Current literature suggests that several pathophysiological factors and mechanisms might be responsible for the nonspecific symptom complex of overactive bladder (OAB).To provide a comprehensive analysis of the potential pathophysiology underlying detrusor overactivity (DO) and OAB.A PubMed-based literature search was conducted in April 2018, to identify randomised controlled trials, prospective and retrospective series, animal model studies, and reviews.OAB is a nonspecific storage symptom complex with poorly defined pathophysiology. OAB was historically thought to be caused by DO, which was either "myogenic" (urgency initiated from autonomous contraction of the detrusor muscle) or "neurogenic" (urgency signalled from the central nervous system, which initiates a detrusor contraction). Patients with OAB are often found to not have objective evidence of DO on urodynamic studies; therefore, alternative mechanisms for the development of OAB have been postulated. Increasing evidence on the role of urothelium/suburothelium and bladder afferent signalling arose in the early 2000s, emphasising an afferent "urotheliogenic" hypothesis, namely, that urgency is initiated from the urothelium/suburothelium. The urethra has also recently been regarded as a possible afferent origin of OAB-the "urethrogenic" hypothesis. Several other pathophysiological factors have been implicated, including metabolic syndrome, affective disorders, sex hormone deficiency, urinary microbiota, gastrointestinal functional disorders, and subclinical autonomic nervous system dysfunctions. These various possible mechanisms should be considered as contributing to diagnostic and treatment algorithms.There is a temptation to label OAB as "idiopathic" without obvious causation, given the poorly understood nature of its pathophysiology. OAB should be seen as a complex, multifactorial symptom syndrome, resulting from multiple potential pathophysiological mechanisms. Identification of the underlying causes on an individual basis may lead to the definition of OAB phenotypes, paving the way for personalised medical care.Overactive bladder (OAB) is a storage symptom syndrome with multiple possible causes. Identification of the mechanisms causing a patient to experience OAB symptoms may help tailor treatment to individual patients and improve outcomes.Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

In 45 years, the definitions and practice of the urodynamically based overactive bladder (OAB)/detrusor overactivity (DO) system have failed to adequately address pathogenesis and cure of urinary urge incontinence, frequency and nocturia.We analysed the OAB syndrome with reference to the Integral Theory paradigm's (ITS) binary feedback system, where OAB in the female is viewed as a prematurely activated, but otherwise normal micturition caused mainly, but not entirely, by ligament damage/laxity. The ITS Clinical Assessment Pathway which details the relationships between structural damage (prolapse), ligaments and dysfunction (symptoms) is introduced.The ITS was able to "better explain" OAB pathophysiology in anatomical terms with reference to the binary model. The phasic patterns diagnostic of "detrusor overactivity" are explained as a struggle for control by the closure and micturition reflexes. The exponentially determined relationship between urethral diameter and flow explains why obstructive patterns occur, why they do not and why urine may leak with no recorded pressure. Mechanically supporting ligaments ("simulated operations") during urodynamic testing can improve low urethral pressure, negative pressure during coughing with SUI and diminish urge sensation or even DO patterns, transforming urodynamics from non-predictive test to accurate predictor of continence surgery results. High cure rates for OAB by daycare repair of damaged ligaments is a definitive test of the binary system's validity.Conceptual progression of OAB to the Integral Theory paradigms's prematurely activated micturition validates OAB component symptoms as a syndrome, explains pathogenesis, and unlocks a new way of understanding, diagnosing, treating and researching OAB.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

We determined the effect of caffeine restriction and fluid manipulation in the treatment of patients with urodynamic stress incontinence and detrusor overactivity.This was a 4-week randomized, prospective, observational crossover study in 110 women with urodynamic stress incontinence (USI) or idiopathic detrusor overactivity (IDO) to determine the effect of caffeine restriction, and of increasing and decreasing fluid intake on urinary symptoms. Data were recorded in a urinary diary for the entire study period on urgency episodes, frequency, pad weight increase, wetting episodes and quality of life.A total of 69 women with a mean age of 54.8 years completed the study, including 39 with USI and 30 with IDO. In the IDO group decreasing fluid intake significantly decreased voiding frequency, urgency and wetting episodes with improved quality of life. In the USI group there was a significant decrease in wetting episodes when fluid intake was decreased. Changing from caffeine containing to decaffeinated drinks produced no improvement in symptoms.Conservative and life-style interventions are first line treatments in the management of incontinence and storage lower urinary tract symptoms. This study shows that a decrease in fluid intake improves some of these symptoms in patients with USI and IDO and, therefore, it should be considered when treating such patients.

To investigate whether vaginal estrogen cream combined with tolterodine is more effective than tolterodine alone in the treatment of postmenopausal women with overactive bladder (OAB).

The aim of this study was to compare the efficacy of the ultralow-dose estradiol vaginal ring with that of oral oxybutynin in the treatment of overactive bladder in postmenopausal women.Postmenopausal women with an overactive bladder were recruited from the general gynecology clinic. Participants were randomized to receive either the ultralow-dose estradiol vaginal ring or oral oxybutynin for 12 weeks. The primary outcome was a decrease in the number of voids in 24 hours. The secondary outcomes were quality-of-life questionnaires, vaginal pH levels, and vaginal maturation index.Fifty-nine women were enrolled. Thirty-one were randomized to receive oxybutynin, whereas 28 received the estradiol vaginal ring. Women who received oxybutynin had a mean decrease of 3.0 voids per day, and women who received the vaginal ring had a mean decrease of 4.5 voids per day, with no significant difference between the groups. There was a significant improvement in Urogenital Distress Inventory and Incontinence Impact Questionnaire scores in both groups, with no significant difference in improvement between the two groups.Ultralow-dose estradiol-releasing vaginal ring and oral oxybutynin seem to be similarly effective in decreasing the number of daily voids in postmenopausal women with overactive bladder.

