Nocturia in Menopausal Women: The Link Between Two Common Problems of the Middle Age.

INTRODUCTION AND HYPOTHESIS: The aim of this review is to discuss the link between menopause and nocturia and to give an overview of the increasing prevalence, risk factors, causative factors, treatment needs and options for nocturia in peri-menopausal women. METHODS: This opinion article is a narrative review based on the expertise and consensus of a variety of key opinion leaders, in combination with an extensive literature review. This literature search included a thorough analysis of potential publications on both the PubMed Database and the Web of Science and was conducted between November 2022 and December 2022. The following key words were used "nocturia" and "menopause" or "nocturnal frequency and menopause." Moreover, key words including "incidence," "prevalence," "insomnia," "estrogen therapy," "metabolic syndrome," and "hot flushes" were used in combination with the aforementioned key words. Last, the reference lists of articles obtained were screened for other relevant literature. RESULTS: The perimenopause can be a trigger for inducing nocturia. Typically, obesity, body mass index (BMI), and waist circumference are risk factors for developing peri-menopausal nocturia. Presumably the development of peri-menopausal nocturia is multifactorial, with interplay among bladder, sleep, and kidney problems due to estrogen depletion after the menopause. First, impaired stimulation of estrogen receptors in the urogenital region leads to vaginal atrophy and reduced bladder capacity. Moreover, menopause is associated with an increased incidence of overactive bladder syndrome. Second, estrogen deficiency can induce salt and water diuresis through blunted circadian rhythms for the secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone system. Additionally, an increased incidence of sleep disorders, including vasomotor symptoms and obstructive sleep apnea signs, is observed. Oral dryness and a consequent higher fluid intake are common peri-menopausal symptoms. Higher insulin resistance and a higher risk of cardiovascular diseases may provoke nocturia. Given the impact of nocturia on general health and quality of life, bothersome nocturia should be treated. Initially, behavioral therapy should be advised. If these modifications are inadequate, specific treatment should be proposed. Systemic hormone replacement is found to have a beneficial effect on nocturia, without influencing sodium and water clearance in patients with nocturnal polyuria. It is presumed that the improvement in nocturia from hormonal treatment is due to an improvement in sleep disorders.

Should hormone replacement therapy (any route of administration) be considered in all postmenopausal women with lower urinary tract symptoms? Report from the ICI-RS 2023.

AIMS: This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. METHODS: An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. RESULTS: There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended. CONCLUSIONS: Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing.

What is the best first choice oral drug therapy for OAB?

AIMS: The management of overactive bladder (OAB) involves lifestyle changes and conservative measures in the first instance with the use of liquid/dietary advice, weight loss, and bladder training. Thereafter oral pharmacotherapy is instigated in symptomatic patients. Antimuscarinics and beta 3 agonists form the main classes of drug therapy in this field. Views on what is the best first line OAB treatment is changing based on recent evidence and adverse event profiles of these medications. METHODS: At the ICI-RS meeting 2023, Bristol, UK this topic was discussed and debated as a proposal. The following article summarizes the concepts presented that day as well as the interactive discussion that took place thereafter. RESULTS: OAB guidelines are moving in many circumstances to an either antimuscarinic or beta 3 agonist approach based on patient factors. Several studies have raised concerns on the long-term impact of antimuscarinics, in relation to cognition, dementia, cardiovascular events, and mortality all related to antimuscarinic load. Neither antimuscarinics nor beta 3 agonists have good persistence and adherence rates in the medium to long term. Several barriers also exist to prescribing including guidelines recommending utilizing drugs with the lowest acquisition cost and "step therapy." A newer approach to managing OAB is personalized therapy in view of the many possible etiological factors and phenotypes. These concepts are highlighted in this article. CONCLUSIONS: Current oral pharmacotherapy in managing OAB is limited by adverse events, adherence and persistence problems. Both antimuscarinics and beta 3 agonists are efficacious but most clinical trials demonstrate significant placebo effects in this field. Personalizing treatment to the individual seems a logical approach to OAB. There is a need for better treatments and further studies are required of existing treatments with high quality longer term outcomes.

Treating and Managing Urinary Incontinence: Evolving and Potential Multicomponent Medical and Lifestyle Interventions.

