obesity reviews
doi: 10.1111/obr.12170
Treatment/Obesity Comorbidity
The effect of non-surgical weight loss interventions on urinary incontinence in overweight women: a systematic review and meta-analysis D. Vissers1, H. Neels1,2, A. Vermandel1,2, S. De Wachter1,2, W. A. A. Tjalma1,2, J-J. Wyndaele1,2 and J. Taeymans3
1
Faculty of Medicine and Health Sciences,
University of Antwerp, Antwerp, Belgium; 2
Multidisciplinary Pelvic Floor Clinic, Antwerp
University Hospital, Edegem, Belgium; 3
Department of Health, Bern University of
Applied Sciences, Bern, Switzerland
Received 6 December 2013; revised 3 March 2014; accepted 4 March 2014
Address for correspondence: Professor D Vissers, Faculty of Medicine and Health Sciences, University of Antwerp, Van Aertselaerstraat 31, Merksem B-2170, Belgium. E-mail: [email protected]
Summary Although the aetiology of urinary incontinence can be multifactorial, in some cases weight loss could be considered as a part of the therapeutic approach for urinary incontinence in people who are overweight. The objective of this study was to review and meta-analyse the effect of non-surgical weight loss interventions on urinary incontinence in overweight women. Web of Science, PubMed, Pedro, SPORTDiscus and Cochrane were systematically searched for clinical trials that met the a priori set criteria. Data of women who participated in non-surgical weight loss interventions (diet, exercise, medication or a combination) were included in the meta-analysis. After removing duplicates, 62 articles remained for screening on title, abstract and full text. Six articles (totalling 2,352 subjects in the intervention groups) were included for meta-analysis. The mean change in urinary incontinence (reported as frequency or quantity, depending on the study) after a non-surgical weight loss intervention, expressed as standardized effect size and corrected for small sample sizes (Hedges’ g), was −0.30 (95%CI = −0.47 to −0.12). This systematic review and meta-analysis shows evidence that a nonsurgical weight loss intervention has the potential to improve urinary incontinence and should be considered part of standard practice in the management of urinary incontinence in overweight women. Keywords: Meta-analysis, obesity, urinary incontinence, weight loss. obesity reviews (2014) 15, 610–617
Introduction The most common types of urinary incontinence (UI) are stress UI (complaint of involuntary leakage on effort or exertion, or on sneezing or coughing) and urge UI (complaint of involuntary leakage accompanied by or immediately preceded by urgency) or a mixture of both (1). All subtypes of UI have a significant impact on health-related quality of life (2). The prevalence of UI differs according to age and pregnancy or parity status. Eleven per cent of the nulliparous women and 23.5% of women older than 40 years reported incontinence (3,4). 610 15, 610–617, July 2014
Both in Europe and the United States, obesity (body mass index [BMI] ≥ 30.0 kg·m−2) has increased over the past decades, with a prevalence value in women up to 36.5% (5,6). Obesity is associated with an increased mortality risk and an increased risk of (co)morbidities such as cardiovascular disease and diabetes type 2 (7,8). Epidemiological studies showed that obesity is a strong and independent risk factor for UI and pelvic floor disorder. For example, a 20–70% increase in the UI risk for each 5-unit increase in BMI has been observed (9,10). Abdominal obesity, in particular, seems to be associated with UI (11). Increased intraabdominal pressures in obese women may increase pelvic
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floor tension stress, thereby contributing to the development of UI (12). Obesity can affect the conduction in the median nerve and increase the risk for lumbar intervertebral disc herniation and thus affect the genitourinary tract through a neurophysiological pathway (13). Because overweight and obesity may be part of the aetiological pathway of UI, it seems reasonable to assume that weight loss could be part of the treatment in some cases. It should, however, be kept in mind that overweight is one of many possible risk factors contributing to UI, along with multiparity, hormonal imbalance, neuromuscular dysfunction or trauma, and pelvic operations (14–16). Moreover, overweight is sometimes considered a contraindication for surgical treatment of UI because of a higher failure rate in obese patients undergoing retropubic suspensions (17). There is evidence that weight loss strategies using dietary, physical activity or behavioural interventions can produce significant improvements in weight (18,19). Exercise has also been proven effective in reducing visceral adipose tissue (VAT) (20). It has been described that surgically induced weight loss can have positive effects on UI (21–23). However, the purpose of this systematic review and metaanalysis was to screen literature to determine the effect of non-surgical weight loss methods on UI in overweight women.
