVestfold Hospital, T\u0026oslash;nsberg, Norway\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetrospective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e51.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKirschner-Hermanns et al., 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUniversity Hospital Friederich Wilhelms, University Bonn, Germany;\u003c/p\u003e \u003cp\u003eThe Federal State Institute of Public Health, The Nikiforov Russian Center of Emergency and Radiation Medicine, Saint-Petersburg, Russian Federation;\u003c/p\u003e \u003cp\u003eLaborie, Mississauga, ON, Canada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOAB Group 60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e \u003cp\u003eMUI Group 58.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLowenstein et al., 2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLoyola Medical Center, Chicago, Illinois;St. Luke\u0026rsquo;s Medical Center, Chicago, Illinois; Rambam Medical Center, Faculty of Medicine, Haifa, Israel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetrospective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBoth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60 (36\u0026ndash;82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKenton et al., 2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLoyola University Medical Center, Maywood, Illinois\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e62\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIchiyanagi et al., 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYamagata University; Yonezawa City Hospital,Yonezawa, Japan;\u003c/p\u003e \u003cp\u003eOkitama General Hospital,Kawanishi town, Japan;\u003c/p\u003e \u003cp\u003eIshigooka Clinic, Yamagata, Japan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetrospective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBoth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e69 (49\u0026ndash;84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWenzler et al., 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eINS, Oakland University, CA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e58.9 (31\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVijaya et al., 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSt. Mary\u0026rsquo;s Hospital, Imperial College, London, UK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e46 (36\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerati et al., 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUniversit\u0026agrave; dell\u0026rsquo;Insubria, Varese, Italy;\u003c/p\u003e \u003cp\u003eIRCCS San Raffaele, Milano, Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGroup 1 65 (54\u0026ndash;77)\u003c/p\u003e \u003cp\u003eGroup 2 62 (52\u0026ndash;81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGleason et al., 2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUniversity of Alabama at\u003c/p\u003e \u003cp\u003eBirmingham, Birmingham, AL, USA;\u003c/p\u003e \u003cp\u003eLoyola University Medical Center, Chicago, IL, USA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e61\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroenendijk et al., 2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeiden University, Leiden and Radboud University Nijmegen (JPFAH), Nijmegen, The Netherlands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e45.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 (31\u0026ndash;58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWang et al., 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShanghai Fifth People\u0026rsquo;s Hospital, Fudan University, Shanghai, China\u003c/p\u003e \u003cp\u003eCollege of Biomedical Engineering and Medical Imaging, Army Medical University, Chongqing, China\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e42\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChen et al., 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe Queens Medical Center, Honolulu, HI John A. Burns School of Medicine, University of Hawai\u0026lsquo;i, Honolulu, HI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64.48\u0026thinsp;\u0026plusmn;\u0026thinsp;13.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTang et al., 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe First Aliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China, Nanjing, Jiangsu, China\u003c/p\u003e \u003cp\u003eCenter for Global Health, School of Public Health,Nanjing Medical University, Nanjing, Jiangsu, China\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBoth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e41.11\u0026thinsp;\u0026plusmn;\u0026thinsp;14.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eXu et al., 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZhejiang Provincial People\u0026rsquo;s Hospital, Hangzhou, China,The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China\u003c/p\u003e \u003cp\u003eZhejiang-California International NanoSystems Institute, Hangzhou, China\u003c/p\u003e \u003cp\u003eSir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBoth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e43.37\u0026thinsp;\u0026plusmn;\u0026thinsp;12.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of study objectives and clinical outcomes.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026deg; of patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eObjectives of the study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eResults\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMattiasson et al., 2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo investigate the urethral motor function in incontinent women\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eUDS parameters in MUI (n\u0026thinsp;=\u0026thinsp;46) vs. UUI (n\u0026thinsp;=\u0026thinsp;21) patients\u003c/span\u003e\u003c/p\u003e \u003cp\u003eMUP (cm\u003csub\u003eH2O\u003c/sub\u003e): 58.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.0 vs. 68.4\u0026thinsp;\u0026plusmn;\u0026thinsp;25.3, p\u0026thinsp;=\u0026thinsp;ns\u003c/p\u003e \u003cp\u003eMUCP (cm\u003csub\u003eH2O\u003c/sub\u003e): 45.6\u0026thinsp;\u0026plusmn;\u0026thinsp;18.0 vs. 62.7\u0026thinsp;\u0026plusmn;\u0026thinsp;24.0, p\u0026thinsp;=\u0026thinsp;0.006\u003c/p\u003e \u003cp\u003eFPL (mm): 29.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 vs. 28.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5, p\u0026thinsp;=\u0026thinsp;ns\u003c/p\u003e \u003cp\u003eAll pressure falls provoked by squeeze (%): 62.2 vs. 57.1, p\u0026thinsp;=\u0026thinsp;ns\u003c/p\u003e \u003cp\u003eQmax (ml/sec): 30.1\u0026thinsp;\u0026plusmn;\u0026thinsp;33.8 (range 5-175) vs. 19.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6 (range 2\u0026ndash;40), p\u0026thinsp;=\u0026thinsp;ns\u003c/p\u003e \u003cp\u003ePdetmax (cm\u003csub\u003eH2O\u003c/sub\u003e): 28.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2 vs. 36.