Central Control Circuit for Context-Dependent Micturition.

Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here, we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) is electrophysiologically distinct from their Crh-negative neighbors and sends glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with and is sufficient to drive bladder contraction, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and whose activity modulates hierarchy-dependent micturition. Taken together, our results indicate that PMC Crh-expressing neurons are likely the integration center for context-dependent micturition behavior.

Comparative analysis of real-world adherence and persistence patterns with vibegron, mirabegron, and anticholinergics in patients with overactive bladder: A retrospective claims study.

INTRODUCTION: Vibegron is a selective ß3-adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics. MATERIALS AND METHODS: This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up. RESULTS: The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001). CONCLUSION: In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics.

Social isolation uncovers a circuit underlying context-dependent territory-covering micturition.

The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploited a behavioral paradigm in which mice, depending on strain, social experience, and sensory context, either vigorously cover an arena with small urine spots or deposit urine in a few isolated large spots. We refer to these micturition modes as, respectively, high and low territory-covering micturition (TCM) and find that the presence of a urine stimulus robustly induces high TCM in socially isolated mice. Comparison of the brain networks activated by social isolation and by urine stimuli to those upstream of the PMC identified the lateral hypothalamic area as a potential modulator of micturition modes. Indeed, chemogenetic manipulations of the lateral hypothalamus can switch micturition behavior between high and low TCM, overriding the influence of social experience and sensory context. Our results suggest that both inhibitory and excitatory signals arising from a network upstream of the PMC are integrated to determine context- and social-experience-dependent micturition patterns.

Periaqueductal gray subregions connectivity and its association with micturition desire-awakening function.

Existing literature strongly supports the idea that children with primary nocturnal enuresis (PNE) have brainstem abnormalities. However, the connection between pre-micturition arousal responses and brain functional connectivities is still not clearly defined. Our study investigated the correlation between the gradations of micturition desire-awakening (MDA) functionality and the functional connectivity of the midbrain periaqueductal gray (PAG), a pivotal brainstem hub implicated in the neural regulation of micturition in humans. Neuroimaging and behavioral data from 133 patients with PNE and 40 healthy children were acquired from functional magnetic resonance imaging (fMRI) and precise clinical observations, respectively. The whole-brain correlation analyses were undertaken to elucidate the complex connectivity patterns between the subregions of PAG and the cerebral cortex, with a focus on their correlation to the spectrum of MDA functionality. A positive correlation was identified between MDA dysfunction and the resting-state functional connectivity (RSFC) between the left ventrolateral periaqueductal gray (vlPAG) and the right temporal pole of the superior temporal gyrus. Conversely, a negative correlation was observed between MDA dysfunction and the RSFC of the right vlPAG with the right superior parietal lobule. Additionally, MDA dysfunction exhibited a negative association with the RSFC between the dorsomedial PAG (dmPAG) and the right inferior parietal lobule. These findings may indicate that the specific signal from a distended bladder is blocked in the PAG and its functional connectivity with the executive function, attention, and default mode networks, ultimately leading to impaired arousal and bladder control. This revelation underscores potential neural targets for future therapeutic interventions.

Brain carbon monoxide can suppress the rat micturition reflex through brain γ-aminobutyric acid receptors.

OBJECTIVES: To investigate roles of brain carbon monoxide (CO), an endogenous gasotransmitter, in regulation of the rat micturition reflex. METHODS: In urethane-anesthetized (0.8 g/kg, ip) male rats, evaluation of urodynamic parameters was started 1 h before intracerebroventricular administration of CORM-3 (CO donor) or ZnPP (non-selective inhibitor of heme oxygenase, a CO producing enzyme) and continued for 2 h after the administration. We also investigated effects of centrally pretreated SR95531 (GABAA receptor antagonist) or SCH50911 (GABAB receptor antagonist) on the CORM-3-induced response. RESULTS: CORM-3 significantly prolonged intercontraction intervals (ICIs) without changing maximal voiding pressure (MVP), while ZnPP significantly shortened ICI and reduced single-voided volume and bladder capacity without affecting MVP, post-voided residual volume, or voiding efficiency. The ZnPP-induced ICI shortening was reversed by CORM-3. The CORM-3-induced ICI prolongation was significantly attenuated by centrally pretreated SR95531 or SCH50911, respectively. CONCLUSIONS: Brain CO can suppress the rat micturition reflex through brain γ-aminobutyric acid (GABA) receptors.