Methods
611
were: mean age older than 18 years and a mean BMI at baseline of 25.0 kg·m−2 or higher. Data of study arms with participants receiving a non-surgical weight loss intervention (including diet, exercise, pharmaceutical weight loss or a combination) were included in the meta-analysis.
Data sources and search strategies Web of Science, PubMed, Pedro, SPORTDiscus and Cochrane were systematically searched using the following search terms (adapted for each database): (‘Body Weight Changes’ OR ‘Weight Loss’) AND ‘Urinary Incontinence’. Studies published in English from January 1995 to January 2014 were included. Reference lists of included studies were screened for relevant studies. In case of missing data or information, the corresponding authors were contacted.
Screening and data extraction form The articles that remained after removing the duplicates were independently screened by two researchers (DV, JT) on title, abstract and full text. Study eligibility disagreements were resolved through consensus. Primary outcome measures such as results from voiding diaries, questionnaires and a pad test for UI were collected. In case of a pad test, a weighted absorbent pad is worn. When urinary leakage occurs, the soiled pad is reweighted.
The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was used as a guideline in writing this systematic review and meta-analysis (24). The systematic review was submitted to the PROSPERO register (Registration No. CRD42013004063).
Risk of bias
Study selection
Statistical analysis
Clinical trials, both randomized and non-randomized, that met the a priori set criteria were included. These criteria
A meta-analysis with an a priori specified random-effects model was performed to estimate the overall weighted
The risk of bias of each eligible study was assessed by two independent reviewers (DV, JT) using the Cochrane Collaboration’s Tool for assessing risk of bias. Again, disagreements were resolved through consensus (Table 1).
Table 1 Risk of bias assessment Selection bias
Phelan et al. (54) Wing et al. (25) Wing et al. (26) Subak et al. (27) Auwad et al. (28) Brown et al. (29) Subak et al. (38) Subak et al. (35)
Performance bias
Attrition bias
Reporting bias
Random sequence generation
Allocation concealment
Blinding of participants and personnel
Addressing incomplete outcome data
Selective reporting
Other bias
+ + + + − + + −
− + + + − + + −
+ + + + − − + −
+ + + + − + + +
+ + + + + + + +
+ + + + ? ? + ?
‘+’ denotes ‘Low risk of bias’; ‘?’ denotes ‘Unclear’; ‘−’ denotes ‘High risk of bias’.
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mean effect size. Effect sizes, extracted from the individual studies, were expressed as standardized mean differences and were corrected for small study bias of overestimating the true effect size using Hedges’ g. The 95% confidence intervals (95%CI) around the effect sizes were established. Heterogeneity across studies was tested by calculation of the Cochran’s Q statistic and its corresponding P value. Higgins’ I2 was calculated and expressed in per cent to assess the degree of heterogeneity, i.e. to explain the part of the total observed variability that can be explained by true between-studies variability. Publication bias was not assessed given the fact that only six studies were included in the meta-analysis. All statistical analyses were performed using the CMA-2 software (Comprehensive Meta-Analysis 2nd version, Biostat, Englewood, NJ, USA). The limit for statistical significance was set at P = 0.05.
Results Overview of included studies for the meta-analysis
Identification
After removing duplicates, 62 articles remained. After screening on title, abstract and full text, six articles (totalling 2,352 subjects in the intervention groups) were included for meta-analysis (Fig. 1). The risk of bias assess-
Records identified through database searching (n = 79)
ment of the controlled and two non-controlled studies (Auwad et al. (28) and Subak et al. (35)) is shown in Table 1.