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7, p\u0026thinsp;=\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFutyma et al., 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThe study evaluated if uroflowmetry parameters can aid in diagnosing OAB using a new parameter, the flow index (FI, the ratio of average to maximum urine flow rate) proposed as a potential diagnostic marker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eUDS parameters between OAB Group (n\u0026thinsp;=\u0026thinsp;66) vs. MUI Group (n\u0026thinsp;=\u0026thinsp;142)\u003c/span\u003e\u003c/p\u003e \u003cp\u003eFI: 0.45 (0.08) vs. 0.48 (0.11)\u003c/p\u003e \u003cp\u003eDO: 12/66 (18.2%) vs 18/142 (12.3%)\u003c/p\u003e \u003cp\u003eAFL: 9.75 (4.3\u0026ndash;26.5) vs. 10.50 (4.1\u0026ndash;34.8)\u003c/p\u003e \u003cp\u003eMUF: 22.35 (10.3\u0026ndash;63.6) vs. 23.75 (10.7\u0026ndash;64.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRahmanou et al., 2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo determine and compare reproducibility of UPP and MUCP in women with urodynamic USI without DO (Group 1) and USI with DO (Group 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThere were no significant differences between the groups in terms of age, parity, body mass index, or menopausal status.\u003c/p\u003e \u003cp\u003eGroup 2 exhibited greater intra-subject variability in all UPP parameters (MUCP, MUP, FUL) compared with Group 1. However, none of these parameters showed statistically significant differences between the two groups.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCucchi et al., 2004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo ascertain whether abdominal pressure transmission (APT) to the urethra would be affected by urgency in women with SUI (Group 1\u0026thinsp;=\u0026thinsp;40 patients) or MUI (Group 2\u0026thinsp;=\u0026thinsp;40 patients split in Group 2A and Group 2B for the ability to delay an urgent void at CMG for at least 2 minutes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroups 2A vs 2B duration of urge symptoms 9\u0026thinsp;\u0026plusmn;\u0026thinsp;7 vs. 7\u0026thinsp;\u0026plusmn;\u0026thinsp;6 months.\u003c/p\u003e \u003cp\u003eP-values were \u0026lt;\u0026thinsp;0.001for differences in both PTR\u003csub\u003eave\u003c/sub\u003e and hMUP among Groups 1\u0026ndash;2, 1-2A, and 2A-2B. Differences among Groups 1-2B were not statistically significant.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKulseng-Hanssen et al., 2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo examine how often DO causes leakage during a stress test in women with mixed urinary incontinence MUI and if there are differences between patients with or without DO during the stress test (20 jumping jacks and three forceful coughs)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100% patients leaked during the stress test, 5% due to simultaneous stress test and DO, 87% due to the stress test only, and 8% during the stress test as well as due to DO before or after the stress test. Women with DO have a significantly higher Urgency Incontinence Index and 24-h pad-test leakage (p\u0026thinsp;=\u0026thinsp;0.001 and p\u0026thinsp;=\u0026thinsp;0.046).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKirschner-Hermanns et al., 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo study urethral pressure variations during the filling phase of pressure/flow studies in OAB patients compared with SUI and MUI group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCharacteristics of OAB Group (n\u0026thinsp;=\u0026thinsp;29) vs. SUI Group (n\u0026thinsp;=\u0026thinsp;19) vs. MUI Group (n\u0026thinsp;=\u0026thinsp;31)\u003c/span\u003e\u003c/p\u003e \u003cp\u003ePrevalence of urethral instability (%): 79.3% vs. 47.4% vs. 36.6%\u003c/p\u003e \u003cp\u003ePost-menopausal rate (%): 79.3 vs. 84.2 vs.77.4\u003c/p\u003e \u003cp\u003eMean Δ Pressure (cm\u003csub\u003eH2O\u003c/sub\u003e): 36.5 vs. 14.9 vs. 19.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003cp\u003eMaximum urethral closure pressure (cm\u003csub\u003eH2O\u003c/sub\u003e): 202.1 vs. 114.5 vs. 89.0\u003c/p\u003e \u003cp\u003eMinimum urethral closure pressure (cm\u003csub\u003eH2O\u003c/sub\u003e): 1.0 vs.3.0 vs.3.8\u003c/p\u003e \u003cp\u003eFunctional Urethral Length (mm): 38.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9 vs. 33.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 vs. 32.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003cp\u003eAUC Urethral pressure curves: 1195.7\u0026thinsp;\u0026plusmn;\u0026thinsp;985.6 vs. SUI 549.4\u0026thinsp;\u0026plusmn;\u0026thinsp;273.0 vs. 429.3\u0026thinsp;\u0026plusmn;\u0026thinsp;214.5\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOAB Group with DO vs. OAB Group without DO\u003c/span\u003e\u003c/p\u003e \u003cp\u003eMean urethral pressure (cm\u003csub\u003eH2O\u003c/sub\u003e): 85.5\u0026thinsp;\u0026plusmn;\u0026thinsp;37.0 vs. 45.2\u0026thinsp;\u0026plusmn;\u0026thinsp;30.65, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLowenstein et al., 2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo describe the temporal relationship between increases in bladder sensation and changes in detrusor and/or urethral pressures, and to explore quantitative relationships between the changes in detrusor pressures and changes in urgeometer level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDO vs. DOI: no difference in change in sensation level (p\u0026thinsp;\u0026gt;\u0026thinsp;0.5), no dominant temporal pattern (p\u0026thinsp;=\u0026thinsp;0.84), no evidence that the change in sensation level was more likely to occur before, during, or after DO/DOI episodes\u003c/p\u003e \u003cp\u003eUPP characteristic: the most common pattern seen was an increase in sensation level after a fall in urethral pressure, but no dominant pattern was seen.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKenton et al., 2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo compare CPT in the urethra and bladder of women with idiopathic OAB to asymptomatic controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWomen with UUI were significantly older (62\u0026thinsp;\u0026plusmn;\u0026thinsp;14 vs. 44\u0026thinsp;\u0026plusmn;\u0026thinsp;15, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0005) and more likely to be vaginally parous (92 and 51%, p\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e \u003cp\u003eUrethral CPT at 2,000, 250, and 5 Hz were significantly higher in women with UUI than controls, while bladder CPT were not different between groups (2,000 Hz: 1.15 (0.76\u0026ndash;1.53) vs. 2.63 (1.31\u0026ndash;5.39), p\u0026thinsp;=\u0026thinsp;0.005; 250 Hz: 0.45 (0.33\u0026ndash;0.56) vs. 1.39 (0.69\u0026ndash;2.06), p\u0026thinsp;\u0026lt;\u0026thinsp;0.0005; 5 Hz: 0.11 (0.7\u0026ndash;0.24) vs. 1.14 (1.01\u0026ndash;1.86), p\u0026thinsp;\u0026lt;\u0026thinsp;0.0005). No statistically significant bladder findings.