Female sexual dysfunction and lower urinary tract symptoms associated with vulvovaginal atrophy symptoms: Results of the GENJA study.

OBJECTIVES: To investigate the main symptoms of female sexual dysfunction (FSD) and lower urinary tract symptoms associated with vulvovaginal atrophy (VVA) symptoms as the core symptoms of genitourinary syndrome of menopause. METHODS: We extracted the data of 4134 Japanese women aged 40-79 years who participated in the GENitourinary syndrome of menopause in JApanese women (GENJA) study. All participants responded to web-based questionnaires assessing their health situation, including the Vulvovaginal Symptoms Questionnaire, the Female Sexual Function Index (FSFI), and the Core Lower Urinary Tract Symptom Score. Multivariable regression and multivariable logistic regression analyses were applied to analyze the association between VVA symptoms and FSD, and between VVA symptoms and lower urinary tract symptoms. RESULTS: Multivariable regression analysis revealed that VVA symptoms were associated with lower scores for arousal, lubrication, orgasm, satisfaction, and pain domains in the FSFI in sexually active women (p < 0.01). Regression coefficients were higher for lubrication and pain domains than for the other domains. Multivariable logistic regression analysis revealed that women reporting VVA symptoms were more likely to have increased daytime urinary frequency, nocturia, urgency, slow stream, straining to void, feeling of incomplete emptying, bladder pain, and feeling a bulge/lump from or in the vagina (p < 0.05). Adjusted odds ratios were particularly high for straining to void, feeling of incomplete emptying, and bladder pain. CONCLUSIONS: Vulvovaginal atrophy symptoms were significantly associated with decreased lubrication and dyspareunia in FSD, and urinary symptoms of straining to void, feeling of incomplete emptying, and bladder pain.

Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition).

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post-micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is <100 mL, then diagnosis and treatment for storage symptoms is prioritized, and if the volume is ≥100 mL, then specialized treatment should be considered. When storage symptoms are the primary condition, then the patient is subject to the primary treatment algorithm. Specialized treatment for refractory overactive bladder includes botulinum toxin injection and sacral nerve stimulation. For stress urinary incontinence, surgical treatment is indicated, such as urethral slings. The two causes of voiding symptoms and post-micturition symptoms are lower urinary tract obstruction and detrusor underactivity (underactive bladder). Mechanical lower urinary tract obstruction, such as pelvic organ prolapse, is expected to improve with surgery.

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

OBJECTIVE: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. METHODS: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. RESULTS: For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. CONCLUSIONS: This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

Clinical guidelines for interstitial cystitis/bladder pain syndrome.

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.

Surgery for urinary incontinence in women: Report from the 6th international consultation on incontinence.

Urinary incontinence is a prevalent condition worldwide and causes a tremendous impact on a woman's quality of life. While conservative and non-surgical therapies are options for treatment, surgery for stress urinary incontinence (SUI) is common. Options include colposuspension, slings (pubovaginal and midurethral), and periurethral bulking. While evidence supports each of these options in the treatment of SUI, each is associated with various rates of success and unique adverse event profiles. Urgency urinary incontinence (UUI) is initially treated with behavioral modification and pharmacologic means, with surgery reserved for those with refractory symptoms or significant complications from medication use. At present, intravesical onabotulinumtoxinA injections, percutaneous tibial nerve stimulation, and sacral neurostimulation are all viable options for refractory UUI/overactive bladder. As with surgical interventions for SUI, each of these is, likewise, associated with unique outcomes and adverse event profiles. Herein, we summarize the findings and conclusions from the 6th International Consultation on Incontinence (ICI) regarding surgical treatment of urinary incontinence in women.

Hunner lesion versus non-Hunner lesion interstitial cystitis/bladder pain syndrome.

BACKGROUND: Global consensus on the standardization of terminology for interstitial cystitis/bladder pain syndrome is lacking and is in the formative stages. The Workshop on Hunner lesion versus non-Hunner lesion at the 2018 International Consultation on Interstitial Cystitis Japan discussed prevalence, performance and outcome of endoscopy, the role of histopathology, and markers. METHODS: A panel of experts reviewed the literature regarding Hunner lesion vs. non-Hunner lesion interstitial cystitis/bladder pain syndrome. RESULTS: The prevalence of Hunner lesion has been reported to be 5-57%. Older age and smaller anatomic bladder capacity were associated with Hunner lesions. Cystoscopy using local anesthesia is not adequate in diagnosing interstitial cystitis but is needed to rule out confusable diseases. Cystoscopy with hydrodistention and redistention of the bladder is considered standard. A Hunner lesion is visualized as a quite typical inflammatory reaction: a reddened mucosal area with small vessels radiating towards a central scar, splitting at distension, usually associated with a waterfall bleeding pattern. Biopsies from the inflamed area show inflammatory infiltrates, granulation tissue, detrusor mastocytosis, and fibrin deposits. Ablation of Hunner lesions includes transurethral resection of lesions, fulguration, laser ablation, and cortical steroid injections. Mast cell density is a somewhat controversial matter, described differently in different studies: marked increase in Hunner lesion vs. non-Hunner lesion in the majority of studies, no difference in a few. Nitric oxide appears to be a definitive marker in distinguishing Hunner lesion vs. non-Hunner lesion disease. Macrophage migration inhibitory factor is elevated in Hunner lesion patients. Increased level of urinary proinflammatory genes expression has also been found in Hunner lesion subjects. CONCLUSIONS: Hunner lesion patients are clinically and pathologically distinct from non-Hunner lesion bladder pain syndrome patients.