Meta-analysis Table 2 shows an overview of the data extracted from the included studies. Eight studies were included for the risk of bias analysis. Because the group of Subak et al. reported on the same sample in three different studies (25–27), only the article that presented the effect size directly after the intervention ended (i.e. after 6 months) was withheld for further analysis. Therefore, only six studies were finally included in the meta-analysis. The standardized mean change (Hedges’ g) in UI after a non-surgical weight loss intervention was −0.30 (95%CI = −0.47 to −0.12) (Fig. 2) with a Z-value of −3.37 (P < 0.001; two tailed). There was a significant and high heterogeneity between studies (Cochran’s Q = 18.31; degrees of freedom of Q (df(Q)) = 5; P = 0.003; I2 = 72.69%). The study of Subak et al. found a more important effect size (Hedges’ g = −1.18) compared with the five other studies under investigation in the present meta-analysis (Hedges’ g ranged from −0.51 to −0.09). To test the robustness of the overall estimate against this single high effect
Additional records identified through other sources (n = 0)
Eligibility
Screening
Records after duplicates removed (n = 62)
Records screened (n = 62)
Records excluded (n = 44)
Full-text articles assessed for eligibility (n = 18)
Full-text articles excluded, because urinary incontinence was not the primary outcome parameter. (n = 10)
Included
Studies included in qualitative synthesis (n = 8)
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Studies included in quantitative synthesis (meta-analysis) (n = 6)
Figure 1 Four-phase flow diagram of the systematic reviewing process.
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338
64
1,957
48
20
Subak et al. (27)
Auwad et al. (28)
Brown et al. (29)
Subak et al. (38)
Subak et al. (35)
34 (IQR 32–40)
38 ± 10
52 (IQR 47–59)
48.1 ± 10.5
34.9 ± 6.9
50 ± 10
Intervention: 36 ± 6 Control: 36 ± 5
53 ± 11
36.2
36.5 ± 6.1
57.9 ± 6.8
52.5
BMI (kg m–2)
Age (years)
1.3 ± 1.1
Median: 1 IQR (0–2)
None: 89 (5.3%) One: 292 (17.5%) Two: 588 (35.3%) ≥3: 698 (41.9%)
Median: 2 (IQR 2–3)
NA
Parity > 2 70% (ILI) 71% (DSE)
Parity (0,1,multi)
A 7-d voiding diary
7-d voiding diary Primary outcome: % change in number of weekly urinary incontinent episodes
Self-administered questionnaire modified from validated questions
24-h pad test Perineal ultrasound to assess bladder neck mobility Pelvic floor muscle strength
7-d voiding diary Recording of incontinence episodes Pad test
Validated self-report questions Weekly or more frequent incontinent episodes
Assessment UI
Low-calorie liquid or a reduced-calorie solid diet, exercise and behavioural modification (n = 10)
3-month liquid diet weight reduction program, exercise and behavioural modification (n = 24)
660 (34%) intensive lifestyle therapy (ILI) 636 (32%) to metformin (MET)
Commercially run program of diet and exercise
6-month behavioural weight loss program (n = 226)
Intensive lifestyle weight loss intervention (ILI; n = 1,385)
Intervention
No control group
Wait list delayed intervention group (n = 24)
3m (range 2–6)
3m
Mean 2.9 years
18 m
No control group
661 (34%) to placebo with standard lifestyle advice
6m
1 year
Duration
Structured education program (n = 112)
DSE; n = 1,354
Control group
15 ± 18 kg
Intervention group: −16 kg (IQR −9 to −20) Wait list control group: 0 kg (IQR −2 to 2) (P < 0.0001)
Reduction in weekly UI episodes: from 13 (± 10) per week at baseline to 8 (± 10) per week on completion
Reduction in weekly UI episodes Intervention group: 60% (IQR 30–89%) in weekly UI episodes Wait list control group: 15% (IQR −9% to 25%) (P < 0.0005)
Fewer women in the ILI had weekly incontinence compared with women in the MET or placebo groups (38.3% vs. 48.1% vs. 45.7%, respectively, P = 0.001) Women randomized to ILI had significantly lower odds of weekly UI compared with women assigned to placebo (OR 0.76 [95% CI 0.61–0.95])
Pad weight (g): median (25–75% IQR) baseline vs. post weight loss 38.75 (27.00–69.00) vs. 18.50 (8.63–34.88); P < 0.001
≥10%: n = 20 ≥ 5%: n = 22 25.3% DSE: 26.7% to >28.6%
Change in total UI
% change (95% CI) after 6 months Intervention group: −8.0 (−9.0, −7.0) Control group: −1.6 (−2.7, −0.4)
After 1 year: ILI: −7.7 kg DSE: −0.7 kg
Weight loss
Weight loss and urinary incontinence
BMI, body mass index; DSE, Diabetes Support and Education; ILI, intensive lifestyle intervention; IQR, interquartile range; NA, not applicable; UI, urinary incontinence.