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIchiyanagi et al., 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo investigate associations between urethral sensation and UUI in patients with and without DO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eUDS parameters and urethral CPT of the patients with normal CMG (n\u0026thinsp;=\u0026thinsp;11) vs. idiopathic DO (n\u0026thinsp;=\u0026thinsp;12)\u003c/span\u003e\u003c/p\u003e \u003cp\u003eFirst desire to void (mL): 85 (34\u0026ndash;158) vs. 173 (5\u0026ndash;230)\u003c/p\u003e \u003cp\u003eMCC (mL): 403 (197\u0026ndash;625) vs. 324 (28\u0026ndash;511)\u003c/p\u003e \u003cp\u003eBladder compliance (mL/H2O): 104.7 (29.5\u0026ndash;418.5) vs. 25.5 (0.4\u0026ndash;191.4)\u003c/p\u003e \u003cp\u003eUrethral CPT (mA): 2.8 (1.0\u0026ndash;5.2) vs. 9.0 (2.0\u0026ndash;28.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWenzler et al., 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo investigate if SNM affects perception thresholds of afferent sensory nerve pathways on bladder and urethra after 1 month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOAB-q Score\u003c/span\u003e: 78.33 vs. 31.76 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001)\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOAB QoL\u003c/span\u003e: 30.32 vs. 73.39 (p\u0026thinsp;=\u0026thinsp;0.022)\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCPT\u003c/span\u003e at 250 and 2000 Hz in the bladder: 335.75 mA +/- 358.036 (p\u0026thinsp;=\u0026thinsp;0.033)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVijaya et al., 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo evaluate the effect of Tolterodine vs. placebo on urethra and bladder afferent nerves by evaluating the CPT changes (mA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOnly in the tolterodine ER group (n\u0026thinsp;=\u0026thinsp;10) there was a significantly CPT at 5 and 250 Hz for both urethral and bladder stimulation after 1 week of treatment\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eUrethra CPT\u003c/span\u003e\u003c/p\u003e \u003cp\u003e5 Hz from 1.12 (1.05\u0026ndash;1.27) to 1.30 (1.19\u0026ndash;1.30), p-value 0.04\u003c/p\u003e \u003cp\u003e250 Hz from 1.43 (0.95\u0026ndash;1.88) to 1.84 (1.61\u0026ndash;1.99), p-value 0.01\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBladder CPT\u003c/span\u003e\u003c/p\u003e \u003cp\u003e5 Hz from 0.73 (0.29\u0026ndash;1.01) to 2.96 (2.07\u0026ndash;2.78), p-value 0.01\u003c/p\u003e \u003cp\u003e250 Hz from 1.45 (0.91\u0026ndash;1.90) to 1.76 (1.06\u0026ndash;2.33), p-value 0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerati et al., 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo evaluate Solifenacin efficacy in patients with de novo OAB after TOT (Group 1, n\u0026thinsp;=\u0026thinsp;110) vs naive women with OAB (Group 2, n\u0026thinsp;=\u0026thinsp;120)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eGroup 1 vs. Group 2\u003c/span\u003e\u003c/p\u003e \u003cp\u003eMedian voided vol/micturition ml (IQR): 122 (67\u0026ndash;142) vs 143 (123\u0026ndash;187), (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003cp\u003eMedian change urgency episodes/24h :1.1 vs 2.3, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003cp\u003eMedian change UUI episodes/24h: 0.2 vs 1.1, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003cp\u003eMedian micturitions/24 (%): 10 (6\u0026ndash;15) vs 7, (5\u0026ndash;12) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003cp\u003eMedian USS change: 1.5 vs.2.25, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003cp\u003ePGI-I score\u0026thinsp;\u0026le;\u0026thinsp;2 (%): 36 (32.7) vs. 85, (70.8) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003cp\u003eSymptom severity at OAB-q SF: 28.50 vs. 40.25, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003cp\u003eQoL at OAB-q SF:23.25 vs 34.50, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGleason et al., 2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo characterize the effect of SNM on urethral neuromuscular function in women with refractory OAB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20/26 (76.9%) women responded to SNM with a significant improvements in the UDI-6 and UIQ-7 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003ePre-SNM urethral sensation was not significantly different between responders and non-responders.\u003c/p\u003e \u003cp\u003eCPT and CNE parameters did not significantly differ from baseline after 2 weeks.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroenendijk et al., 2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo evaluate the predictive value of urethral instability and other urodynamic parameters on the efficacy of SNM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13/19 (68%) responded to SNM, 6/15 patients with UI were completely dry and 5/15 had more than a 50% decrease in leakage episodes.\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAt 6 months (baseline vs. follow-up)\u003c/span\u003e\u003c/p\u003e \u003cp\u003en. leaks/24h 13\u0026thinsp;\u0026plusmn;\u0026thinsp;10 vs. 6\u0026thinsp;\u0026plusmn;\u0026thinsp;8, p\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003eLeakage severity 2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68 vs. 1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45, p\u0026thinsp;=\u0026thinsp;0.019\u003c/p\u003e \u003cp\u003en. pads/24h 8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0 vs. 4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2, p\u0026thinsp;=\u0026thinsp;0.002\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAt 6 months (SNM device on vs. SMN device off)\u003c/span\u003e\u003c/p\u003e \u003cp\u003eURI\u0026thinsp;+\u0026thinsp;DO: 4 vs. 8\u003c/p\u003e \u003cp\u003eURI, no DO: 5 vs. 7\u003c/p\u003e \u003cp\u003eNo URI, DO: 1 vs. 0\u003c/p\u003e \u003cp\u003eNo URI or DO: 7 vs. 2\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAt 6 months UDS parameters (baseline vs. follow-up)\u003c/span\u003e\u003c/p\u003e \u003cp\u003eFSF bladder vol (ml): 98\u0026thinsp;\u0026plusmn;\u0026thinsp;88 vs. 235\u0026thinsp;\u0026plusmn;\u0026thinsp;159, p\u0026thinsp;=\u0026thinsp;0.002\u003c/p\u003e \u003cp\u003eMCC (ml): 284\u0026thinsp;\u0026plusmn;\u0026thinsp;108 vs. 346\u0026thinsp;\u0026plusmn;\u0026thinsp;166, p\u0026thinsp;=\u0026thinsp;0.061\u003c/p\u003e \u003cp\u003ePeak detrusor pressure (cm\u003csub\u003eH2O\u003c/sub\u003e): 42\u0026thinsp;\u0026plusmn;\u0026thinsp;33 vs. 25\u0026thinsp;\u0026plusmn;\u0026thinsp;14, p\u0026thinsp;=\u0026thinsp;0.028\u003c/p\u003e \u003cp\u003eVolume at peak bladder pressure (ml): 239\u0026thinsp;\u0026plusmn;\u0026thinsp;140 vs. 317\u0026thinsp;\u0026plusmn;\u0026thinsp;153, p\u0026thinsp;=\u0026thinsp;0.041\u003c/p\u003e \u003cp\u003ePeak urethral pressure during cystometry (cm\u003csub\u003eH2O\u003c/sub\u003e): 121\u0026thinsp;\u0026plusmn;\u0026thinsp;42 vs. 113\u0026thinsp;\u0026plusmn;\u0026thinsp;42, p\u0026thinsp;=\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWang et al., 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo examine the 3D morphological changes of the urination and urinary continence anatomical structures in OAB patients (n\u0026thinsp;=\u0026thinsp;11) compared with healthy volounteers (n\u0026thinsp;=\u0026thinsp;9) in MRI scans\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eMRI parameters in patients with (n\u0026thinsp;=\u0026thinsp;11) and without (n\u0026thinsp;=\u0026thinsp;9) OAB\u003c/span\u003e\u003c/p\u003e \u003cp\u003eThickness of bladder detrusor (mm): 3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 vs. 