Reflex voiding in rat occurs at consistent bladder volume regardless of pressure or infusion rate.

AIMS: The central nervous system (CNS) regulates lower urinary tract reflexes using information from sensory afferents; however, the mechanisms of this process are not well known. Pressure and volume were measured at the onset of the guarding and micturition reflexes across a range of infusion rates to provide insight into what the CNS is gauging to activate reflexes. METHODS: Female Sprague Dawley rats were anesthetized with urethane for open outlet cystometry. A set of 10 infusion rates (ranging 0.92-65.5 mL/h) were pseudo-randomly distributed across 30 single-fill cystometrograms. Bladder pressure and external urethral sphincter electromyography were used for the determination of the onset of the micturition and guarding reflexes, respectively. The bladder volume at the onset of both reflexes was estimated from the total infusion rate during a single fill. RESULTS: In response to many single-fill cystometrograms, there was an increased volume the bladder could store without a significant increase in pressure. Volume was adjusted for this effect for the analysis of how pressure and volume varied with infusion rate at the onset of the micturition and guarding reflexes. In 25 rats, the micturition reflex was evoked at similar volumes across all infusion rates, whereas the pressure at micturition reflex onset increased with increasing infusion rates. In 11 rats, the guarding reflex was evoked at similar pressures across infusion rates, but the volume decreased with increasing infusion rates. CONCLUSIONS: These results suggest that the CNS is interpreting volume from the bladder to activate the micturition reflex and pressure from the bladder to activate the guarding reflex.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

Corticotropin-Releasing Hormone from the Pontine Micturition Center Plays an Inhibitory Role in Micturition.

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. These effects were eliminated by CRH-receptor 1 antagonist pretreatment. Optogenetic inhibition of CRH-PMC neurons led to an altered voiding phenotype characterized by more frequent voids and smaller voided volumes. Last, in a cyclophosphamide cystitis model of bladder overactivity, optogenetic activation of CRH-PMC neurons returned the voiding pattern to normal. Collectively, our findings demonstrate that CRH from PMC spinal-projecting neurons has an inhibitory function on micturition and is a potential therapeutic target for human disease states, such as voiding postponement, urinary retention, and underactive or overactive bladder.SIGNIFICANCE STATEMENT The pontine micturition center (PMC), which is a major regulator of volitional micturition, is neurochemically heterogeneous, and excitatory neurotransmission derived from PMC neurons is thought to mediate the micturition reflex. In the present study, using optogenetic manipulation of CRH-containing neurons in double-transgenic mice, we demonstrate that CRH, which is prominent in PMC-spinal projections, has an inhibitory function on volitional micturition. Moreover, engaging this inhibitory function of CRH can ameliorate bladder hyperexcitability induced by cyclophosphamide in a model of cystitis. The data underscore CRH as a novel target for the treatment of voiding dysfunctions, which are highly prevalent disease processes in children and adults.

Stimulation of brain corticotropin-releasing factor receptor type1 facilitates the rat micturition via brain glutamatergic receptors.