Incontinence is defined by either ICS 2002 or IUGA/ICS 2010 as the involuntary loss of urine and includes urgency urinary incontinence (UUI), stress urinary incontinence (SUI) or mixed urinary incontinence (MUI). It has a high worldwide prevalence with an associated impact on quality of life. Despite existing management options for the management of urinary incontinence, patients continue to be troubled by symptoms or side effects of existing treatment. There is therefore a requirement for ongoing research into treatment options for the management of UUI and SUI, that are more effective and tolerable to patients. Advances in treatment of UUI include a more selective beta 3 agonist, Vibegron, which has less impact on cardiac function than Mirabegron. Hormonal treatment, including Ospemifene and Prasterone, may improve GSM and in turn symptoms of UUI. There are advances in the types of neuromodulators available, including those that are rechargeable at home and are MRI safe. Laser has shown promising initial results. There is developing interest in the microbiome, and how this may impact future treatment modalities. Advances in treatment of SUI include the use of mobile health applications to support delivery of pelvic floor muscle training. Litoxetine, a selective serotonin reuptake inhibitor, has shown promising results at phase III trials. Functional magnetic stimulation is being developed to improve contractility of pelvic floor muscles. We also discuss interventions that improve tissue elasticity and regeneration, such as platelet rich plasma, autologous stem cell transplantation, laser therapy and radiofrequency treatment, which show short term benefits.

Adherence to Overactive Bladder Syndrome Treatments Recent Developments and Future Perspectives.

Overactive bladder (OAB) is a common and distressing condition which is known to have a significant effect on Health-Related Quality of Life (HRQoL). Whilst all patients complaining of overactive bladder symptoms will, in theory, initially benefit from conservative measures, many will require pharmacological therapy. Antimuscarinics currently remain the most commonly used drugs to treat OAB although compliance and persistence can be poor due to concerns regarding adverse events and lack of efficacy. This review will explore the common management strategies for OAB with a particular focus on patient adherence to therapy including compliance and persistence. The role of antimuscarinics and the B3-agonist, mirabegron, will be considered along with barriers to their efficacy and adoption. For those patients in whom conservative and pharmacological treatment proves ineffective or is unsuitable, the management of refractory OAB will also be considered. In addition, the role of current and future developments will be examined.

Mixed urinary incontinence: Are there effective treatments?

The aim of this debate article is to discuss whether effective treatments are available for mixed urinary incontinence (MUI). Because patients with MUI have both stress and urgency urinary incontinence (SUI and UUI) episodes and current treatment guidelines currently recommend treating the predominant symptom first, this article presents standard and emerging treatments for both SUI and UUI before discussing how well these treatments meet the medical needs of patients with MUI. Standard treatments presented include noninvasive options such as lifestyle changes and pelvic floor exercises, pharmacological agents, and surgery. Treatment of all three types of urinary incontinence (UI) is usually initiated with noninvasive options, after which treatment options diverge based on UI subtype. Multiple pharmacological agents have been developed for the treatment of UUI and overactive bladder, whereas surgery remains the standard option for SUI and stress-predominant MUI. The divide between UUI and SUI options seems to be propagated in emerging treatments, with most novel pharmacological agents still targeting UUI and even having SUI and stress-predominant MUI as exclusion criteria for participation in clinical trials. Considering that current treatment options focus almost exclusively on treating the predominant symptom of MUI and that emerging pharmacological treatments exclude patients with stress-predominant MUI during the development phase, effective treatments for MUI are lacking both in standard and emerging practice. Ideally, agents with dual mechanisms of action could provide symptom benefit for both the stress and urgency components of MUI.

Mirabegron in the Management of Overactive Bladder Syndrome.

