Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype.

INTRODUCTION AND OBJECTIVE: Interstitial cystitis and bladder pain syndrome (IC/BPS) presents with symptoms of debilitating bladder pain and is typically a diagnosis of exclusion. The cystoscopic detection of Hunner's lesions increases the likelihood of detecting tissue inflammation on bladder biopsy and increases the odds of therapeutic success with anti-inflammatory drugs. However, the identification of this subgroup remains challenging with the current lack of surrogate biomarkers of IC/BPS. On the path towards identifying biomarkers of IC/BPS, we modeled the dynamic evolution of inflammation in an experimental IC/BPS rodent model using computational biological network analysis of inflammatory mediators (cytokines and chemokines) released into urine. The use of biological network analysis allows us to identify urinary proteins that could be drivers of inflammation and could therefore serve as therapeutic targets for the treatment of IC/BPS. METHODS: Rats subjected to cyclophosphamide (CYP) injection (150 mg/kg) were used as an experimental model for acute IC/BPS (n = 8). Urine from each void was collected from the rats over a 12-h period and was assayed for 13 inflammatory mediators using Luminex™. Time-interval principal component analysis (TI-PCA) and dynamic network analysis (DyNA), two biological network algorithms, were used to identify biomarkers of inflammation characteristic of IC/BPS over time. RESULTS: Compared to vehicle-treated rats, nearly all inflammatory mediators were elevated significantly (p < 0.05) in the urine of CYP treated rats. TI-PCA highlighted that GRO-KC, IL-5, IL-18, and MCP-1 account for the greatest variance in the inflammatory response. At early time points, DyNA indicated a positive correlation between IL-4 and IL-1ß and between TNF-α and IL-1ß. Analysis of TI-PCA and DyNA at later time points showed the emergence of IL-5, IL-6, and IFNγ as additional key mediators of inflammation. Furthermore, DyNA network complexity rose and fell before peaking at 9.5 h following CYP treatment. This pattern of inflammation may mimic the fluctuating severity of inflammation associated with IC/BPS flares. CONCLUSIONS: Computational analysis of inflammation networks in experimental IC/BPS analysis expands on the previously accepted inflammatory signatures of IC by adding IL-5, IL-18, and MCP-1 to the prior studies implicating IL-6 and GRO as IC/BPS biomarkers. This analysis supports a complex evolution of inflammatory networks suggestive of the rise and fall of inflammation characteristic of IC/BPS flares.

Pharmacologic Management of Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as persistent or chronic discomfort perceived to be related to the urinary bladder accompanied by urinary urgency or frequency. Pharmacotherapies used to treat IC/BPS include oral and intravesical agents. Oral therapies include amitriptyline, hydroxyzine, cyclosporine A, and pentosan polysulfate sodium (PPS), although the recent finding of pigmented maculopathy with chronic PPS is very concerning and must be discussed with patients, many of whom will choose to either come off this medicine or not even start it. Certolizumab pegol is a pharmacologic therapy that is currently in clinical development for treatment of IC/BPS symptoms.

Cost-effectiveness of behavioral and pelvic floor muscle therapy combined with midurethral sling surgery vs surgery alone among women with mixed urinary incontinence: results of the Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence randomized trial.