Corticotropin-releasing factor (CRF), a representative stress-related neuropeptide, in the central nervous system reportedly both facilitates and suppresses the micturition, therefore, roles of central CRF in regulation of the micturition are still controversial. In this study, we investigated (1) effects of intracerebroventricularly (icv)-administered CRF on the micturition, and (2) brain CRF receptor subtypes (CRFR1/CRFR2) and glutamatergic receptors (NMDA/AMPA subtypes) involved in the CRF-induced effects in male Wistar rats under urethane anesthesia. Intercontraction intervals (ICI), and maximal voiding pressure (MVP), were evaluated by continuous cystometry 45 min before CRF administration or intracerebroventricular pretreatment with other drugs as follows and 3 h after CRF administration. Single-voided volume (Vv), post-voiding residual volume (Rv), bladder capacity (BC), and voiding efficiency (VE) were evaluated by single cystometry 60 min before CRF administration and 60-120 min after the administration. Icv-administered CRF reduced ICI, Vv, and BC without changing MVP, Rv, or VE. The CRF-induced ICI reduction was attenuated by icv-pretreated CP154526 (CRFR1 antagonist), MK-801 (NMDA receptor antagonist), and DNQX (AMPA receptor antagonist), but not by K41498 (CRFR2 antagonist). These results indicate that stimulation of brain CRFR1 can be involved in facilitation of the rat micturition via brain NMDA/AMPA receptors.

Afferent nerve activity in a mouse model increases with faster bladder filling rates in vitro, but voiding behavior remains unaltered in vivo.

Storage and voiding functions in urinary bladder are well-known, yet fundamental physiological events coordinating these behaviors remain elusive. We sought to understand how voiding function is influenced by the rate at which the bladder fills. We hypothesized that faster filling rates would increase afferent sensory activity and increase micturition rate. In vivo, this would mean animals experiencing faster bladder filling would void more frequently with smaller void volumes. To test this hypothesis, we measured afferent nerve activity during different filling rates using an ex vivo mouse bladder preparation and assessed voiding frequency in normally behaving mice noninvasively (UroVoid). Bladder afferent nerve activity depended on the filling rate, with faster filling increasing afferent nerve activity at a given volume. Voiding behavior in vivo was measured in UroVoid cages. Male and female mice were given access to tap water or, to induce faster bladder filling rates, water containing 5% sucrose. Fluid intake increased dramatically in mice consuming 5% sucrose. As expected, micturition frequency was elevated in the sucrose group. However, even with the greatly increased rate of urine production, void volumes were unchanged in both genders. Although faster filling rates generated higher afferent nerve rates ex vivo, this did not translate into more frequent, smaller-volume voids in vivo. This suggests afferent nerve activity is only one factor contributing to the switch from bladder filling to micturition. Together with afferent nerve activity, higher centers in the central nervous system and the state of arousal are likely critical to coordinating the micturition reflex.

The effect of amino acids on the bladder cycle: a concise review.

The human bladder maintains a cycle of filling, storing, and micturating throughout an individual's lifespan. The cycle relies on the ability of the bladder to expand without increasing the intravesical pressure, which is only possible with the controlled relaxation of well-complaint muscles and the congruously organized construction of the bladder wall. A competent bladder outlet, which functions in a synchronous fashion with the bladder, is also necessary for this cycle to be completed successfully without deterioration. In this paper, we aimed to review the contemporary physiological findings on bladder physiology and examine the effects of amino acids on clinical conditions affecting the bladder, with special emphasis on the available therapeutic evidence and possible future roles of the amino acids in the treatment of the bladder-related disorders.

Micturition-triggered severe headache associated with bladder paraganglioma: A case report.

BACKGROUND: Paragangliomas are rare neuroendocrine tumors, especially in the bladder. Although many paragangliomas are non-functional, functioning paragangliomas present with many non-specific signs and symptoms, such as hypertension and headache, complicating their diagnosis. Here, we report a case of micturition-induced severe headache associated with a bladder paraganglioma.Case description: This report describes a severe headache disorder triggered by micturition and associated with a bladder paraganglioma in a middle-aged woman. Her pain occurred consistently after micturition, beginning from the left side of the nose and gradually extended to the forehead and the parietal and occipital regions. The headaches lasted 5-10 min. Removal of the paraganglioma completely eliminated the patient's pain syndrome. CONCLUSION: This case elucidates the association between micturition-triggered headaches and bladder paragangliomas. The presence of a post-micturition severe headache should suggest the possibility of a bladder paraganglioma.

The relationship between bladder storage function and frequent micturition after TURP.