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3, p\u0026thinsp;=\u0026thinsp;0.000\u003c/p\u003e \u003cp\u003eVolume of bladder detrusor (mm\u003csup\u003e3\u003c/sup\u003e): 50,632.0\u0026thinsp;\u0026plusmn;\u0026thinsp;19,724.7 vs. 23,386.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7826.3, p\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003eThickness of main part of urethral sphincter (mm): 2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 vs. 2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3, p\u0026thinsp;=\u0026thinsp;0.018\u003c/p\u003e \u003cp\u003eVolume of main part of urethral sphincter (mm\u003csup\u003e3\u003c/sup\u003e): 2558.6\u0026thinsp;\u0026plusmn;\u0026thinsp;703.2 vs. 3267.3\u0026thinsp;\u0026plusmn;\u0026thinsp;681.9, p\u0026thinsp;=\u0026thinsp;0.035\u003c/p\u003e \u003cp\u003eDiameter of the urethra (mm): 15.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 vs. 15.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2, p\u0026thinsp;=\u0026thinsp;0.982\u003c/p\u003e \u003cp\u003eThickness of compressor urethral (mm): 3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 vs. 3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0, p\u0026thinsp;=\u0026thinsp;0.928\u003c/p\u003e \u003cp\u003eLength of compressor urethral (mm): 34.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6 vs. 38.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6, p\u0026thinsp;=\u0026thinsp;0.416\u003c/p\u003e \u003cp\u003eVolume of compressor urethral (mm\u003csup\u003e3\u003c/sup\u003e): 630.3\u0026thinsp;\u0026plusmn;\u0026thinsp;301.2 vs. 866.1\u0026thinsp;\u0026plusmn;\u0026thinsp;514.2, p\u0026thinsp;=\u0026thinsp;0.247\u003c/p\u003e \u003cp\u003eLength of the anterior part of LAM hiatus (mm): 41.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3 vs. 39.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.,p\u0026thinsp;=\u0026thinsp;0.279\u003c/p\u003e \u003cp\u003eLength of middle part of LAM hiatus (mm): 37.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0 vs. 36.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3, p\u0026thinsp;=\u0026thinsp;0.641\u003c/p\u003e \u003cp\u003eLength of posterior part of LAM hiatus (mm): 23. \u0026plusmn; 6.0 vs. 21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6, p\u0026thinsp;=\u0026thinsp;0.451\u003c/p\u003e \u003cp\u003eVolume of LAM (mm\u003csup\u003e3\u003c/sup\u003e): 27,089.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5015.0 vs. 27,294.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4461.4, p\u0026thinsp;=\u0026thinsp;0.924\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChen et al., 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo investigate if urethral calibration with Walther\u0026rsquo;s urethral sounds may be an effective treatment for OAB syndrome in a prospective placebo-controlled trial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eUrethral calibration Group (n\u0026thinsp;=\u0026thinsp;45) vs. control Group (n\u0026thinsp;=\u0026thinsp;43) at 2 weeks\u003c/span\u003e\u003c/p\u003e \u003cp\u003eResponsive patients: 14 (31.1%) vs. 4 (9.3%), p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003cp\u003ePartially responsive 24 (53.3%) vs. 8 (18.6%), p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003cp\u003eFailed 7 (15.6%) vs. 31 (72.1%), p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eUrethral calibration Group (n\u0026thinsp;=\u0026thinsp;45) vs. control Group (n\u0026thinsp;=\u0026thinsp;43) at 8 weeks\u003c/span\u003e\u003c/p\u003e \u003cp\u003eResponsive: 14 (31.1%) vs. 4 (9.3%), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003ePartially responsive 23 (51.1%) vs. 9 (20.9%), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003eFailed 8 (17.8%) vs. 30 (69.8%), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTang et al., 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo compare the efficacy and safety of\u003c/p\u003e \u003cp\u003emicro-radiofrequency (RF) therapy through the urethra vs. oral tolterodine tartrate in the treatment of newly diagnosed OAB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePre-treatment parameters between micro-RF group (n\u0026thinsp;=\u0026thinsp;23) vs. tolterodine group (n\u0026thinsp;=\u0026thinsp;23)\u003c/span\u003e\u003c/p\u003e \u003cp\u003eVoiding times/24h: 17 (15, 20) vs. 16 (14, 21)\u003c/p\u003e \u003cp\u003eUrgency episodes/24h: 3 (1, 3) vs. 2 (2, 3)\u003c/p\u003e \u003cp\u003eUUI episodes/24: 0 (0, 1) vs. 0 (0, 1)\u003c/p\u003e \u003cp\u003eMean volume per micturition: 97 (75,115) vs. 97 (84, 121)\u003c/p\u003e \u003cp\u003eOABSS: 10 (9, 12) vs. 11 (9, 11)\u003c/p\u003e \u003cp\u003eQoL score: 6 (5, 6) vs. 6 (6, 6)\u003c/p\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePost-treatment parameters between micro-RF group (n\u0026thinsp;=\u0026thinsp;23) vs. tolterodine group (n\u0026thinsp;=\u0026thinsp;23)\u003c/span\u003e\u003c/p\u003e \u003cp\u003eVoiding times/24h: 10 (9, 11) vs. 13 (11, 15)\u003c/p\u003e \u003cp\u003eUrgency episodes/24h: 1 (0, 1) vs. 2 (1, 2)\u003c/p\u003e \u003cp\u003eUUI episodes/24: 0 (0, 0) vs. 0 (0, 0)\u003c/p\u003e \u003cp\u003eMean volume per micturition: 160 (145, 182) vs. 130 (110, 150)\u003c/p\u003e \u003cp\u003eOABSS: 6 (5, 7) vs. 8 (7, 10)\u003c/p\u003e \u003cp\u003eQoL score: 3 (2, 3) vs. 4 (3, 5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eXu et al., 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTo evaluate the efficacy and safety of low power micro radiofrequency (RF) therapy (\u0026micro;RFthera\u0026reg;) through urethra in the treatment of OAB through a prospective, single-blind, placebo-controlled, multi-center clinical protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eTrial Group (n\u0026thinsp;=\u0026thinsp;76) vs. control Group (n\u0026thinsp;=\u0026thinsp;38)\u003c/span\u003e\u003c/p\u003e \u003cp\u003eFAS 51(67.1%) vs. 10 (26.3%), p\u0026thinsp;=\u0026thinsp;0.00\u003c/p\u003e \u003cp\u003ePPS 51(76.1%) vs. 10(26.3%), p\u0026thinsp;=\u0026thinsp;0.00\u003c/p\u003e \u003cp\u003eSA 46(60.5%) vs. 10(26.3%), p\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003eMicturition/24h 10.38\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29 vs. 13.51\u0026thinsp;\u0026plusmn;\u0026thinsp;6.87, p\u0026thinsp;=\u0026thinsp;0.0066\u003c/p\u003e \u003cp\u003eUrgency episodes/24h 7.44\u0026thinsp;\u0026plusmn;\u0026thinsp;4.64 vs. 12.26\u0026thinsp;\u0026plusmn;\u0026thinsp;7.64, p\u0026thinsp;=\u0026thinsp;0.004\u003c/p\u003e \u003cp\u003eQuality of life score\u0026thinsp;\u0026minus;\u0026thinsp;2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.49 vs. -0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003eAdverse events 28.9% (22/76) vs. 50.0% (19/38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Anatomical changes in urethral complex and correlation with OAB\u003c/h2\u003e \u003cp\u003eWang et al. reported that OAB is associated with structural alterations in urethral continence mechanisms. OAB patients showed reduced urethral sphincter thickness (2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 mm vs. 2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 mm) and volume (2558.6\u0026thinsp;\u0026plusmn;\u0026thinsp;703.2 mm\u0026sup3; vs. 3267.3\u0026thinsp;\u0026plusmn;\u0026thinsp;681.9 mm\u0026sup3;), lower compressor urethrae volume (630.3\u0026thinsp;\u0026plusmn;\u0026thinsp;301.2 mm\u0026sup3; vs. 866.1\u0026thinsp;\u0026plusmn;\u0026thinsp;514.2 mm\u0026sup3;), and a more relaxed anterior levator ani muscle hiatus compared to healthy controls. The bladder detrusor was also significantly thicker (3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 mm vs. 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 mm) and more voluminous (50,632.0\u0026thinsp;\u0026plusmn;\u0026thinsp;19,724.7 mm\u0026sup3; vs. 23,386.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7826.3 mm\u0026sup3;), likely reflecting frequent contractions \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eComplementing these findings, Chen et al. showed that urethral obstruction contributes to OAB symptoms and that restoring urethral patency through calibration improved outcomes: at eight weeks, 31.1% (n\u0026thinsp;=\u0026thinsp;14) of women in the treatment group were fully responsive versus 9.3% (n\u0026thinsp;=\u0026thinsp;4) in the placebo group, and at least partial response was observed in 51.1% (n\u0026thinsp;=\u0026thinsp;23) versus 20.9% (n\u0026thinsp;=\u0026thinsp;9)\u003csup\u003e14\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe integration of these findings suggests that while OAB is often associated with specific anatomical weaknesses of the urethral sphincter, de novo OAB following mid-urethral sling surgery represents a distinct clinical entity primarily driven by iatrogenic factors. As demonstrated by Serati et al., the significantly higher PdetQmax values in non-responders (30.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2 vs. 19.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 cmH\u003csub\u003e2\u003c/sub\u003eO, p\u0026thinsp;=\u0026thinsp;0.003) confirm that this postoperative urgency is frequently a result of increased outflow resistance and the efficacy of pharmacological therapy is markedly reduced, with a success rate of only 29.3%\u003csup\u003e15\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Correlation between urethrogenic OAB and pelvic floor\u003c/h2\u003e \u003cp\u003eIn an earlier study, Shafik et al. demonstrated the role of pelvic floor muscle (PFM) contractions in patients with OAB, suggesting that their therapeutic effect is mediated through the voluntary urinary inhibition refle \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Urgency typically triggers pelvic floor contractions, which contribute to the active component of abdominal pressure transmission (a.p.t.). Urodynamic assessments by Cucchi et al. in women with stress urinary incontinence (SUI, Group 1) and mixed urinary incontinence (MUI, Group 2) showed that MUI patients exhibited both leaks due to abdominal pressure rises and involuntary detrusor contractions preceded by urgency, which could initially be voluntarily inhibited. Pressure transmission ratio (PTR) and maximum urethral pressures during holding (hMUP) differed significantly between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), highlighting the critical role of the pelvic floor in modulating OAB symptoms\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Urethral function and urodynamic parameters\u003c/h2\u003e \u003cp\u003eRecent studies have investigated urethral pressure variations and urodynamic parameters in women with OAB with or without incontinence. Continuous urethral pressure profiling revealed that \u0026lsquo;urethral instability\u0026rsquo; \u0026mdash;defined as pressure changes\u0026thinsp;\u0026gt;\u0026thinsp;15 cmH₂O\u0026mdash;was highly prevalent, particularly among women with OAB (36.5 cmH₂O) compared with stress urinary incontinence (SUI, 14.9 cmH₂O) and mixed incontinence (19.3 cmH₂O) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003csup\u003e18\u003c/sup\u003e. Urodynamic studies introduced a novel flow index (FI), calculated as the ratio of average to maximum urine flow, which was significantly lower in pure OAB patients compared with pure SUI patients (0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 vs. 0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and similarly lower in combined OAB groups (pure OAB\u0026thinsp;+\u0026thinsp;MUI-OAB) versus combined SUI groups (0.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 vs. 0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while no significant difference was found between MUI-SUI and pure SUI groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.5)\u003csup\u003e19\u003c/sup\u003e. Some studies reported that intraurethral pressure falls during or immediately after a squeeze occurred more frequently in women with established incontinence (66%) compared with treatment-na\u0026iuml;ve incontinent women (35%) and asymptomatic controls (25%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003csup\u003e20,21\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, studies examining the temporal relationship between lower urinary tract sensation and detrusor or urethral pressure changes found no consistent pattern, indicating that heightened sensation during detrusor overactivity or incontinence episodes cannot be reliably explained by measurable changes in bladder or urethral pressures\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.6. Treatment effects on urethral and bladder physiology\u003c/h2\u003e \u003cp\u003eCurrent perception threshold (CPT) testing, which evaluates A-β, A-δ, and C fiber function, has been widely used to assess urethral and bladder sensory abnormalities in women with OAB and UUI \u003csup\u003e\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eKenton et al. compared 13 women with idiopathic UUI to 48 asymptomatic controls and found significantly higher urethral CPTs at 2000, 250, and 5 Hz in the UUI group, whereas bladder CPTs were similar\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. After adjusting for age and parity, urethral CPT at 5 Hz remained significantly elevated (p\u0026thinsp;=\u0026thinsp;0.013), reinforcing the impact of urethral sensory dysfunction, particularly C-fibers, in aging-related OAB\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIchiyanagi et al. retrospectively analysed 53 patients with