BACKGROUND: Urinary incontinence is prevalent among women, and it has a substantial economic impact. Mixed urinary incontinence, with both stress and urgency urinary incontinence symptoms, has a greater adverse impact on quality of life and is more complex to treat than either stress or urgency urinary incontinence alone. Studies evaluating the cost-effectiveness of treating both the stress and urgency urinary incontinence components simultaneously are lacking. OBJECTIVE: Cost-effectiveness was assessed between perioperative behavioral and pelvic floor muscle therapies combined with midurethral sling surgery and midurethral sling surgery alone for the treatment of women with mixed urinary incontinence. The impact of baseline severe urgency urinary incontinence symptoms on cost-effectiveness was assessed. STUDY DESIGN: This prospective economic evaluation was performed concurrently with the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence randomized trial that was conducted from October 2013 to April 2016. Participants included 480 women with moderate-to-severe stress and urgency urinary incontinence symptoms and at least 1 stress urinary incontinence episode and 1 urgency urinary incontinence episode on a 3-day bladder diary. The primary within-trial analysis was from the healthcare sector and societal perspectives, with a 1-year time horizon. Costs were in 2019 US dollars. Effectiveness was measured in quality-adjusted life-years and reductions in urinary incontinence episodes per day. Incremental cost-effectiveness ratios of combined treatment vs midurethral sling surgery alone were calculated, and cost-effectiveness acceptability curves were generated. Analysis was performed for the overall study population and subgroup of women with Urogenital Distress Inventory irritative scores of ≥50th percentile. RESULTS: The costs for combined treatment were higher than the cost for midurethral sling surgery alone from both the healthcare sector perspective ($5100 [95% confidence interval, $5000-$5190] vs $4470 [95% confidence interval, $4330-$4620]; P<.01) and the societal perspective ($9260 [95% confidence interval, $8590-$9940] vs $8090 [95% confidence interval, $7630-$8560]; P<.01). There was no difference between combined treatment and midurethral sling surgery alone in quality-adjusted life-years (0.87 [95% confidence interval, 0.86-0.89] vs 0.87 [95% confidence interval, 0.86-0.89]; P=.90) or mean reduction in urinary incontinence episodes per day (-4.76 [95% confidence interval, -4.51 to 5.00] vs -4.50 [95% confidence interval, -4.25 to 4.75]; P=.13). When evaluating the overall study population, from both the healthcare sector and societal perspectives, midurethral sling surgery alone was superior to combined treatment. The probability that combined treatment is cost-effective compared with midurethral sling surgery alone is ≤28% from the healthcare sector and ≤19% from the societal perspectives for a willingness-to-pay value of ≤$150,000 per quality-adjusted life-years. For women with baseline Urogenital Distress Inventory irritative scores of ≥50th percentile, combined treatment was cost-effective compared with midurethral sling surgery alone from both the healthcare sector and societal perspectives. The probability that combined treatment is cost-effective compared with midurethral sling surgery alone for this subgroup is ≥90% from both the healthcare sector and societal perspectives, at a willingness-to-pay value of ≥$150,000 per quality-adjusted life-years. CONCLUSION: Overall, perioperative behavioral and pelvic floor muscle therapies combined with midurethral sling surgery was not cost-effective compared with midurethral sling surgery alone for the treatment of women with mixed urinary incontinence. However, combined treatment was of good value compared with midurethral sling surgery alone for women with baseline severe urgency urinary incontinence symptoms.

Sexual Activity and Dyspareunia 1 Year After Surgical Repair of Pelvic Organ Prolapse.

OBJECTIVE: To describe sexual activity and risks for dyspareunia after pelvic organ prolapse surgery. METHODS: This was a secondary analysis of data from four randomized trials conducted between 2002 and 2018. Standard assessments and validated measures of sexual function were assessed at baseline and at 12 months postoperatively. Anterior apical surgeries were grouped by approach: transvaginal native tissue repairs, transvaginal mesh or graft-augmented repairs, and abdominal sacrocolpopexy. Additional surgeries, which included posterior repair, hysterectomy, and slings, were analyzed. Bivariate analyses and logistic regression models identified risk factors for postoperative dyspareunia. RESULTS: Of the 1,337 women enrolled in the trials, 932 had sufficient outcome data to determine dyspareunia status. Of these before surgery, 445 (47.8%) were sexually active without dyspareunia, 89 (9.6%) were sexually active with dyspareunia, 93 (10.0%) were not sexually active owing to fear of dyspareunia, and 305 (32.7%) were not sexually active for other reasons. At 12 months, dyspareunia or fear of dyspareunia was present in 63 of 627 (10.0%); occurred de novo in 17 of 445 (3.8%) and resolved in 136 of 182 (74.7%). Multivariable regression demonstrated baseline dyspareunia as the only factor associated with postoperative dyspareunia (adjusted odds ratio 7.8, 95% CI 4.2-14.4). No other factors, including surgical approach, were significantly associated with postoperative dyspareunia. Too few had de novo dyspareunia to perform modeling. CONCLUSION: Dyspareunia is common in one in five women before undergoing prolapse surgery. Surgical repair resolves dyspareunia in three out of four women with low rates of de novo dyspareunia at less than 4%. Preoperative dyspareunia appears to be the only predictor of postoperative dyspareunia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00065845, NCT00460434, NCT00597935, and NCT01802281.

Deciding Our Future: Consensus Conference Summary Report.