PURPOSE: To investigate the relationship between preoperative bladder function and frequent micturition after transurethral resection of prostate in patients with benign prostatic hyperplasia. METHODS: We retrospectively included 80 eligible patients aged 54-87 years (mean age 69.8 years) who underwent transurethral resection of the prostate at our hospital from January 2019 to October 2021. Patients were divided into detrusor overactivity positive and negative groups, and according to bladder compliance, they were divided into: low (G1), normal (G2), and high (G3) bladder compliance groups. RESULTS: The incidence and score of postoperative frequent micturition in the detrusor overactivity positive group were higher than those in the detrusor overactivity negative group. The incidence and score of postoperative frequent micturition in the low bladder compliance group were higher than those in the normal and high bladder compliance groups. There was no significant difference in the score of frequent micturition between the normal and high bladder compliance groups. Multivariate logistic regression analysis indicated that frequent micturition was significantly correlated with detrusor overactivity, bladder compliance, maximum cystometric capacity, and maximum flow rate. CONCLUSION: This study confirmed that patients with abnormal bladder storage functions (detrusor instability and low bladder compliance) before transurethral resection of the prostate were likely to have frequent and severe urination after transurethral resection of the prostate. Therefore, preoperative urodynamic examination to evaluate the urinary storage function of patients with benign prostatic hyperplasia is of great significance to predict the occurrence and degree of postoperative frequent micturition.

Defining urge as an uncontrolled micturition explains pathogenesis, informs cure and helps solve the burgeoning OAB crisis.

BACKGROUND: Parallel with the demographic ageing crisis, is a disabling overactive bladder (OAB) crisis (urgency/frequency/nocturia), 30% prevalence in older women, pathogenesis stated as unknown and, according to some learned societies, incurable. HYPOTHESIS/AIMS: To review International Continence Society and Integral System paradigms to test our thesis that OAB per se is not a pathological condition, rather, a prematurely activated uncontrolled micturition; pathogenesis being anatomical damage in a nonlinear feedback control system comprising cortical and peripheral (muscle/ligament) components. METHODS: We examined studies from basic science, anatomy, urodynamics, ultrasonic and video xrays, ligament repairs, from which we created a nonlinear binary model of bladder function. We applied a Chaos Theory feedback equation, Xnext = Xc(1 - X) to test our hypothesis against existing concepts and hypotheses for OAB pathogenesis. RESULTS: The bladder has ONLY two modes, EITHER closed OR open (micturition). Closure is reflexly controlled cortically and peripherally: muscles contracting against ligaments stretch the vagina to suppress afferent signals to micturate from urothelial stretch receptors. "OAB" can be caused by anatomical damage anywhere in the model, by childbirth or age-weakened ligaments, which can be repaired to cure all three OAB symptoms. Urodynamic "DO" graphs are interpreted anatomically and by the feedback equation. CONCLUSION: OAB is in crisis. Our thesis of OAB as an uncontrolled micturition from anatomical defects in the bladder control system provides fresh directions for further development of new treatments, nonsurgical and surgical, to help break the crisis and bring hope and cure to 600 million women sufferers.

An anatomical pathogenesis of lower urinary tract definitions from the 2002 ICS report symptoms, conditions, syndromes, urodynamics.

AIM: To present an anatomical pathogenesis parallel with the 2002 International Continence Society Lower Urinary Tract (LUTS) definitions standardization Report 2002. METHODS: Each LUTS section is discussed using the same numbers as the Report. RESULTS: Normal function Bladder control is binary, with two reflexes alternating, either closure (dominant) or open (micturition), with the same cortical and peripheral components: three directional muscle forces contracting against pubourethral (PUL) and uterosacral (USL) ligaments for closure, two against uterosacral ligaments for micturition. Dysfunction OAB symptoms reflect a prematurely activated micturition; PUL/USL weakness prevents muscle forces from controlling afferent urothelial emptying signals. Stress urinary incontinence is a consequence of weak PULs allowing posterior muscle forces to open the urethra during effort. Lax USLs weaken contractile force of the posterior urethral opening vectors, so detrusor has to contract against an unopened urethra. This is experienced as "obstructive micturition." CONCLUSIONS: Anatomical analysis indicates the ICS definitions are fundamentally sound, except for "OAB" which implies detrusor causation. Minor changes, OAB to "overactivated" bladder allow causation outside of bladder. This construct supports OAB and its component symptoms as a syndrome, as intuited by the Committee, (albeit as a prematurely activated micturition), retains the acronym, explains OAB cure by ligament repair, and incontinence pathogenesis from two post-2002 syndromes which need an addition to the definitions, Posterior Fornix Syndrome (of which OAB is a component) and Tethered Vagina Syndrome, which is the basis for skin-grafting cure of the 30%-50% of women who continue leaking urine massively after successful obstetric fistula closure.