What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017.

INTRODUCTION: Storage phase bladder activity is a counter-intuitive observation of spontaneous contractions. They are potentially an intrinsic feature of the smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as well as other muscular elements in the mucosa may substantially influence them. They are identified in several models explaining lower urinary tract dysfunction. METHODS: A consensus meeting at the International Consultation on Incontinence Research Society (ICI-RS) 2017 congress considered the origins and relevance of spontaneous bladder contractions by debating which cell type(s) modulate bladder spontaneous activity, whether the methodologies are sufficiently robust, and implications for healthy and abnormal lower urinary tract function. RESULTS: The identified research priorities reflect a wide range of unknown aspects. Cellular contributions to spontaneous contractions in detrusor smooth muscle are still uncertain. Accordingly, insight into the cellular physiology of the bladder wall, particularly smooth muscle cells, interstitial cells, and urothelium, remains important. Upstream influences, such as innervation, endocrine, and paracrine factors, are particularly important. The cellular interactions represent the key understanding to derive the integrative physiology of organ function, notably the nature of signalling between mucosa and detrusor layers. Indeed, it is still not clear to what extent spontaneous contractions generated in isolated preparations mirror their normal and pathological counterparts in the intact bladder. Improved models of how spontaneous contractions influence pressure generation and sensory nerve function are also needed. CONCLUSIONS: Deriving approaches to robust evaluation of spontaneous contractions and their influences for experimental and clinical use could yield considerable progress in functional urology.

A standard for terminology in chronic pelvic pain syndromes: A report from the chronic pelvic pain working group of the international continence society.

AIMS: Terms used in the field of chronic pelvic pain (CPP) are poorly defined and often confusing. An International Continence Society (ICS) Standard for Terminology in chronic pelvic pain syndromes (CPPS) has been developed with the aim of improving diagnosis and treatment of patients affected by chronic pelvic pain syndromes. The standard aims to facilitate research, enhance therapy development and support healthcare delivery, for healthcare providers, and patients. This document looks at the whole person and all the domains (organ systems) in a systematic way. METHODS: A dedicated working group (WG) was instituted by the ICS Standardisation Steering Committee according to published procedures. The WG extracted information from existing relevant guidelines, consensus documents, and scientific publications. Medline and other databases were searched in relation to each chronic pelvic pain domain from 1980 to 2014. Existing ICS Standards for terminology were utilized where appropriate to ensure transparency, accessibility, flexibility, and evolution. Consensus was based on majority agreement. RESULTS: The multidisciplinary CPPS Standard reports updated consensus terminology in nine domains; lower urinary tract, female genital, male genital, gastrointestinal, musculoskeletal, neurological aspects, psychological aspects, sexual aspects, and comorbidities. Each is described in terms of symptoms, signs and further evaluation. CONCLUSION: The document presents preferred terms and definitions for symptoms, signs, and evaluation (diagnostic work-up) of female and male patients with chronic pelvic pain syndromes, serving as a platform for ongoing development in this field. Neurourol. Urodynam. 36:984-1008, 2017. © 2016 Wiley Periodicals, Inc.

Prospective analyses of female urinary incontinence symptoms following total hip arthroplasty.

INTRODUCTION AND HYPOTHESIS: Some patients with hip osteoarthritis report that urinary incontinence (UI) is improved following total hip arthroplasty (THA). However, the type and severity of UI remain unclear. In this study, we hypothesize that both stress urinary incontinence (SUI) and urge urinary incontinence (UUI) are improved after THA. We assess the characteristics of UI and discuss the anatomical factors related to UI and THA for improved treatment outcome. METHODS: Fifty patients with UI who underwent direct anterior-approach THA were evaluated. Type of UI was assessed using four questionnaires: Core Lower Urinary Tract Symptom Score (CLSS), Urogenital Distress Inventory Short Form (UDI-6), International Prostate Symptom Score (IPSS), and Overactive Bladder Symptom Score (OABSS). Uroflowmetry and postvoid residual urine were measured using ultrasound technology. Hip-joint function was evaluated using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and range of motion (ROM). RESULTS: Of the 50 patients, 21 had SUI, 16 had mixed urinary incontinence (MUI), and eight had urgency urinary incontinence (UUI). In total, 36 patients were better than improved (72 %). The rate of cured and improved was 76 % for SUI, 100 % MUI, and 50 % UUI. The improvement of ROM was more significant in cured or improved patients than in stable or worse patients. CONCLUSIONS: Improvement in mild UI may be an added benefit for those undergoing THA for hip-joint disorders. These data suggest that for patients with hip-joint disorder, hip-joint treatment could prove to also be a useful treatment for UI.

Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015.

Clinical guidelines for interstitial cystitis and hypersensitive bladder have been updated as of 2015. The guidelines define interstitial cystitis by the presence of hypersensitive bladder symptoms (discomfort, pressure or pain in the bladder usually associated with urinary frequency and nocturia) and bladder pathology, after excluding other diseases explaining symptoms. Interstitial cystitis is further classified by bladder pathology; either Hunner type interstitial cystitis with Hunner lesions or non-Hunner type interstitial cystitis with mucosal bleeding after distension in the absence of Hunner lesions. Hypersensitive bladder refers to a condition, where hypersensitive bladder symptoms are present, but bladder pathology or other explainable diseases are unproven. Interstitial cystitis and hypersensitive bladder severely affect patients' quality of life as a result of disabling symptoms and/or comorbidities. Reported prevalence suggestive of these disorders varies greatly from 0.01% to >6%. Pathophysiology would be an interaction of multiple factors including urothelial dysfunction, inflammation, neural hyperactivity, exogenous substances and extrabladder disorders. Definite diagnosis of interstitial cystitis and hypersensitive bladder requires cystoscopy with or without hydrodistension. Most of the therapeutic options lack a high level of evidence, leaving a few as recommended therapeutic options.

Interstitial cystitis associated with primary Sjögren's syndrome successfully treated with a combination of tacrolimus and corticosteroid: A case report and literature review.

We report a case of interstitial cystitis (IC) associated with primary Sjögren's syndrome (SS) successfully controlled with combination therapy of tacrolimus and a corticosteroid. In 2011, a 69-year-old female, who had been diagnosed with primary SS 23 years ago, developed IC and was successfully treated with tacrolimus and prednisolone combination therapy. The mechanism of IC, including the involved autoimmunity, has not been elucidated. Clinical observation studies suggest a potential association between SS and IC. However, IC is currently thought to be underdiagnosed in patients with SS as well as in the general population. Based on our case and others reported previously, IC associated with SS responds well to immunosuppressive therapy. In particular, a combination of a calcineurin inhibitor (tacrolimus or cyclosporine) with a corticosteroid seems to be highly effective. The possibility of IC in patients with SS complaining of lower urinary tract symptoms without features of infection or other identifiable causes should be given attention.

Improvement of overactive bladder symptoms after tension-free vaginal mesh operation in women with pelvic organ prolapse: Correlation with preoperative urodynamic findings.

OBJECTIVES: To further elucidate the mechanisms of overactive bladder coexisting with pelvic organ prolapse. METHODS: A total of 100 consecutive women with stage 2 or greater pelvic organ prolapse associated with cystocele were enrolled in the present prospective study. They underwent urodynamic studies and then received tension-free vaginal mesh operation. Urodynamic studies were carried out before and after the correction of pelvic organ prolapse using a single gauze pack in the vagina in the sitting position. The overactive bladder symptom score and International Prostate Symptom Score were collected before and 3 months after surgery. RESULTS: In 53 of 100 cases, pelvic organ prolapse was accompanied with overactive bladder, and detrusor overactivity was observed in 28 out of 53 pelvic organ prolapse with overactive bladder cases (52.8%). Detrusor overactivity was resolved in 18 and reduced in four out of 28 cases after the correction of pelvic organ prolapse by the gauze packing method. Of 53 patients who had overactive bladder preoperatively, overactive bladder symptoms disappeared in 35 cases (66.0%) and improved in six additional cases (11.3%) after tension-free vaginal mesh operation. A total of 20 of 25 cases whose overactive bladder symptoms disappeared or improved after surgery coincided with those who had shown either disappearance (n = 16) or improvement (n = 4) of detrusor overactivity after intravaginal gauze pack insertion in preoperative urodynamic studies. All scores in the overactive bladder symptom score decreased significantly after tension-free vaginal mesh, as well as the International Prostate Symptom Score, except for night-time frequency. CONCLUSIONS: Pelvic organ prolapse-associated overactive bladder or detrusor overactivity conditions can be reversed in most cases within a short period of time after surgical correction of pelvic organ prolapse.