2,739
Phelan et al. (54)
N
Table 2 Overview of the studies included in the meta-analysis
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Figure 2 Forest plot of the effects found in the individual studies and the overall effect.
size, a sensitivity analysis was conducted. After excluding the Subak et al. data from the meta-analysis, the overall weighted mean estimate decreased from −0.30 to −0.22 (Hedges’ g) with a 95%CI ranging from −0.35 to −0.09, and hence remained significant (P = 0.001). Betweenstudies heterogeneity decreased towards Cochran’s Q = 9.23 and became not significant (df(Q) = 4, P = 0.056; I2 = 56.7%). A subgroup analysis for study type was conducted. The overall weighted estimate (Hedges’ g) of the two non-controlled studies in pre-post design (Auwad et al. and Subak et al.) was −0.49 (95%CI = −0.85 to −0.14) with a Z-value of −2.74 (P < 0.006; two tailed). The overall weighted estimate (Hedges’ g) of the remaining four controlled studies was −0.23 (95%CI = −0.40 to −0.06) with a Z-value of −2.63 (P < 0.008; two tailed).
Discussion To the best of our knowledge, this systematic review and meta-analysis is the first to investigate the effect of nonsurgical weight loss methods on UI in overweight women. No articles on the effect of pharmacological-induced weight loss on UI could be identified. However, in the study of Auwad et al., participants in the intervention group received orlistat if they did not manage to lose 5% of their initial weight after 9 months (28). The authors reported that most participants required their diet and exercise program to be supplemented with orlistat to achieve a 5% weight loss. The primary function of orlistat is to prevent the absorption of fats by acting as a lipase inhibitor. In the study of Brown et al., there was a group who received metformin, but the results of this arm of study were not included in this meta-analysis (29). Metformin is primarily an anti-diabetic drug with a secondary weight-neutral or moderate weight-sparing effect, with meta-analyses showing no difference in weight loss between metformin and placebo (30).
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The results of the present meta-analysis indicate evidence for an improvement in UI in overweight and obese women who participated in a weight loss intervention. Modest weight loss can yield important health benefits (31). Indeed, most studies included in the meta-analysis aimed for 5–10% weight loss, which was achieved by a behavioural program that combined diet and exercise. As described by Wing et al., there is a higher success rate in reducing UI episodes in women who achieve a 5–10% weight loss with an indication that more weight loss will not necessarily lead to more improvement in UI episodes (26). However, in the present meta-analysis, the study with largest mean effect size (Subak et al.) was also the study in which women had the highest mean weight loss. Women were placed on a very low-calorie diet of 800 kcal d–1 or less, which explains the degree of weight loss. It should be noted that this was a study with a relatively small sample size, hence the small relative weight and large confidence interval. In total, six studies were included in the presented metaanalysis. It has been well described that small studies tend to overestimate the true effect size (32–34). The smallest study in this meta-analysis included 10 participants (35). Because of this small sample size, the overall effect size may have been pulled to the left on the forest plot, overestimating the effect of weight loss on UI in overweight and obese women. The sensitivity analysis showed, however, that even after excluding the data from the meta-analysis, the overall effect size decreased but remained (clinically) important and statistically significant. Two of the studies were not controlled studies with pre-post design. As was expected, the subgroup analysis for study design showed a higher effect size in the non-controlled compared with the controlled studies. Some studies used a pad test to assess UI (expressed in mg) while other studies used the number of self-reported UI incidences per week as primary outcome parameter. Some studies considered the 24-h involuntary urine loss
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determined by a pad test, a secondary outcome. Although there were significant improvements in the primary outcome measure (self-reported UI incidences per week) after 6 months in the intervention group compared with the control group, this was not the case for the (unpublished) secondary outcome parameter. The 24-h involuntary urine loss determined by a pad test improved in both the intervention and the control groups. The effect of a lifestyle intervention program targeting weight loss on UI can possibly be explained not only by a number of conventional risk factors associated with overweight, but also by some more novel risk factors. It has been hypothesized that obesity increases abdominal pressure, thereby stressing the pelvic floor and contributing to UI (36,37). Abdominal pressure could also contribute to UI by causing detrusor instability (38). Obesity may also be associated with neurogenic disease that could have an impact on pelvic floor and urethral dysfunction (13). It has been demonstrated that weight loss induced by bariatric surgery can improve UI in up to 82% of patients (39,40). Abdominal adiposity has been described as an independent risk factor for UI in women (41). VAT is now recognized to be a pathogenic ectopic storage of fat (42,43). It has become clear that adipocytokines do not only play a role in energy homeostasis but also in insulin resistance, diabetes and inflammation, linking obesity to premature atherosclerosis (44,45). This has brought a new aspect to the association between obesity and UI. Recently, the role of insulin resistance in the overactive bladder was reported in mice and humans (46,47). Furthermore, a role for inflammation in the overactive bladder was described, as well as the occurrence of chronic low-grade inflammation in the bladder of obese women (41,48). Adipocytes surrounding the human bladder can be affected, thus leading to inflammation. Linking obesity to a so-called adipose tissue disease (adiposopathy), or lipotoxicity hypothesis, brings novel risk factors that may explain the association between overweight and UI (49). Adipose tissue in obese people is characterized by an increased presence of dead adipocytes that attract macrophages secreting inflammation mediators (50). Furthermore, obesity in women is characterized by a decrease in ghrelin levels (51). Ghrelin is an appetite-regulating peptide that is produced mainly in the stomach. This decrease in ghrelin levels in obese women could increase the risk of UI by having an adverse effect on detrusor contractility and urethral support (52,53).