Altered bladder-related brain network in multiple sclerosis women with voiding dysfunction.

OBJECTIVES: A number of neurourology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamic study (UDS)/functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥6 months and symptomatic voiding phase neurogenic lower urinary tract dysfunction (NLUTD) underwent UDS/fMRI evaluation with a task of bladder filling/emptying that was repeated three to five times. We quantitatively compared their FC within 17 bladder-related brain regions during two UDS phases: "strong desire to void" and "(attempt at) voiding initiation." RESULTS: At "strong desire to void," the healthy group showed significantly stronger FC in regions involved in bladder filling and suppression of voiding compared to the patient group. These regions included the bilateral anterior cingulate cortex, right supplementary motor area, and right middle frontal gyrus. During "(attempt at) voiding initiation," healthy subjects exhibited stronger FC in the right inferior frontal gyrus compared to MS patients. CONCLUSION: Our study offers a new way to identify alterations in the neural mechanisms underlying NLUTD and provides potential targets for clinical interventions (such as cortical neuromodulation) aimed at restoring bladder functions in MS patients.

Clinical effect of micturition interruption exercise on urinary incontinence after radical prostatectomy.

PURPOSE: To explore the effectiveness of micturition interruption exercise in improving the incidence of urinary incontinence after radical prostatectomy. MATERIALS AND METHODS: With a retrospective case-control study, 96 patients admitted in the Second Affiliated Hospital of Zhejiang Chinese Medical University from August 2014 to August 2020 and underwent radical prostatectomy were collected as the subjects. Those patients who used micturition interruption exercise (n = 48) were set as the therapy group, and the control group was collected according to the ratio of 1:1; the patients used Kegel exercise (n = 48) to compare the rehabilitation of urinary incontinence in patients and the effect of training compliance on rehabilitation. RESULTS: The recovery time of urinary incontinence in the therapy group was significantly shorter than that of the control group. In the therapy group, 83.3% of patients with training compliance reached an average or above, while the control group only accounted for 58.3%. International Consultation on Incontinence Questionnaire Short-Form score of the therapy group was lower than that of the control group after surgery. Spearman analysis suggests that there is a negative correlation between the postoperative urinary incontinence recovery time and compliance with the micturition interruption exercise. CONCLUSIONS: Micturition interruption exercise could not only improve the compliance of patients with exercise, but also significantly shorten the recovery time of urinary incontinence after radical prostatectomy.

Dropped abdominal pressure at void in women.

INTRODUCTION AND HYPOTHESIS: "Dropped pabd at void" occurs when pabd decreases below the previous resting pressure during voiding time. We sought clinical factors associated with this phenomenon and evaluated whether its correction modifies the urodynamic diagnosis. METHODS: Retrospective cross-sectional study of non-neurological consecutive symptomatic women. The following definitions were used: "dropped pabd at void": decrease in pabd at Qmax ≥ 5 cmH2O; bladder outflow obstruction (BOO) (pdetQmax ≥ 25 cmH2O + Qmax ≤ 12 ml/s and female BOO index (pdetQmax - 2.2*Qmax) > 18; "low detrusor contraction strength": PIP1 (pdetQmax + Qmax) < 30. In patients with "dropped pabd at void", pdetQmax was corrected. RESULTS: A total of 360 women were analyzed. Ninety-five percent of the women had a variation in pabd at Qmax between -13 and 53 cmH2O. "Dropped pabd at void" was found in 100 women (27.8%). History of stress urinary incontinence (SUI) surgery was significantly higher (p = 0.016) and symptoms of mixed urinary incontinence were significantly lower (p = 0.030) in patients with "dropped pabd at void". On multivariate analysis only the history of SUI surgery maintained its significance (OR = 1.787 [95% CI: 1.058, 3.017], p = 0.030). When correcting pdetQmax in women with "dropped pabd at void", 2 or 5 patients lost BOO diagnosis (depending on how it was diagnosed) and 7 patients gained a "low detrusor contraction strength" diagnosis. CONCLUSIONS: Approximately one-quarter of women had "dropped pabd at void", which was associated with a history of SUI surgery. Correction of pdetQmax would lead to a 2.5% to 3.33% diagnostic modification.