[Linguistic validation of Japanese version of Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)].

PURPOSE: To translate the Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) into Japanese and evaluate the linguistic validation of the translated PISQ-IR. METHODS: The translation and evaluation of PISQ-IR were performed through 3 steps: forward translation based on 2 urologists and discussed by another 4 urologists, 1 pharmacoeconomist and 1 nurse; the community review process consists of conducting one-on-one cognitive interviews with 20 patients by a professional interviewer; backward translation by a native English speaker, which was negotiated with the PISQ-IR Working Group comprised original authors in International Urogynecological Association (IUGA). RESULTS: The PISQ-IR Working Group generally approved our translation and had 2 major concerns in the Japanese version; 1) "disagree" in every sentence of English version was not translated into Japanese, and 2) the Japanese expression in "sexual desire" should be more emotional. The former concern was approved by explaining that Japanese does not have the word which is the equivalent of "disagree", and "don't agree" is always used instead of "disagree". The latter concern was compromised by switching to a translation using emotional words. CONCLUSION: The Japanese version of PISQ-IR was translated in a linguistically valid manner. It would be equivalent to the original English questionnaire. It may provide a tool to assess sexual function for Japanese women with prolapse, urinary incontinence and/or fecal incontinence in an internationally harmonized fashion.

Epidemiological study of genitourinary syndrome of menopause in Japan (GENJA study).

OBJECTIVE: This study aimed to investigate the prevalence of genitourinary syndrome of menopause (GSM) in Japan using the Japanese translation of the Vulvovaginal Symptoms Questionnaire (VSQ) with online survey. In addition, we examined the relationship between sexual activity and GSM symptoms. METHODS: An online survey on GSM was conducted with 4,134 women aged 40 to 79 years, who were registered in an online survey company. Several questionnaires with Japanese translations of linguistic validity were used in this study. GSM was defined as a condition in women older than 40 years with vulvovaginal symptoms on the VSQ. RESULTS: The percentage of postmenopausal women 40 years and older was 69.6%. The percentage of women with sexual activity was 22%. The prevalence of GSM with vulvovaginal symptoms was 11.6%, and 31.7% in sexually active women. The prevalence of GSM was associated with age and was significantly lower in the 70s age group than in other age groups. Vulvar hurting and dryness were both age-related only in the sexual activity group, with a statistically significantly higher prevalence in the 70s group than in the 40s group. The prevalence of vulvar dryness during sexual activity was significantly lower in the 40s age group. CONCLUSIONS: An online epidemiological survey of GSM was conducted for the first time in Japan using the linguistically validated Japanese translation of the VSQ. The prevalence of GSM with genital or sexual symptoms was 11.6% in Japanese women 40 years and older, and 31.7% in sexually active women.

[LINGUISTIC VALIDATION OF JAPANESE VERSION OF THE VULVOVAGINAL SYMPTOMS QUESTIONNAIRE (VSQ)].

(Purpose) To translate the Vulvovaginal Symptoms Questionnaire (VSQ) into Japanese and evaluate the linguistic validation of the translated VSQ. (Methods) The translation and evaluation of the VSQ were performed through 3 steps: forward translation based on 2 urologists and discussed by another 3 urologists; the community review process, which consisted of one-on-one cognitive interviews with 20 patients by professional interviewers; backward translation by a native English speaker, which was discussed with the original author of the VSQ. (Results) The original author of the VSQ generally approved our translation. (Conclusion) The Japanese version of the VSQ was translated in a linguistically valid manner. It is equivalent to the original English questionnaire. It may provide a tool to assess sexual function for Japanese women with genitourinary syndrome of menopause.

Surgical treatment of female stress urinary incontinence with a transobturator tape (Monarc): short-term results of a prospective multicenter study.

AIM: Transobturator tape (TOT) kits approved as medical instruments are still not available in Japan. This study aimed to: (1) assess the outcomes of TOT using Monarc (American Medical Systems; AMS Inc, Minnetonka, MN, USA) in women with stress urinary incontinence (SUI); (2) evaluate possible different surgical outcomes in women with urethral hypermobility (UH) and/or intrinsic urethral deficiency (ISD); and (3) evaluate the possibility of improvement of preoperative urgency and urge urinary incontinence after TOT in mixed urinary incontinence (MUI). METHODS: Data from 140 women with SUI in a prospective multicenter study were examined at 3-6 months follow-up. RESULTS: 82.1% of the patients were cured and 10.7% showed improvement. The surgical outcome was significantly better in UH than in UH combined with ISD or ISD. In 44 MUI patients, 79.6% were cured and 15.9% showed improvement. Urgency improved in about 75% of patients after TOT. CONCLUSION: TOT is effective for both SUI and MUI, with urgency improving.