and without DO and observed that median proximal urethral CPT at 3 Hz was significantly higher in neurogenic and idiopathic DO (11.3 and 9.0 mA) compared to normal controls (2.8 mA; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and in patients with UUI versus non-UUI (12.5 vs. 5.4 mA; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). CPTs were not associated with bladder capacity, highlighting that hyposensitive C-fibers of the proximal urethra contribute to the development of both urodynamic DO and UUI\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Finally, a randomized placebo-controlled study by Vijaya et al. evaluated the effect of tolterodine on urethral and bladder CPT in 20 women with idiopathic DO. After one week of treatment, tolterodine significantly increased urethral and bladder CPTs at 5 Hz and 250 Hz, whereas no changes were observed in the placebo group. Bladder CPT at 5 Hz was significantly higher compared to placebo (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), indicating that antimuscarinic therapy can modulate urethral and bladder sensory function, particularly C- and Aδ-fiber-mediated pathways. Collectively, these studies demonstrate a consistent association between elevated urethral CPTs, C-fiber dysfunction, and impaired urethral sensory function in OAB/UUI, and suggest that both aging and pharmacologic modulation can influence urethral afferent signaling.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.7. Urethrogenic OAB and Sacral neuromodulation (SNM)\u003c/h2\u003e \u003cp\u003eAcross the included studies, sacral neuromodulation (SNM) achieved clinical response rates ranging from 68% to 76.9%, with significant improvements in urinary symptoms, pad use, and quality-of-life measures\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Pathological urethral pressure fluctuations during bladder filling were highly prevalent at baseline (\u0026gt;\u0026thinsp;31 cm H₂O in 84% of patients) and decreased to 29% after six months of SNM\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. In another cohort, urethral instability (\u0026gt;\u0026thinsp;15 cm H₂O) was present in 18 of 19 patients at baseline and in 12 of 13 successfully treated patients; after six months, urethral instability resolved in 7 responders, whereas detrusor DO resolved in only one\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Short-term assessments before and two weeks after stage 1 SNM implantation showed no significant changes in periurethral sensory thresholds or electromyographic parameters, and baseline urethral sensory function was similar between responders and non-responders; however, responders exhibited trends toward larger, longer, and more complex urethral motor unit action potentials at baseline\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. In Wenzler et al study, CPT testing one month after SNM showed significant increases in bladder values at 2000 Hz (p\u0026thinsp;=\u0026thinsp;0.033) and changes at 250 Hz, while urethral CPT values and 5 Hz measurements showed minimal or no change\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Overall, the included studies reported frequent baseline urethral abnormalities in OAB and variable modulation of both bladder and urethral function during SNM.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.8. Micro-radiofrequency (mRT) and urethrogenic OAB\u003c/h2\u003e \u003cp\u003eRecent clinical trials have shown that micro-radiofrequency (mRF) therapy is a safe and effective treatment for overactive bladder (OAB), with outcomes superior or comparable to standard pharmacotherapy\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. The therapy applies low-temperature energy (40\u0026ndash;55\u0026deg;C) to urethral and vaginal wall tissues, inducing collagen contraction and remodelling, which enhances urethral support and stability. These anatomical and tissue-level effects likely contribute to modulation of urethral sensory input and reinforcement of the urethra-bladder inhibitory reflex, resulting in improved urethral closure, suppression of detrusor overactivity, and enhanced pelvic floor stability\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eXu et al. reported a 75.4% response rate in the mRF group at 12 weeks, defined as a\u0026thinsp;\u0026ge;\u0026thinsp;50% reduction in urgency episodes, compared to 20% in the control group (p\u0026thinsp;=\u0026thinsp;0.001)\u003csup\u003e30\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSimilarly, Tang et al. demonstrated significant reductions in micturition frequency (from 12.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.01 to 8.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62) and urgency episodes, outperforming tolterodine (p\u0026thinsp;=\u0026thinsp;0.012)\u003csup\u003e31\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.9. Bias assessment\u003c/h2\u003e \u003cp\u003eFifteen non-randomized studies were assessed using the ROBINS-I tool and were found to have an overall high risk of bias (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA \u003cb\u003eand B\u003c/b\u003e). Eleven studies (73%) were judged at serious risk, while four (27%) were rated as having a critical risk of bias\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. The main sources of bias were confounding and participant selection, which raised serious or critical concerns in nearly all studies. In contrast, bias due to deviations from intended interventions was generally low.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThree randomized controlled trials, evaluated with the RoB 2 tool, showed an overall judgment of \u0026ldquo;some concerns\u0026rdquo;\u003csup\u003e14,26,30\u003c/sup\u003e. These trials demonstrated low risk of bias for randomization, intervention adherence, and missing outcome data, but consistently raised concerns regarding outcome measurement and selective reporting (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA \u003cb\u003eand B\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eTo our knowledge, this systematic review represents the first structured analysis exploring the functional role of the urethra in the pathophysiology and treatment of OAB. The findings collectively challenge the traditional view of the urethra as a passive conduit for urine and support the concept that it actively participates in bladder regulation through reflex mechanisms, neuromuscular interactions, and structural support\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. In this context, the term \"urethrogenic OAB\" may identify a clinically meaningful phenotype within the broader OAB spectrum, with distinct pathophysiological underpinnings and potentially distinct therapeutic implications\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eStructural evidence from Wang et al. suggested that urethral anatomical changes (reductions in urethral sphincter thickness and volume) are not merely a consequence of OAB but may actively contribute to its onset