The aim of the study was to compare the effectiveness and safety of solifenacin succinate tablets alone or combined with local estrogen for overactive bladder treatment in postmenopausal women.This multicenter, randomized, open, parallel-controlled clinical trial enrolled 104 women between January 2012 and August 2013. Participants meeting the inclusion criteria were randomized 1:1 to 12 weeks of treatment with group A (solifenacin 5 mg qd + promestriene vaginal capsules intravaginally) or group B (solifenacin 5 mg qd). Before and after 12 weeks of treatment, symptoms (urinary urgency, frequency, and urge incontinence) were analyzed. Our primary outcome was the change from baseline to the end of treatment in the mean number of voids in 24 hours. Quality of life (QoL) was assessed using International Prostate Symptom Score and Overactive Bladder Symptom Score questionnaires and safety according to the incidence of adverse events. The t test or the Mann-Whitney U test was used to compare continuous variables, and the χ(2) test or Fisher's exact test was used to compare categorical variables.The median decreases in the mean number of voids in 24 hours in groups A and B were 5.2. and 4.3, respectively, which were not significantly different. The median decreases in urgency episodes in groups A and B were 2.0 and 2.5, respectively. In addition, the QoL scores significantly changed in both groups (both P < 0.05). The most common adverse event was dry mouth (19.2% in both groups).Solifenacin with or without local estrogen was effective and safe for overactive bladder treatment in postmenopausal women. The addition of local estrogen improved subjective feelings and QoL.

To check evidence that symptoms identical with those constituting "underactive bladder" (UAB) and "overactive bladder" (OAB) are caused by apical prolapse and cured by repair thereof.After repair of apical prolapse by mesh tape reinforcement of lax uterosacral ligaments (USL) data form 1,671 women were retrospectively examined to determine the presence of OAB and UAB symptoms and to check, how many were cured surgically. Thereby 3 different techniques were performed: elevate (n = 277), "Posterior IVS" (n = 1,049), and TFS cardinal (CL)/USL (n = 345).Symptoms identical with those comprising UAB and OAB were cured in up to 80% of cases following surgical repair of the CL/USL complex.These symptoms may be consistent with symptoms of the posterior fornix syndrome, which comprises 4 main symptoms: micturition difficulties, urge/frequency, nocturia, chronic pelvic pain, all consequent on USL laxity. Surgical cure of OAB and UAB is inconsistent with existing definitions, which imply pathogenesis of the detrusor muscle itself. A reconsideration and reformulation of existing definitions may be required. Altering UAB definition to "bladder emptying difficulties" and return to former definitions for OAB such as "detrusor" or "bladder instability" may help to restore compatibility with surgical cure of these conditions.© 2019 S. Karger AG, Basel.

Simulated operations (SOs) are a direct application of the Integral Theory (IT) mantras, "structure and function are related" and "restore the structure and you will improve the function". SOs performed in a clinic setting, are the most effective way possible to test the validity of the IT predictions: stress urinary incontinence (SUI) and urge are mainly caused by laxity in the vagina or its supporting ligaments. The SUI prediction of the IT is validated if a hemostat applied vaginally in the position of the midurethra to mechanically support the pubourethral ligament (PUL) immediately stops urine loss on coughing. The urge and chronic pelvic pain (CPP) predictions of the IT are similarly validated if a patient states her urge and pain symptoms are relieved by insertion of the bottom blade of a bivalve speculum which supports the uterosacral ligaments (USLs). An important use of SOs is to preoperatively assess (by the hemostat test) whether sling surgery for SUI is likely to cure the patient. Similarly, the speculum is very useful for diagnosing whether severe urge or pain symptoms in a woman with minimal prolapse are originating from weak USLs. If digital support of a cystocele relieves urge symptoms, the patient can reasonably be informed that a cystocele repair should improve the urge as well her cystocele prolapse. Used intraoperatively under spinal anesthesia, SOs can determine whether a sling is sufficiently tight to reverse the loose PUL which is causing the SUI. Approximating both cardinal ligaments (CLs) intraoperatively can result in a remarkable disappearance of a transverese defect cystocele; approximating USLs intraoperatively can give an indication of how effective a USL plication would be surgically.2024 Annals of Translational Medicine. All rights reserved.

The key messages from the Shkarupa native cardinal/uterosacral ligament (CL/USL) study, was that, in premenopausal women, ligament repair alone is sufficient for cure of pelvic organ prolapse (POP) and urgency, achieving cure rates of 85.7% for POP and 81.6% for urgency at 12 months. However, in postmenopausal women, the cure rates were 20.5% for POP and 33.3% for urge at 12 months. The Prospect Trial recorded 21% for native vaginal repair at 12 months. The poor POP cure rate in the Prospect Trial, and the rapid deterioration in the post-menopausal CL/USL repair group, can be explained by known biomechanics. The vagina has little structural strength. Ligaments, with a much higher breaking strain, are the main structural support of pelvic organs. Yet, even native ligament repair reported very low cure rates at 12 months. The poor results in postmenopausal women with native ligament repair can be explained by collagen breakdown after the menopause, as collagen is the key structural component of ligaments. An important question posed in the ligament repair study was, "What happens to women cured by ligament repair after the menopause when the collagen leaches out of the ligaments?". One recommendation was that collagen creating tapes be routinely applied in prolapse surgery and OAB, at least in postmenopausal women. The recommendation for routine collagen-creating ligament repair methods, especially in older women, are supported by high 5-year surgical cure rates in 70-year-old Japanese women, 91.2% for POP, at 12 months, falling to 79.0 at 60 months, using collagen creating Tissue Fixation System (TFS) minislings.2024 Annals of Translational Medicine. All rights reserved.