OBJECTIVES: There are few quality measures that allow for optimization of care for pelvic organ prolapse (POP). In coordination with the American Urogynecologic Society (AUGS), a prior group agreed upon health care provider-reported data elements that are important for large-scale quality measurement. The primary objective was to review existing patient-reported outcome (PRO) measurement tools for POP and consider where improvements are needed for inclusion in a quality measurement tool. A secondary objective was to discuss enhanced strategies to improve the quality of care for women with mesh complications. METHODS: The AUGS Scientific Committee convened a 1-day meeting titled "Deciding our Future: Consensus Conference on Prolapse Outcomes and Best Practices for Mesh Complications." Speakers discussed the current state of POP outcome measurement and meaningful ways of measuring and improving quality. Furthermore, past and future work for standardization of care regarding mesh complications was discussed. RESULTS: Conference participants included invited speakers, representatives from AUGS and partner societies, 5 patient representatives from the AUGS Patient Advisory Committee, and 38 registered participants from academic institutions, community practices, and industry. Participants developed a roadmap for incorporating PROs into a national POP quality improvement registry. Participants also discussed important gaps in our knowledge of treatment of mesh complications and previewed proposed terminology and treatment algorithms. CONCLUSIONS: Using appropriate methodology, existing PRO measurement tools can be collapsed into one concise tool for POP quality measurement. Over the next year, work will continue toward this goal. Proposed updates to mesh terminology and treatment algorithms will be published separately.

Urethral dysfunction and therapeutic effects of a PDE 5 inhibitor (tadalafil) in a rat model of detrusor underactivity induced by pelvic nerve crush injury.

AIMS: The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. METHODS: Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. RESULTS: PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. CONCLUSIONS: PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.

Gaining the patient perspective on pelvic floor disorders' surgical adverse events.

BACKGROUND: The Institute for Healthcare Improvement defines an adverse event as an unintended physical injury resulting from or contributed to by medical care that requires additional monitoring, treatment, or hospitalization or that results in death. The majority of research has focused on adverse events from the provider's perspective. OBJECTIVE: The objective of this qualitative study was to describe patient perceptions on adverse events following surgery for pelvic floor disorders. STUDY DESIGN: Women representing the following 3 separate surgical populations participated in focus groups: (1) preoperative (women <12 weeks prior to surgery); (2) short-term postoperative (women up to 12 weeks after surgery); and (3) long-term postoperative (women 1-5 years after surgery). Deidentified transcripts of audio recordings were coded and analyzed with NVivo 10 software to identify themes, concepts, and adverse events. Women were asked to rank patient-identified and surgeon-identified adverse events in order of perceived severity. RESULTS: Eighty-one women participated in 12 focus groups. Group demographics were similar between groups, and all groups shared similar perspectives regarding surgical expectations. Women commonly reported an unclear understanding of their surgery and categorized adverse events such as incontinence, constipation, nocturia, and lack of improvement in sexual function as very severe, ranking these comparably with intensive care unit admissions or other major surgical complications. Women also expressed a sense of personal failure and shame if symptoms recurred. CONCLUSION: Women consider functional outcomes such as incontinence, sexual dysfunction, and recurrence of symptoms as severe adverse events and rate them as similar in severity to intensive care unit admissions and death.

Recent Developments in Imaging in BPS/IC.

Purpose of review: In this review, the current literature of imaging of bladder pain syndrome and interstitial cystitis (BPS/IC) will be addressed. Topics include BPS/IC, cystoscopy, computed tomography, and magnetic resonance image (MRI). Recent findings: There are no randomized clinical trials on imaging of BPS/IC. Recently, contrast-enhanced MRI could detect the brain alterations and the changes in bladder permeability, and detection of the latter is enhanced by intravesical injection of contrast agents. Summary: MRI could advance the understanding of pathological changes in the brain and the bladder of BPS/IC patients. Especially, contrast-enhanced MRI has a potential to become a diagnostic tool although more evidences are necessary for clarifying the efficacy.

Effect of TRPV4 activation in a rat model of detrusor underactivity induced by bilateral pelvic nerve crush injury.