Study strengths and limitations There are some limitations of this review that need to be acknowledged. Most studies did not report a power measurement or sample size calculation. Only few studies assessed compliance to the lifestyle program. The limited © 2014 The Authors obesity reviews © 2014 World Obesity
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number of studies is also the reason why no subgroup analysis for stress, urge or mixed incontinence was done. Furthermore, different types of UI were used in different studies: stress UI, urge UI, mixed UI, other UI and detrusor overactivity incontinence. Conclusions on improvement per type of UI differed: two studies reported significant improvement in stress UI, but not in urgency UI (Phelan et al. and Subak et al.); three studies reported significant improvement in all types of UI (Auwad et al., Brown et al. and Subak et al.); and one study reported a significant improvement in weekly incontinence episodes but could not observe a significant improvement by specific type of incontinence (Subak et al.). The strength of this meta-analysis is that it is the first to focus on the effects of non-surgical weight loss interventions on UI in overweight women and provides in that way information that could be of potential importance for a multidisciplinary approach of UI therapy in overweight women.
Conclusion There are but few studies that report on the effect of weight loss interventions on UI in women. This meta-analysis shows evidence that a non-surgical weight loss intervention (diet, exercise, medication or combination) has the potential to improve UI and should be considered part of standard practice in the management of UI in overweight women. Recommendations for future high-quality large-scaled trials are to assess UI using an objective method such as a pad test to take possible confounding factors (such as multiparity, oestrogen deficiency and pelvic operations) into account and to carefully assess compliance to the weight loss program.
Conflict of interest statement The authors declare no conflicts of interest.
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49. Oda E. The metabolic syndrome as a concept of adipose tissue disease. Hypertens Res 2008; 31: 1283–1291. 50. Surmi BK, Hasty AH. Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Future Lipidol 2008; 3: 545–556. 51. Vicennati V, Genghini S, De Iasio R, Pasqui F, Pagotto U, Pasquali R. Circulating obestatin levels and the ghrelin/obestatin ratio in obese women. Eur J Endocrinol 2007; 157: 295–301. 52. Whitcomb LE, Subak LL. Effect of weight loss on urinary incontinence in women. Open Access J Urol 2011; 3: 123–132. 53. Rizk DE, Fahim MA. Ageing of the female pelvic floor: towards treatment a la carte of the ‘geripause’. Int Urogynecol J Pelvic Floor Dysfunct 2008; 19: 455–458. 54. Phelan S, Kanaya AM, Subak LL et al. Weight loss prevents urinary incontinence in women with type 2 diabetes: results from the Look AHEAD trial. J Urol 2012; 187: 939–944.