Overactive bladder (OAB) negatively affects work productivity and quality of life in sufferers. Its overall impact is likely to increase as a result of increasing prevalence in an ageing population. The pathophysiology of OAB is not completely understood but the ß3-adrenoceptor, which is highly expressed in the urinary bladder, is thought to be important for mediating human detrusor relaxation during the storage phase. Clinical trial results have demonstrated that mirabegron, a selective ß3-adrenoceptor agonist offers substantial clinical efficacy and good adherence rates over 12 months. Furthermore, due to its different mechanism of action, it is likely to offer a favourable tolerability profile when compared with antimuscarinic agents, resulting in improved persistence over long-term treatment. Finally, from a health economic perspective, despite its higher drug acquisition cost, mirabegron has been found to be cost-effective, owing to the greater increase in quality-adjusted-life-years gained, when compared to antimuscarinic medications. The PubMed database was searched for English language articles published between 1 January 2005 to 31 January 2022, on the subject of mirabegron. Search terms included "mirabegron", "overactive bladder", "ß3-adrenoceptor agonist", "urinary incontinence". This review summarises the evidence for mirabegron as a treatment option for the management of OAB.

International Urogynaecology Consultation chapter 1 committee 4: patients' perception of disease burden of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: This manuscript from Chapter 1 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) reports on the patients' perception of disease burden associated with pelvic organ prolapse. MATERIALS AND METHODS: An international group containing a team of eight urogynaecologists, a physiotherapist and a statistician performed a search of the literature using pre-specified search terms in PubMed and Embase (January 2000 to August 2020). The division of sections within this report includes: (1) perception of POP and the relationship with body image and poor health; (2) a vaginal bulge as it impacts health and wellbeing in women; (3) the impact of POP on sexual life; (4) body image and pelvic floor disorders; (5) POP and mood; (6) appropriate use of treatment goals to better meet patients' expected benefits; (7) using health-related quality of life questionnaires to quantify patients' perception of POP; (8) The financial burden of POP to patients and society. Abstracts were reviewed and publications were eliminated if not relevant or did not include populations with POP or were not relevant to the subject areas as noted by the authors. The manuscripts were next reviewed for suitability using the Specialist Unit for Review Evidence (SURE) checklists for cohort, cross-sectional and case-control epidemiologic studies. RESULTS: The original individual literature searches yielded 2312 references of which 190 were used in the final manuscript. The following perceptions were identified: (1) women were found to have varying perceptions of POP including shame and embarrassment. Some regard POP as consequence of aging and consider there is no effective therapy. (2) POP is perceived as a vaginal bulge and affects lifestyle and emotional wellbeing. The main driver for treatment is absence of bulge sensation. (3) POP is known to affect frequency of sexual intercourse but has less impact on satisfaction. (4) Prolapse-specific body image and genital self-image are important components of a women's emotional, physical and sexual wellbeing. (5) POP is commonly associated with depression and anxiety symptoms which impact HRQoL although are not correlated with objective anatomical findings. (6) Patient-centered treatment goals are useful in facilitating communication, shared decision-making and expectations before and after reconstructive surgery. (7) Disease-specific HRQoL questionnaires are important tools to assess bother and outcome following surgery, and there are now several tools with Level 1 evidence and a Grade A recommendation. (8) The cost of POP to the individual and to society is considerable in terms of productivity. In general, conservative measures tend to be more cost-effective than surgical intervention. CONCLUSIONS: Patients' perception of POP varies in different patients and has a far-reaching impact on their overall state of health and wellbeing. However, recognizing that it is a combination of body image and overall health (which affects mental health) allows clinicians to better tailor expectations for treatment to individual patients. There are HRQoL tools that can be used to quantify these impacts in clinical care and research. The costs to the individual patient (which affects their perception of POP) is an area that is poorly understood and needs more research.

A randomized, placebo-controlled clinical development program exploring the use of litoxetine for treating urinary incontinence.

AIMS: To investigate the safety and efficacy of litoxetine, a serotonin reuptake inhibitor, in treating urinary incontinence (UI) and mixed urinary incontinence (MUI). METHODS: Two randomized, double-blind, placebo-controlled clinical trials (RCT1 and RCT2) were conducted. RCT1, which included 196 women aged 18-75 with MUI randomized 1:1:1:1 to receive 10, 20, or 40 mg litoxetine or placebo orally twice daily (BID) for 12 weeks, investigated the efficacy (including changes in patient reported outcomes) and safety of litoxetine compared to placebo. RCT2, which included 82 men and women aged 18-70 with any UI type randomly assigned 2:1 to receive 30 mg litoxetine or placebo orally BID for 8 weeks including a 2 week dose titration period, investigated the safety (including psychiatric safety) and efficacy of litoxetine compared to placebo. Efficacy was measured as the change in number of incontinence episodes per week and assessed using an analysis of covariance with missing data imputed by Predictive Mean Matching. Safety was assessed by adverse events (AEs) and physical examinations and analyzed using descriptive statistics. RESULTS: The 30-mg and placebo groups in RCT2 showed no difference in frequency of AEs, and litoxetine reduced the number of incontinence episodes per week compared to placebo. Although RCT1 suffered an unexpectedly high placebo response, and therefore did not meet the primary efficacy endpoint, 71% of participants receiving 40 mg litoxetine reported a clinically meaningful improvement in the King's Health Questionnaire. CONCLUSIONS: Litoxetine may be a safe, effective and well-tolerated treatment for patients with UI.

Healthcare professional's choice for surgical management of stress urinary incontinence in a U.K. tertiary hospital.

OBJECTIVE: In July 2018, NHS England, introduced a pause on vaginal mesh, including the mid-urethral sling (MUS) for treatment of stress urinary incontinence (SUI). NICE guidelines recommend MUS as one of the surgical options for SUI. The aim of our study was to investigate healthcare professionals choices for surgical treatment of SUI, if conservative measures failed. STUDY DESIGN: The urogynaecology department at our tertiary level hospital devised a questionnaire using SurveyMonkey. This was distributed via email to 1058 healthcare professionals of different medical backgrounds. The surgical options were based on the NICE guideline and its patient decision making aid. We also used surgical information from the British society of Urogynaecology (BSUG) and British association of urological surgeons (BAUS). RESULTS: We received 214 responses of which 204 were complete. Twenty six percent of replies were from obstetricians and gynaecologists, 36 % had over 20 years experience and 79 % were female. Forty four percent had no previous knowledge of surgical options. Mid-urethral sling was the most popular choice based on description, success and specific complications. Urethral bulking agent was the only option that increased in popularity after describing complications. Twenty two percent would avoid surgery due to the risk of complications. CONCLUSION: This is the first study evaluating healthcare professionals surgical choice for SUI. Despite negative media publicity and NHS pause on MUS, it was still the most popular choice before and after informing of specific complications. The urethral bulking agent was the only surgical treatment, which increased in popularity after considering complications.

Modern management of genitourinary syndrome of menopause.

The genitourinary syndrome of menopause (GSM) is the accepted term used to describe the broad spectrum of genitourinary tract symptoms and signs caused by the loss of endogenous sex steroids that occurs at the time of and after the menopause. Global improvements in healthcare have resulted in an ageing population. Today, women are spending 40% of their lives in the postmenopausal state, and with 50-70% of postmenopausal women reporting symptomatic GSM, safe and efficacious treatments are needed for this troublesome condition. This article reviews current evidence for non-pharmacological and pharmacological treatments with a focus on novel and minimally invasive procedures such as energy-based devices (CO2 laser, YAG laser), hyaluronic acid, dehydroepiandrosterone, and selective oestrogen receptor modulators.

Pharmacist's knowledge regarding the management of overactive bladder in elderly women.

OBJECTIVE: Anticholinergic drugs are the mainstay treatment of OAB. Anticholinergic load is the cumulative effect of taking anticholinergic medication. Recent evidence suggests that in the elderly this can have a detrimental affect, with the potential to develop dementia. A previous study found that knowledge of anticholinergic load was lacking in our healthcare professionals. The aim of this study was to assess knowledge of pharmacists, who in the UK have the potential where qualified to prescribe as well as dispense. STUDY DESIGN: A questionnaire was formulated based on the previous study. It was sent out to 418 pharmacists from; a south London hospital trust, a south London clinical commissioning group and United Kingdom Clinical Pharmacists Association. RESULTS: Seventy-five pharmacists completed the questionnaire. Solifenacin and tolterodine was the most popular drug prescribed in the elderly without dementia, whilst mirabegron was the most popular in the elderly with dementia. One pharmacist suggested using oxybutynin. Sixty-two percent discuss anticholinergic load with the patients, 40 % advice prescribers and 42 % consider anticholinergic load when dispensing the drug. Fifteen percent have had patients report confusion/memory loss. Thirty percent know how to assess anticholinergic load. Only 15 % felt dementia was a concern with anticholinergic drugs. Worryingly, 54 % though mirabegron exerted anticholinergic effects. CONCLUSION: This is the first study looking at pharmacist knowledge on the use of anticholinergic medication for OAB in elderly women. Knowledge amongst all healthcare professionals including pharmacists is lacking and needs to be improved.

The use of 3D ultrasound in comparing surgical techniques for posterior wall prolapse repair: a pilot randomised controlled trial.

The most appropriate method for repairing posterior vaginal wall prolapse is still debatable. Women with symptomatic prolapse scheduled to undergo surgical repair in the posterior compartment were randomised to standard posterior colporrhaphy (SPC) or fascial and vaginal epithelial plication (FEP). Participants were assessed with the Prolapse Quality of Life (P-QOL) questionnaire, pelvic organ prolapse quantification (POP-Q) examination and three-dimensional ultrasound (3D US) prior to surgery and 6 months postoperatively. The research hypothesis is that 3D US of the pelvic floor is a reliable tool in comparing the anatomical outcomes of the two different surgical techniques. Differences in anatomical outcomes, assessed clinically and by ultrasonographic evaluation, were compared between the two groups using the Independent Mann-Whitney U-test and the Wilcoxon signed-rank sum test. Twenty-two women were included in the analysis. Six months postoperatively, women in the FEP arm had better anatomical outcomes compared to those who had undergone SPC (p = .02). Repeatability of the ultrasound technique was confirmed, showing moderate to very good agreement in all parameters and the 3D US evaluation was corroborated with the clinical examination, showing a greater reduction in the urogenital size in the FEP group.Impact statementWhat is already known on this subject? The low cost and universal availability of the ultrasound (US) makes it the most commonly used diagnostic modality. The ability to see beyond surface anatomy is important and useful in the assessment of the posterior vaginal wall prolapse and the obstructed defaecation, where this method may replace the defaecation proctography (Dietz 2019). Recent advances in pelvic floor ultrasonography (3D US) have achieved repeatability in the measurement of the levator hiatal (LH) dimensions, introducing a valid and readily available tool for researchers and clinicians (Dietz et al. 2005). Ultrasound may distinguish a true rectocele due to the weakening of the rectovaginal fascia from an enterocele, a rectal intussusception, or just a deficient perineum (Guzman Rojas et al. 2016).What do the results of this study add? Our study demonstrates that 3D translabial pelvic floor ultrasound is a useful and reliable tool in assessing the anatomical outcome of prolapse surgery.What are the implications of these findings for clinical practice and/or further research? Our study demonstrates that 3D translabial ultrasound of the pelvic floor is a useful and reproducible method in evaluating the anatomical outcomes of surgical repair for posterior wall prolapse. Genital hiatus (GH) and levator hiatus (LH) dimensions measured by ultrasound can be used as surrogate anatomical markers in comparing the efficacy of different surgical techniques.

Defining nocturnal polyuria in women.

AIMS: Nocturnal polyuria (NP) is defined by the International Continence Society (ICS) as "excessive production of urine during the main sleep period" and is one of the main causes of nocturia. The ICS recognized that "excessive" is not clearly defined and that this needs to be highlighted in both clinical and research settings. The aim of this study was to identify different definitions of NP and apply them to a population of women attending the Urogynaecology clinic. METHODS: This was a retrospective study of complete bladder diaries collected from women attending a tertiary Urogynaecology Unit. Six different definitions were identified and were divided into "absolute," "relative," and "functional definitions." Prevalence data were calculated and values generated for sensitivity, specificity, positive and negative predictive values when related to women voiding ≥ 2 times per night. RESULTS: Complete bladder diaries were obtained from 1398 women, over 6 years, with a mean age of 57 years. Prevalence varied across the definitions from 21.5% (absolute definition) to 77% (relative definition). Sensitivity ranged from 43% (absolute) to 87% (relative). The definitions that showed the highest combined sensitivity and specificity were the functional definitions. CONCLUSION: From this study it is clear that more work needs to be done to arrive at a consensus for defining NP to enable accurate diagnosis and development of treatment pathways. We propose that a relative definition may provide a more clinically relevant method of defining NP.