AIMS: To produce an animal model of peripheral neurogenic detrusor underactivity (DU) and to evaluate the effect of TRPV4 receptor activation in this DU model. METHODS: In female Sprague-Dawley rats, bilateral pelvic nerve crush (PNC) was performed by using sharp forceps. After 10 days, awake cystometrograms (CMG) were recorded in sham and PNC rats. A TRPV4 agonist (GSK 1016790A) with or without a TRPV4 antagonist (RN1734) were administered intravesically and CMG parameters were compared before and after drug administration in each group. The TRPV4 transcript level in the bladder mucosa and histological changes were also evaluated. RESULTS: In CMG, PNC rats showed significant increases in intercontraction intervals (ICI), number of non-voiding contractions (NVCs), baseline pressure, threshold pressure, bladder capacity, voided volumes, and post-void residual (PVR) compared to sham rats. Contraction amplitude and voiding efficiency were significantly decreased in PNC rats. In PNC rats, intravesical application of GSK1016790A (1.5 µM) significantly decreased ICI, bladder capacity, voided volume, and PVR without increasing NVCs, and these effects were blocked by RN1734 (5.0 µM). In contrast, 1.5 µM GSK1016790A had no significant effects on CMG parameters in normal rats. TRPV4 expression within the bladder mucosa of PNC rats was increased in association with urothelial thickening. CONCLUSIONS: Rats with bilateral PNC showed characteristics of DU, and this model seems appropriate for further evaluation of peripheral neurogenic mechanisms of DU. Also, TRPV4 receptors, the activation of which reduced bladder capacity and PVR, could be a target for DU treatment.

MicroRNAs as potential biomarkers to predict the risk of urinary retention following intradetrusor onabotulinumtoxin-A injection.

AIMS: MicroRNAs (miRs) control post-transcriptional gene expression, and this is relevant in understanding better chronic diseases and treatment outcomes. The role of miRs in the pathology and treatment outcomes of overactive bladder (OAB) is unknown. In this study, we assessed the differential expression of miRs in OAB patients responding with either normal or elevated post-void residual volumes (PVRs) ≥200 mL following intradetrusor injection of onabotulinumtoxin-A (onaBoNT-A). METHODS: Female OAB patients refractory to OAB drugs were consented for this study. Cystoscopic-guided punch bladder biopsy was obtained at the time of injection of onaBoNT-A 100 units. The expression of 13 miR species, selected for their known effect on neurotrophin expression and smooth muscle function, was measured. PVRs and urine nerve growth factor (NGF) levels were measured at baseline and at the follow-up visit. RESULTS: Fourteen patients with mean age of 66 years were consented. Of these patients, nine maintained PVRs <200 mL after onaBoNT-A injection to comprise the low PVR group. The other five patients with PVRs ≥200 mL comprised the high PVR group. The expression of miR221 and miR125b was upregulated by 11- and 2-fold, respectively, in patients who responded with low PVRs after onaBoNT-A (P < 0.05). Urine NGF levels at baseline were not different between the two groups. CONCLUSIONS: This study suggests that deficiency in the pretreatment expression of miR221 and miR125b may predispose OAB patients to high PVRs following intradetrusor onaBoNT-A. Additional studies are needed to better understand the role of miRs in OAB.

BDNF overexpression in the bladder induces neuronal changes to mediate bladder overactivity.

Elevated levels of brain-derived neurotrophic factor (BDNF) in urine of overactive bladder (OAB) patients support the association of BDNF with OAB symptoms, but the causality is not known. Here, we investigated the functionality of BDNF overexpression in rat bladder following bladder wall transfection of either BDNF or luciferase (luciferase) transgenes (10 µg). One week after transfection, BDNF overexpression in bladder tissue and elevation of urine BDNF levels were observed together with increased transcript of BDNF, its cognate receptors (TrkB and p75NTR), and downstream PLCγ isoforms in bladder. BDNF overexpression can induce the bladder overactivity (BO) phenotype which is demonstrated by the increased voiding pressure and reduced intercontractile interval during transurethral open cystometry under urethane anesthesia. A role for BDNF-mediated enhancement of prejunctional cholinergic transmission in BO is supported by the significant increase in the atropine- and neostigmine-sensitive component of nerve-evoked contractions and upregulation of choline acetyltransferase, vesicular acetylcholine transporter, and transporter Oct2 and -α1 receptors. In addition, higher expression of transient receptor channels (TRPV1 and TRPA1) and pannexin-1 channels in conjunction with elevation of ATP and neurotrophins in bladder and also in L6/S1 dorsal root ganglia together support a role for sensitized afferent nerve terminals in BO. Overall, genomic changes in efferent and afferent neurons of bladder induced by the overexpression of BDNF per se establish a mechanistic link between elevated BDNF levels in urine and dysfunctional voiding observed in animal models and in OAB patients.

Translational approaches to the treatment of benign urologic conditions in elderly women.