and perpetuation\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. These findings are consistent with the concept that a mechanically compromised urethra may fail to adequately modulate afferent signalling from the lower urinary tract, thereby facilitating premature activation of the micturition reflex\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA converging body of evidence from CPT studies highlights the importance of urethral sensory dysfunction in OAB. Kenton et al. demonstrated significantly elevated urethral CPTs at multiple frequencies in women with UUI compared to asymptomatic controls, with the most pronounced differences at 5 Hz, reflecting C-fibre dysfunction, even after adjustment for age and parity\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Ichiyanagi et al. similarly reported higher proximal urethral CPTs in patients with detrusor overactivity and UUI, specifically implicating hyposensitive C-fibres as contributors to the development of both urodynamic DO and urge incontinence\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. In this context, Vijaya et al. demonstrated that antimuscarinic therapy significantly increased CPTs at both urethral and bladder levels indicating that pharmacological modulation of OAB acts through urethral afferent pathways\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eUrethral pressure variations during bladder filling (Δ\u0026thinsp;\u0026ge;\u0026thinsp;15 cmH₂O), termed \u0026lsquo;urethral instability\u0026rsquo;, emerged as a clinically relevant finding in several included studies\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. This condition was significantly more prevalent in women with OAB than in those with SUI or mixed incontinence\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. For these reasons, urethral pressure profiling, although not yet part of standard urodynamic assessment, may offer additional diagnostic value in selected patients with refractory OAB\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe interaction between the urethra and the pelvic floor musculature represents another important dimension of urethrogenic OAB. Cucchi et al. demonstrated that women with MUI exhibit distinct urethral pressure transmission patterns compared to those with pure SUI, with the pelvic floor playing a critical role in modulating urgency through active pressure transmission mechanisms\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. These findings reinforce the importance of pelvic floor rehabilitation not only in stress incontinence but also in OAB, particularly when a urethrogenic component is suspected\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. They also support the rationale for emerging approaches that target urethral and pelvic floor support, such as micro-radiofrequency (mRF) therapy. Micro-radiofrequency therapy offers a mechanistically coherent approach to urethrogenic OAB by targeting collagen remodelling and urethral wall stability. The randomised trial by Xu et al. demonstrated a 75.4% response rate in the mRF group compared to 20% in controls, while Tang et al. reported significant reductions in urgency and micturition frequency, with outcomes superior to tolterodine\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. SNM has also shown promising effects on urethral function; however, current data remain inconsistent, limiting definitive pathophysiological interpretations and clinical implications\u003csup\u003e\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAn often-overlooked contributor to OAB symptoms is anatomical urethral obstruction. Chen et al. reported that urethral calibration in women with OAB resulted in significantly higher clinical response rates compared with placebo, supporting the concept that increased urethral resistance and altered afferent signalling may contribute to bladder overactivity through a mechanically mediated urethrogenic mechanism\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. A clinically analogous scenario is represented by de novo OAB following mid-urethral sling insertion, where iatrogenic outlet obstruction, rather than primary DO, appears to drive urgency symptoms, as reflected by the markedly reduced efficacy of antimuscarinic therapy reported by Serati et al. (success rate 29.3%) \u003csup\u003e15\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSeveral limitations of the included studies must be acknowledged when interpreting the findings of this review. Firstly, the overall evidence quality was low: most non-randomised studies showed serious or critical risk of bias (ROBINS-I), mainly due to confounding and participant selection, while the three RCTs had \u0026lsquo;some concerns\u0026rsquo; (RoB 2), particularly regarding outcome measurement and selective reporting. Marked methodological heterogeneity, across OAB definitions, \u0026lsquo;urethral instability\u0026rsquo; thresholds, CPT protocols, and reported outcomes, precluded meta-analysis and limited generalisability. Most studies included exclusively or predominantly women, leaving the urethral role in male OAB largely unexplored. This gap is relevant, as male OAB is often associated with bladder outlet obstruction due to benign prostatic enlargement, where urethral mechanisms may be equally or more important.\u003c/p\u003e \u003cp\u003eFuture research should prioritise the development of standardised diagnostic criteria for urethrogenic OAB, including validated thresholds for \u0026lsquo;urethral instability\u0026rsquo;. Well-designed RCTs specifically enrolling patients with a suspected urethrogenic phenotype are needed to evaluate the efficacy of targeted interventions, including mRF therapy, pelvic floor rehabilitation, and SNM. The urethral contribution to male OAB also warrants dedicated investigation. Finally, the integration of urinary biomarkers and microbiome data, as advocated in the ICI-RS 2023 recommendations, with urethral functional parameters may ultimately enable a truly personalised approach to OAB management\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis review supports an active role of the urethra in bladder regulation and OAB pathophysiology. Based on current evidence, a clinical framework for suspected urethrogenic OAB may include history of pelvic organ prolapse, stress urinary incontinence, pelvic surgery (especially mid-urethral sling), or oestrogen deficiency; urodynamic evidence of urethral instability or increased outflow resistance; elevated urethral CPTs; and poor response to antimuscarinics or β3-agonists. Although no validated algorithm exists, the coexistence of these features should prompt consideration of a urethral aetiology and tailored management (e.g., hormonal therapy, pelvic floor rehabilitation, SNM or mRF). However, conclusions are limited by heterogeneous designs, small samples, and predominantly female populations. Larger, methodologically standardised studies including more diverse cohorts are needed.