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doi: 10.1111/obr.12170
Treatment/Obesity Comorbidity
The effect of non-surgical weight loss interventions on urinary incontinence in overweight women: a systematic review and meta-analysis D. Vissers1, H. Neels1,2, A. Vermandel1,2, S. De Wachter1,2, W. A. A. Tjalma1,2, J-J. Wyndaele1,2 and J. Taeymans3
1
Faculty of Medicine and Health Sciences,
University of Antwerp, Antwerp, Belgium; 2
Multidisciplinary Pelvic Floor Clinic, Antwerp
University Hospital, Edegem, Belgium; 3
Department of Health, Bern University of
Applied Sciences, Bern, Switzerland
Received 6 December 2013; revised 3 March 2014; accepted 4 March 2014
Address for correspondence: Professor D Vissers, Faculty of Medicine and Health Sciences, University of Antwerp, Van Aertselaerstraat 31, Merksem B-2170, Belgium. E-mail: [email protected]
Summary Although the aetiology of urinary incontinence can be multifactorial, in some cases weight loss could be considered as a part of the therapeutic approach for urinary incontinence in people who are overweight. The objective of this study was to review and meta-analyse the effect of non-surgical weight loss interventions on urinary incontinence in overweight women. Web of Science, PubMed, Pedro, SPORTDiscus and Cochrane were systematically searched for clinical trials that met the a priori set criteria. Data of women who participated in non-surgical weight loss interventions (diet, exercise, medication or a combination) were included in the meta-analysis. After removing duplicates, 62 articles remained for screening on title, abstract and full text. Six articles (totalling 2,352 subjects in the intervention groups) were included for meta-analysis. The mean change in urinary incontinence (reported as frequency or quantity, depending on the study) after a non-surgical weight loss intervention, expressed as standardized effect size and corrected for small sample sizes (Hedges’ g), was −0.30 (95%CI = −0.47 to −0.12). This systematic review and meta-analysis shows evidence that a nonsurgical weight loss intervention has the potential to improve urinary incontinence and should be considered part of standard practice in the management of urinary incontinence in overweight women. Keywords: Meta-analysis, obesity, urinary incontinence, weight loss. obesity reviews (2014) 15, 610–617
Introduction The most common types of urinary incontinence (UI) are stress UI (complaint of involuntary leakage on effort or exertion, or on sneezing or coughing) and urge UI (complaint of involuntary leakage accompanied by or immediately preceded by urgency) or a mixture of both (1). All subtypes of UI have a significant impact on health-related quality of life (2). The prevalence of UI differs according to age and pregnancy or parity status. Eleven per cent of the nulliparous women and 23.5% of women older than 40 years reported incontinence (3,4). 610 15, 610–617, July 2014
Both in Europe and the United States, obesity (body mass index [BMI] ≥ 30.0 kg·m−2) has increased over the past decades, with a prevalence value in women up to 36.5% (5,6). Obesity is associated with an increased mortality risk and an increased risk of (co)morbidities such as cardiovascular disease and diabetes type 2 (7,8). Epidemiological studies showed that obesity is a strong and independent risk factor for UI and pelvic floor disorder. For example, a 20–70% increase in the UI risk for each 5-unit increase in BMI has been observed (9,10). Abdominal obesity, in particular, seems to be associated with UI (11). Increased intraabdominal pressures in obese women may increase pelvic
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floor tension stress, thereby contributing to the development of UI (12). Obesity can affect the conduction in the median nerve and increase the risk for lumbar intervertebral disc herniation and thus affect the genitourinary tract through a neurophysiological pathway (13). Because overweight and obesity may be part of the aetiological pathway of UI, it seems reasonable to assume that weight loss could be part of the treatment in some cases. It should, however, be kept in mind that overweight is one of many possible risk factors contributing to UI, along with multiparity, hormonal imbalance, neuromuscular dysfunction or trauma, and pelvic operations (14–16). Moreover, overweight is sometimes considered a contraindication for surgical treatment of UI because of a higher failure rate in obese patients undergoing retropubic suspensions (17). There is evidence that weight loss strategies using dietary, physical activity or behavioural interventions can produce significant improvements in weight (18,19). Exercise has also been proven effective in reducing visceral adipose tissue (VAT) (20). It has been described that surgically induced weight loss can have positive effects on UI (21–23). However, the purpose of this systematic review and metaanalysis was to screen literature to determine the effect of non-surgical weight loss methods on UI in overweight women.
Methods
611
were: mean age older than 18 years and a mean BMI at baseline of 25.0 kg·m−2 or higher. Data of study arms with participants receiving a non-surgical weight loss intervention (including diet, exercise, pharmaceutical weight loss or a combination) were included in the meta-analysis.