PURPOSE OF REVIEW: Stress urinary incontinence, overactive bladder, interstitial cystitis/painful bladder syndrome, and underactive bladder are highly prevalent among elderly women, and have significant impact on quality of life; however, existing treatments are limited and are not always successful for all patients. Researchers are investigating a multitude of new therapies to treat these conditions. This review will summarize the recent literature on investigative therapies for these conditions. RECENT FINDINGS: Multiple new treatments are being developed for lower urinary tract dysfunction. Some of these treatments, including balloon therapy and muscle-derived stem cells for stress urinary incontinence, could provide alternatives to existing therapies. Others require further research before being used in patients, such as pudendal nerve stimulation for overactive bladder and intravesical liposomes for drug delivery in interstitial cystitis/painful bladder syndrome. SUMMARY: Multiple new therapies are being investigated that could provide clinicians with additional tools to treat lower urinary tract disorders in millions of elderly women.

Use of Botulinum Toxin in Urologic Diseases.

OnabotulinumtoxinA (onaBoNTA) is approved by the US Food and Drug Administration for the treatment of urinary incontinence due to neurogenic detrusor overactivity and for the treatment of refractory overactive bladder. As a treatment for benign prostatic hyperplasia, onaBoNTA showed no difference over placebo in recently published studies. In contrast, treating interstitial cystitis/bladder pain syndrome with onaBoNTA has shown efficacy, and the current American Urological Association guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome lists onaBoNTA as fourth-line treatment. This comprehensive review will present all studied applications of onaBoNTA within the lower urinary tract.

Brain-derived neurotrophic factor in urinary continence and incontinence.

Urinary incontinence adversely affects quality of life and results in an increased financial burden for the elderly. Accumulating evidence suggests a connection between neurotrophins, such as brain-derived neurotrophic factor (BDNF), and lower urinary tract function, particularly with regard to normal physiological function and the pathophysiological mechanisms of stress urinary incontinence (SUI) and bladder pain syndrome/interstitial cystitis (BPS/IC). The interaction between BDNF and glutamate receptors affects both bladder and external urethral sphincter function during micturition. Clinical findings indicate reduced BDNF levels in antepartum and postpartum women, potentially correlating with postpartum SUI. Experiments with animal models demonstrate that BDNF is decreased after simulated childbirth injury, thereby impeding the recovery of injured nerves and the restoration of continence. Treatment with exogenous BDNF facilitates neural recovery and the restoration of continence. Serotonin and noradrenaline reuptake inhibitors, used to treat both depression and SUI, result in enhanced BDNF levels. Understanding the neurophysiological roles of BDNF in maintaining normal urinary function and in the pathogenesis of SUI and BPS/IC could lead to future therapies based on these mechanisms.

Complications of vaginal mesh surgery.

PURPOSE OF REVIEW: Mesh used for slings and pelvic organ prolapse (POP) repair has resulted in increased efficacy. Yet, the benefits of a more durable repair must be weighed against such risks as vaginal mesh extrusion and erosion and increased dyspareunia, and pelvic pain. We review the current literature on complications seen with the use of vaginal mesh for both stress urinary incontinence and POP. RECENT FINDINGS: The use of mesh in midurethral slings results in similar efficacy but less morbidity compared with nonmesh sling techniques. The use of mesh in abdominal sacrocolpopexy may result in lower rates of mesh complications compared with transvaginal mesh prolapse repairs. In 2011, the Food and Drug Administration issued an updated safety communication stating that serious complications associated with transvaginal mesh for POP repair are not rare. Yet, certain patients do benefit from the use of transvaginal mesh for POP repair. SUMMARY: Better-controlled data are needed to answer questions regarding outcomes, complications, and quality of life after transvaginal mesh prolapse procedures. The surgeon and the patient must have a proper informed consent discussion about the risks, benefits, alternatives, and indications for the use of mesh.

Central compartment and apical defect repair using synthetic mesh.

Pelvic organ prolapse is an increasingly common condition for women that has been challenging to treat due to high recurrence rates after surgical repair. The introduction of mesh-augmented prolapse repairs as a means to achieve more robust repairs had great initial promise. As more data emerge on outcomes and novel mesh complications, the when and where of mesh augmentation has become much less clear. This article reviews the relevant literature on the use of mesh in central and apical repairs. This includes a detailed look at the available data for vaginal mesh kits and several recent trials comparing mesh kits to traditional repairs. The article ends with a discussion of the recent U.S. Food and Drug Administration (FDA) safety communication on the use of transvaginal mesh in pelvic organ prolapse and the authors' views of how practice may change in this new environment.

Selective management of the urethra at time of pelvic organ prolapse repair: an assessment of postoperative incontinence and patient satisfaction.

PURPOSE: Management of the urethra in women without stress urinary incontinence during pelvic organ prolapse repair can be approached selectively or with a prophylactic suburethral sling. We report on patient satisfaction and outcomes in patients who underwent selective urethral management during pelvic organ prolapse repair. MATERIALS AND METHODS: Patients undergoing repair of advanced apical and/or anterior compartment pelvic organ prolapse underwent prolapse reduction to screen for stress urinary incontinence. Patients with clinical, occult and urodynamic stress urinary incontinence underwent a sling procedure. Those without stress urinary incontinence did not undergo sling surgery. Patients completed responses to the UDI-6 (Urogenital Distress Inventory, PGI-I (Patient Global Impression of Improvement) and MESA (Medical, Epidemiological, and Social Aspects of Aging). Cost analysis of selective urethral management was completed. RESULTS: A total of 42 patients met the study inclusion criteria and 30 completed responses to all questionnaires. Patients were separated into prolapse repair only (14) and prolapse repair with sling (16) groups. In the prolapse repair only group 1 patient required a subsequent sling. Mean UDI-6, MESA urge and MESA stress scores were 3.71, 1.29 and 3.14 in the prolapse repair only group, and 2.31 (p=0.219), 2.69 (p=0.244) and 3.00 (p=0.918) in the prolapse repair with sling group, respectively. The PGI-I revealed no statistical difference between the groups. A total cost savings of $55,804 was achieved using selective urethral management. CONCLUSIONS: Patients undergoing prolapse repair only have continence and satisfaction outcomes that appear equivalent to those who underwent concomitant prolapse repair and sling. The decision to perform a concomitant sling at the time of prolapse repair should be tailored to the patient.

Does estrogen have any real effect on voiding dysfunction in women?

For many years, estrogen has been used to treat lower urinary tract dysfunction in postmenopausal women. The data supporting this practice vary. Large multi-institutional studies have shown little role for systemic estrogens in the treatment of urinary incontinence. Vaginal estrogen preparations show superiority to systemic estrogens for the treatment of irritative voiding symptoms in meta-analysis, but there is significant study heterogeneity and the practice remains debatable. Data from randomized controlled trials support estrogen use in the prevention of recurrent urinary tract infections. This article reviews the relevant literature addressing the role of estrogen therapy in urinary incontinence, irritative voiding symptoms, and recurrent urinary tract infections.

Therapeutic effects of endothelin-A receptor antagonist on bladder overactivity in rats with chronic spinal cord injury.

OBJECTIVES: We investigated the effects of suppression of endothelin-A (ET(A)) receptors on bladder function and ET-1 levels in the bladder in rats with chronic spinal cord injury (SCI). METHODS: We transected the spinal cord of female Sprague-Dawley rats at the level of Th 8-9. Awake cystometrograms were performed 4 weeks after spinal cord transection. We evaluated cystometric parameters such as mean amplitudes of nonvoiding contractions (NVCs), the number of NVCs, voided volume, voiding efficiency, and micturition pressure before and after intravenous (i.v.) injection of ABT-627, an ET(A) antagonist, or A-19261, an ET(B) antagonist, in SCI animals. Four weeks after spinalization, we also measured the protein and mRNA levels of ET-1 in the bladder using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: ABT-627 (1 mg/kg, i.v.) but not A-192621 (10 mg/kg, i.v.) significantly decreased the amplitude of NVCs and the number of NVCs in SCI rats. There were no significant changes in pressure threshold, maximum voiding pressure, voided volume, or voiding efficiency. ELISA analysis for ET-1 showed significantly elevated protein concentrations in SCI rats compared with spinal cord intact rats. Significant upregulation of the ET-1 mRNA was also noted in SCI bladders. CONCLUSIONS: These results suggest that upregulation of ET-1 is involved in the mechanism inducing bladder overactivity in chronic SCI rats, and that an ET(A) receptor antagonist can suppress SCI-induced bladder overactivity as indicated by a reduction in NVCs. Thus, ET(A) receptor inhibition could be an effective treatment for neurogenic bladder overactivity in pathological conditions such as SCI.