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contribution:\u0026nbsp;\u003c/strong\u003eE.R. conceptualization, writing - original draft and writing - review\u0026amp;editing; S. M.: data collection and management, data analysis; L.M.: data collection and management, data analysis; P.V. methodology and data analysis; G. F.: conceptualization and methodology; A.T.: writing - original draft and writing - review\u0026amp;editing; E.F.A.: supervision, writing - review\u0026amp;editing.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConflict of interest:\u003c/strong\u003e E. Finazzi Agr\u0026ograve; is honorarium for speaking from Recordati and Pierre Fabre (Speaker Honorarium). He is consultant and honorarium for speaking from Laborie.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding or financial disclosure:\u0026nbsp;\u003c/strong\u003eThe authors received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAbrams P, Cardozo L, Fall M et al (2003) The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. 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Published online January 4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/nau.25377\u003c/span\u003e\u003cspan address=\"10.1002/nau.25377\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFinazzi Agr\u0026ograve; E, Rosato E, Wagg A et al (2024) How do we make progress in phenotyping patients with lower urinary tract such as overactive bladder and underactive detrusor, including using urine markers and microbiome data, to personalize therapy? ICI-RS 2023\u0026mdash;Part 2. \u003cem\u003eNeurourol Urodyn\u003c/em\u003e. Published online January 4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/nau.25379\u003c/span\u003e\u003cspan address=\"10.1002/nau.25379\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosato E, Vacca L, Lombisani A et al (2025) Is There a Role for Urodynamic Investigation in the Management of Pelvic Organ Prolapse? J Clin Med 14(4):1163. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm14041163\u003c/span\u003e\u003cspan address=\"10.3390/jcm14041163\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeLancey JOL, Trowbridge ER, Miller JM et al (2008) Stress Urinary Incontinence: Relative Importance of Urethral Support and Urethral Closure Pressure. J Urol 179(6):2286\u0026ndash;2290. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.juro.2008.01.098\u003c/span\u003e\u003cspan address=\"10.1016/j.juro.2008.01.098\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjur","sideBox":"Learn more about [World Journal of Urology](https://link.springer.com/journal/345)","snPcode":"345","submissionUrl":"https://submission.nature.com/new-submission/345/3","title":"World Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"overactive bladder, urethra, urethrogenic overactive bladder, detrusor overactivity, urinary incontinence, urgency","lastPublishedDoi":"10.21203/rs.3.rs-9152026/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9152026/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eWhile Overactive Bladder (OAB) is traditionally viewed as a detrusor-centric dysfunction, emerging evidence suggests the urethra plays a critical role in its pathogenesis. This review aims to evaluate the contribution of urethral mechanisms\u0026mdash;including pressure variations, sensory thresholds, and morphological changes\u0026mdash;to OAB symptoms and to explore the efficacy of urethra-targeted interventions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA comprehensive review of clinical studies was conducted, analysing urodynamic data, Current Perception Thresholds (CPT), and magnetic resonance imaging (MRI) findings across cohorts of patients with OAB, mixed urinary incontinence (MUI), and asymptomatic controls. Therapeutic outcomes from sacral neuromodulation (SNM), urethral calibration, and micro-radiofrequency (RF) therapy were also synthesized.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePatients with OAB and MUI frequently exhibit significant \u0026lsquo;urethral instability\u0026rsquo; and pressure fluctuations compared to those with pure SUI. Sensory testing demonstrated that OAB is associated with altered urethral perception thresholds, suggesting a state of hypersensitivity or neural dysfunction in the lower urinary tract. Furthermore, imaging data identified distinct structural and morphological differences in the urethral sphincter and surrounding musculature of symptomatic patients. Finally, clinical outcomes indicate that interventions specifically targeting the urethra\u0026mdash;ranging from mechanical calibration to neuromodulation and thermal therapies\u0026mdash;result in a meaningful reduction of urgency episodes and an overall improvement in quality of life.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe urethra acts as a dynamic modulator of the micturition reflex rather than a passive conduit. Urethral sensory and mechanical dysfunctions are key components of OAB, and therapies targeting these urethral pathways offer promising alternatives for patients who do not respond to traditional detrusor-focused treatments.\u003c/p\u003e","manuscriptTitle":"Urethrogenic Overactive Bladder: A Systematic Review of Pathophysiological Mechanisms and Clinical Implications","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-21 15:16:02","doi":"10.21203/rs.3.rs-9152026/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-02T12:15:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-24T07:50:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"227639764447393740119672332717795856003","date":"2026-04-19T11:07:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-16T09:50:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"16681203176382601511286146988868103469","date":"2026-04-16T09:05:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"296934758051833219990374916154657023749","date":"2026-04-16T07:37:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"235219092047899545577550606998654018315","date":"2026-04-16T06:30:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-14T08:59:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-18T17:30:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-18T17:03:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Urology","date":"2026-03-17T19:07:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjur","sideBox":"Learn more about [World Journal of Urology](https://link.springer.com/journal/345)","snPcode":"345","submissionUrl":"https://submission.nature.com/new-submission/345/3","title":"World Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ea291313-f530-47f9-973e-0e1b7aa3ad2b","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-02T12:15:10+00:00","index":40,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-21T15:16:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 15:16:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9152026","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9152026","identity":"rs-9152026","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}