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.

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.

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.

[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.

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.

Hunner lesion disease differs in diagnosis, treatment and outcome from bladder pain syndrome: an ESSIC working group report.

Objectives: There is confusion about the terms of bladder pain syndrome (BPS) and Interstitial Cystitis (IC). The European Society for the Study of IC (ESSIC) classified these according to objective findings [9]. One phenotype, Hunner lesion disease (HLD or ESSIC 3C) differs markedly from other presentations. Therefore, the question was raised as to whether this is a separate condition or BPS subtype.Methods: An evaluation was made to explore if HLD differs from other BPS presentations regarding symptomatology, physical examination findings, laboratory tests, endoscopy, histopathology, natural history, epidemiology, prognosis and treatment outcomes.Results: Cystoscopy is the method of choice to identify Hunner lesions, histopathology the method to confirm it. You cannot distinguish between main forms of BPS by means of symptoms, physical examination or laboratory tests. Epidemiologic data are incomplete. HLD seems relatively uncommon, although more frequent in older patients than non-HLD. No indication has been presented of BPS and HLD as a continuum of conditions, one developing into the other.Conclusions: A paradigm shift in the understanding of BPS/IC is urgent. A highly topical issue is to separate HLD and BPS: treatment results and prognoses differ substantially. Since historically, IC was tantamount to Hunner lesions and interstitial inflammation in the bladder wall, still, a valid definition, the term IC should preferably be reserved for HLD patients. BPS is a symptom syndrome without specific objective findings and should be used for other patients fulfilling the ESSIC definitions.

Does repeated hydrodistension with transurethral fulguration for interstitial cystitis with Hunner's lesion cause bladder contraction?

Objective: To evaluate the effect of repeated bladder hydrodistension with transurethral resection or fulguration (TUF) of Hunner's lesions on bladder capacity and interstitial cystitis (IC) symptoms. TUF for Hunner's lesion is recommended in several IC/BPS guidelines, although recurrence is highly probable. Patients and methods: The study cohort comprised 44 IC patients with Hunner's lesions who underwent multiple bladder hydrodistensions with TUF and electrocautery (EC) at our institution between July 2005 and June 2018. We analysed their frequency-volume chart, O'Leary Sant Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), and visual analogue scale (VAS) for pain, before and at 2, 6, and 12 months after surgery. Results: The 44 Hunner-type IC patients underwent a total of 117 surgeries. Patients were divided into three groups based upon the number of hydrodistensions with TUF they underwent. Group 1 (n = 44), Group 2 (n = 44) and Group 3 (n = 21) underwent one, two, and three surgeries, respectively. At 6 months after surgery, the mean average voided volume (AVV) and maximum voided volume (MVV) were 157 mL and 228 mL in Group 1; 203 mL, 283 mL in Group 2; and 193 mL, 264 mL in Group 3. The AVV in Group 2 (P < 0.01) and Group 3 (P < 0.03), and the MVV in Group 2 (P < 0.02) increased significantly compared to Group 1. ICSI, ICPI and VAS pain score in groups 2 (P < 0.003, P < 0.01, P < 0.05) and 3 (P < 0.001, P < 0.001, P < 0.001) decreased significantly compared to Group 1. Conclusion: Repeated hydrodistension and TUF with EC of Hunner's lesions for recurrent Hunner-type IC patients improved their symptoms. There was a tendency toward an increase in bladder capacity and repeated hydrodistension with TUF did not appear to be a direct cause of bladder contraction. Abbreviations: AVV: average voided volume; BPS: bladder pain syndrome; EC: electrical cautery; IC: interstitial cystitis; ICPI: Interstitial Cystitis Problem Index; ICSI: Interstitial Cystitis Symptom Index; MVV: maximum voided volume; TUF: transurethral fulguration; TUR: transurethral resection; VAS: visual analogue scale.

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.

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.

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.

Clinical Guideline for Female Lower Urinary Tract Symptoms.

The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery.