Weight loss with bariatric surgery or behaviour modification and the impact on female obesity‐related urine incontinence: A comprehensive systematic review and meta‐analysis

Women with obesity are at risk of pelvic floor dysfunction with a 3‐fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). The National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) recommend that women with a body mass index ≥30 kg/m2 should consider weight loss prior to consideration for incontinence surgery. This systematic review and meta‐analysis will assess this recommendation to aid in the counselling of women with obesity‐related urinary incontinence (UI). Medical Literature Analysis and Retrieval System online (MEDLINE), EMBASE, Cochrane, ClinicalTrials.gov, and SCOPUS were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori and presented original, empirical data relevant to weight loss intervention in the management of urinary incontinence. Thirty‐three studies and their outcomes were meta‐analysed. Weight loss interventions were associated in a decreased prevalence in UI (OR 0.222, 95% CI [0.147, 0.336]), SUI (OR 0.354, 95% CI [0.256, 0.489]), UUI (OR 0.437, 95% CI [0.295, 0.649]) and improved quality of life (PFDI‐20, SMD ‐0.774 (95% CI [−1.236, −0.312]). This systematic review and meta‐analysis provide evidence that weight loss interventions are effective in reducing the prevalence of obesity‐related UI symptoms in women. Bariatric surgery in particular shows greater sustained weight loss and improvements in UI prevalence. Further large scale, randomized control trials assessing the effect of bariatric surgery on women with obesity‐related UI are needed to confirm this study's findings.


| INTRODUCTION
Obesity is a growing pandemic, with the World Health Organization (WHO) reporting that obesity has nearly tripled worldwide since 1975. 1 In 2016, more than 1.9 billion adults were overweight (body mass index [BMI] ≥25 kg/m 2 ), and of these, over 650 million were obese (BMI ≥30 kg/m 2 ). Obesity is associated with an increased prevalence in multiple non-communicable diseases. 1 Urinary incontinence (UI) is defined as the involuntary loss of urine 2 and is a common health condition that can significantly affect an individual's quality of life (QoL). 3 Reportedly, approximately 50% of adult women may experience UI, 4 double the prevalence of UI documented in men. 5 This difference in prevalence is due to the structure of the female urinary tract, as well as risk factors such as pregnancy, childbirth, and hysterectomy that can damage the pelvic floor musculature and connective tissue. 5 Obesity is an independent risk factor for urinary storage (leakage) and UI symptoms 6 ; such that a 5 points increase of BMI is associated with a 20%-70% increased risk of UI. 6 Urge urinary incontinence (UUI) is the involuntary leakage of urine associated with urgency whilst stress urinary incontinence (SUI) presents as involuntary leakage with sneezing or coughing. 2 Women with obesity have a 3-fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). 7,8 In women with obesity, weight loss interventions have been shown to reduce the frequency of UI. [9][10][11] Currently, clinical guidance bodies such as the National Institute for Health and Care Excellence (NICE) and the European Association of Urology (EAU) recommend life-style intervention as the first-line treatment for women with UI and a BMI ≥30 kg/m 2.12 This encompasses the advice of weight loss through dietary, pharmacological, behavioural therapy interventions, or a combination of these. 12 Bariatric surgery, including Roux-en-Y gastric bypass (RYBG), Laparoscopic Adjustable Gastric Band (LAGB) and Laparoscopic Vertical Sleeve Gastrectomy (LVSG), is a common intervention to treat morbid obesity (BMI ≥40 kg/m 2 ), 13 but can be an appropriate measure for individuals with a BMI ≥35 kg/m 2 and related co-morbidities such as diabetes and hypertension. Although behavioural intervention studies have shown to produce statistically significant weight loss in participants, 14 bariatric surgery has proven to lead to significantly greater sustained weight loss in patients with obesity compared to non-surgical alternatives. 15 This systematic review and meta-analysis were carried out in order to compare and understand better the effects of surgical and non-surgical weight loss interventions for female obesity-related UI.

| METHODOLOGY
This protocol was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P), and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. 16 This systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews) with ID number 222714. Our key MeSH (Medical Subject Heading) search terms were; "weight loss surgery" OR "bariatric surgery" OR "metabolic surgery" OR "weight What is known on the subject?

| Search strategy
• Obesity is a recognized risk factor for UI • Weight loss has proven to reduce UI and is currently recommended in the form of behavioural interventions.
• Bariatric surgery is known to lead to greater, sustained weight loss in individuals compared to conservative weight loss methods.

What does this study add?
• This study aims to clarify the effects of surgically induced weight loss on urinary incontinence and put forward recommendations for further areas of research.
Moreover, reference lists of selected articles and other literature sources were browsed to ensure a comprehensive literature search was completed. None of the database searches filtered results based on year of publication date, and the last search was carried out in September 2020.

| Study selection
Single case reports, expert opinion manuscripts, letters to the editor, commentaries, conference papers, animal studies, meta-analyses, narrative review articles and articles not in English were excluded. Data were only included on adult (18 years or older), non-pregnant women.
Articles were included if they examined the effect of any weight loss intervention on UI. No restrictions were made regarding the intervention type, where a study took place, the number of participants or the duration of follow up. Covidence Software was used to manage the study selection process. Publications were initially screened for any duplicates before being assessed independently and in parallel by two reviewers. Any conflicts regarding the inclusion of a study were met with discussion and consensus. If an agreement had not been reached, arbitration by a third reviewer would have been required.

| Data extraction
Data were extracted independently by three reviewers following Cochrane Public Health Group Data Extraction and Assessment Template to construct our own data extraction template that was pilottested and systematically used for each article. Data extracted included; study description (eg, title, primary author, publication year, type of study, number of participants, type of weight loss intervention, and follow-up duration), participant demographics (eg, mean age), pre-and post-weight loss intervention anthropometric parameters (mean weight, mean BMI), UI assessment (eg, types of UI assessed, validated questionnaire[s] used), overall diagnosis (urodynamic tests and UI severity rating), quality of life assessments (scores of validated questionnaires). The primary outcomes were the prevalence of total UI, SUI and UUI before and after weight loss intervention.

| Quality assessment
Each study was assessed for bias using the Newcastle-Ottawa scale.
Studies were evaluated on eight factors, categorized into three groups: selection (including whether the cohort is representative of the population), comparability (assessed on grounds of study design and the analysis performed) and outcome (ie, the assessment of outcome, follow-up rate and adequacy follow-up period).
Stars were awarded per category, with a maximum of four, two and three stars possible for the ''selection'', 'comparability' and 'outcome' categories respectively. By following the guidelines of the Newcastle-Ottawa scale, 17 two reviewers assessed the studies to be of poor (3 stars or less), fair (4-6 stars), or good (7-9 stars) quality.

| Data synthesis and statistical analysis
All meta-analytical calculations were performed using MedCalc, the same software was used for generating forest plots. Pooled odds ratios (OR) were calculated with 95% confidence intervals (CI) from the extracted data with count data, while pooled standardized mean differences were calculated from the extracted continuous variables, also with 95% CI. The DerSimonian-Laird random-effects model was used in all calculations. Heterogeneity was assessed using Cochran's Q and I 2 statistics. Subgroup analyses with respect to the type of weight loss intervention were also performed for BMI and weight change differences as well as the count data variables where at least two subgroup data were available. Publication bias was assessed by using Egger's and Begg's tests along with a visual evaluation of the funnel plots when at least ten studies were available.

| RESULTS
Of the 702 references imported for screening, 157 duplicates were removed, leaving 545 articles to be screened against title and abstract, which resulted in 69 papers progressing to a full-text assessment. Due to one sample of patients from the PRIDE study being reported in 5 different articles 10,11,[18][19][20] only Subak et al. 18 was included in the meta-analysis as this paper reported the outcomes of interest of the present study from the first follow up date.
The same decision was made for other articles that reported on one sample of patients, including Treacy et al. 21 and Mazoyer et al., 22 along with Leshem et al. 22 and Shimonov et al. 23 The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) flow diagram is shown in Figure 1, outlining the outcomes of the screening process.          Whilst the underlying pathophysiology of UI is multifactorial and its aetiology not completely known, obesity is a recognized risk factor, 6,33,55,56 and a dose-response relationship between increased weight and UI incidence has been observed. 7 A study by Noblet et al.

| DISCUSSION
showed a strong correlation between BMI, intra-abdominal pressure and intravesical (bladder) pressure, with a Pearson correlation coefficient value of 0.76 and 0.71, respectively, both p < .0001. 57 It was hypothesised that this increased intra-abdominal pressure increases stress on pelvic floor organs and supporting structures, and that such stress is responsible for the symptoms presented in SUI. 57 Similarly, an increase in abdominal pressure as a result of increased abdominal adiposity, may also be responsible for detrusor instability (detrusor muscle overactivity) which can cause the symptoms of urgency that present in UUI. 9 A cohort study examining the effects of surgical weight loss interventions highlighted that reduced abdominal adiposity was associated with significant decreases in urinary bladder pressure. 58 The effects of reduced bladder pressure and SUI were observed by Bump et al., in whose study, patients' intravesical pressure readings were significantly improved at follow-up and associated with a resolution in SUI in 7 of the 10 patients who complained of SUI at baseline. 33 Traditional management of UUI can include bladder retraining and lifestyle changes, which typically advise avoidance of bladder irritants and reducing overall fluid intake. 59 Both carbonated drinks and caffeinated beverages are considered to be bladder irritants. 60,61 Following bariatric surgery, patients are advised to avoid bladder irritants and drinking fluids with meals. 62 In a similar way, the dietary changes promoted in behavioural studies involve reduced calorie intake, which is likely to be associated with reduced fluid intake. The The impact on UI severity following weight loss was only reported in four of the included studies assessing bariatric surgery as an intervention. In each, the number of participants experiencing severe UI decreased significantly. 35 Adverse effects were not reported in any behavioural studies and only discussed in one study assessing bariatric surgery. 30 Adverse effects of bariatric surgery are well established and vary depending on the type of procedure carried out. Identifying all associated adverse effects is beyond the scope of this study but should nevertheless be taken into account if bariatric surgery is to be considered as a treatment option. In addition, the short-term cost of bariatric surgery, although beyond the scope of this review, is something to be considered. However, by preventing long-term complications of UI and other obesity-related comorbidities, it would likely prove cost effective in the long-term. 64 The limitations of the present study include a disproportionally small number of controlled studies assessing surgical weight loss interventions on UI, compared to a large number of behavioural weight loss intervention studies most of which were randomized control trials. This highlights a paucity of randomized controlled trials evaluating the effects of surgical weight loss interventions on female obesity related IU. The lack of comparison groups suggests the evidence provided by these manuscripts may be of low certainty. subject to patient response bias and their ability to accurately remember and complete these forms of assessment. 65

| CONCLUSION
This is the first meta-analysis to study both bariatric surgery and behavioural weight loss interventions and their effects on UI, SUI, and UUI. Across all studies, weight loss was observed to be beneficial in improving UI. Specifically, bariatric surgery was associated with significantly reduced UI prevalence and sustained weight loss compared with behavioural interventions. The implication of these results from this study is that weight loss is an effective treatment for UI management in women with obesity. The authors of this paper recommend that more large-scale trials, with more robust study designs, are carried out to determine the relationship (linear or otherwise) between the degree of weight loss and impact on UI, and assess whether bariatric surgery should be offered to women with obesity-related UI, if other non-surgical UI management options have failed.