Micturition in the toilet compared with bedpan in laboring Nulliparas: a randomized controlled trial.

BACKGROUND: Bladder overdistension in labor may lead to prolonged postpartum urinary retention. We hypothesized that nulliparas mobilizing to toilet is more likely to achieve satisfactory micturition. METHODS: One hundred sixteen (58 in each arm) term nulliparas in labor with filled bladders were randomized to mobilizing to the toilet or using bedpan to micturate. Primary outcome was satisfactory micturition defined as ultrasound derived post-void bladder volume < 150 ml. Following unsatisfactory micturition, participants crossover to the opposed intervention. Participants were catheterized if after crossover, residual bladder volume was ≥250 ml. RESULTS: Satisfactory micturition rates were 55/58 (95%) vs. 43/58 (74%) RR 1.28 95%CI 1.08-1.51 NNTb 4.8 95%CI 3.0-12.4 P = 0.008, failure to micturate 1/58 (2%) vs. 8/58 (14%) RR 0.13 95%CI 0.02-0.97 NNTb 8.3 95%CI 4.6-38.7 P = 0.047. After cross over following unsatisfactory bladder voiding, satisfactory micturition rates were 0/3 (0%) vs 13/15 (87%) P = 0.024, bladder catheterization rates were 3/58 (5%) vs. 2/58 (4%) RR 95%CI 1.5 (0.26-8.65) P = 0.648, maternal satisfaction with allocated intervention 55/58 (95%) vs. 9/58 (16%) RR 95%CI 6.1 (3.3-11.2) NNTb 95%CI 1.3 (1.1-1.5) P <  0.0001 and preference for mobilizing to the toilet if micturition was needed again during labor 55/58 (95%) vs. 53/58 (92%) for mobilizing to the toilet compared to bedpan use arms respectively. Labor and neonatal outcomes were similar. CONCLUSION: Satisfactory micturition was more frequently achieved with mobilization to the toilet than bedpan use. Women in both arms overwhelmingly prefer to mobilize to the toilet to urinate. TRIAL REGISTRATION: This study was registered with ISRCTN on 17/07/2019 with trial identification number: ISRCTN17787339 . First participant was recruited on 31/07/2019. The last patient was recruited on 18/12/2019.

G protein-coupled estrogen receptor (GPER/GPR30) levels in pelvic floor muscles and its association with estrogen status in female rabbits.

Objective: To assess the relative expression of the G-protein coupled estrogen receptor (GPER) in the bulbospongiosus (Bsm) and pubococcygeus (Pcm) muscles in control, ovariectomized (OVX), and OVX with estradiol benzoate supplementation (OVX + EB) rabbits.Methods: We used tissues from C, 1-month OVX, and OVX plus 15-day EB implanted (OVX + EB) groups. The GPER expression was evaluated by Western blot and immunohistochemistry for both Bsm and Pcm. Results: Both muscles showed a GPER immunoreactivity in blood vessels, inside myofibers next to myonuclei, and in polymorphonuclear cells. Four-week ovariectomy did not modify the GPER expression in the Bsm and Pcm, but two-week estradiol benzoate increased it in the latter muscle alone.Conclusions: We demonstrated that the Bsm and Pcm of female rabbits express GPER. High serum estradiol levels elevate GPER relative expression in the Pcm alone. The present study supports the remarkable estrogen sensitivity of the Pcm.