Data sources and search strategies Web of Science, PubMed, Pedro, SPORTDiscus and Cochrane were systematically searched using the following search terms (adapted for each database): (‘Body Weight Changes’ OR ‘Weight Loss’) AND ‘Urinary Incontinence’. Studies published in English from January 1995 to January 2014 were included. Reference lists of included studies were screened for relevant studies. In case of missing data or information, the corresponding authors were contacted.
Screening and data extraction form The articles that remained after removing the duplicates were independently screened by two researchers (DV, JT) on title, abstract and full text. Study eligibility disagreements were resolved through consensus. Primary outcome measures such as results from voiding diaries, questionnaires and a pad test for UI were collected. In case of a pad test, a weighted absorbent pad is worn. When urinary leakage occurs, the soiled pad is reweighted.
The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was used as a guideline in writing this systematic review and meta-analysis (24). The systematic review was submitted to the PROSPERO register (Registration No. CRD42013004063).
Risk of bias
Study selection
Statistical analysis
Clinical trials, both randomized and non-randomized, that met the a priori set criteria were included. These criteria
A meta-analysis with an a priori specified random-effects model was performed to estimate the overall weighted
The risk of bias of each eligible study was assessed by two independent reviewers (DV, JT) using the Cochrane Collaboration’s Tool for assessing risk of bias. Again, disagreements were resolved through consensus (Table 1).
Table 1 Risk of bias assessment Selection bias
Phelan et al. (54) Wing et al. (25) Wing et al. (26) Subak et al. (27) Auwad et al. (28) Brown et al. (29) Subak et al. (38) Subak et al. (35)
Performance bias
Attrition bias
Reporting bias
Random sequence generation
Allocation concealment
Blinding of participants and personnel
Addressing incomplete outcome data
Selective reporting
Other bias
+ + + + − + + −
− + + + − + + −
+ + + + − − + −
+ + + + − + + +
+ + + + + + + +
+ + + + ? ? + ?
‘+’ denotes ‘Low risk of bias’; ‘?’ denotes ‘Unclear’; ‘−’ denotes ‘High risk of bias’.
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mean effect size. Effect sizes, extracted from the individual studies, were expressed as standardized mean differences and were corrected for small study bias of overestimating the true effect size using Hedges’ g. The 95% confidence intervals (95%CI) around the effect sizes were established. Heterogeneity across studies was tested by calculation of the Cochran’s Q statistic and its corresponding P value. Higgins’ I2 was calculated and expressed in per cent to assess the degree of heterogeneity, i.e. to explain the part of the total observed variability that can be explained by true between-studies variability. Publication bias was not assessed given the fact that only six studies were included in the meta-analysis. All statistical analyses were performed using the CMA-2 software (Comprehensive Meta-Analysis 2nd version, Biostat, Englewood, NJ, USA). The limit for statistical significance was set at P = 0.05.
Results Overview of included studies for the meta-analysis
Identification
After removing duplicates, 62 articles remained. After screening on title, abstract and full text, six articles (totalling 2,352 subjects in the intervention groups) were included for meta-analysis (Fig. 1). The risk of bias assess-
Records identified through database searching (n = 79)
ment of the controlled and two non-controlled studies (Auwad et al. (28) and Subak et al. (35)) is shown in Table 1.
Meta-analysis Table 2 shows an overview of the data extracted from the included studies. Eight studies were included for the risk of bias analysis. Because the group of Subak et al. reported on the same sample in three different studies (25–27), only the article that presented the effect size directly after the intervention ended (i.e. after 6 months) was withheld for further analysis. Therefore, only six studies were finally included in the meta-analysis. The standardized mean change (Hedges’ g) in UI after a non-surgical weight loss intervention was −0.30 (95%CI = −0.47 to −0.12) (Fig. 2) with a Z-value of −3.37 (P < 0.001; two tailed). There was a significant and high heterogeneity between studies (Cochran’s Q = 18.31; degrees of freedom of Q (df(Q)) = 5; P = 0.003; I2 = 72.69%). The study of Subak et al. found a more important effect size (Hedges’ g = −1.18) compared with the five other studies under investigation in the present meta-analysis (Hedges’ g ranged from −0.51 to −0.09). To test the robustness of the overall estimate against this single high effect
Additional records identified through other sources (n = 0)
Eligibility
Screening
Records after duplicates removed (n = 62)
Records screened (n = 62)
Records excluded (n = 44)
Full-text articles assessed for eligibility (n = 18)
Full-text articles excluded, because urinary incontinence was not the primary outcome parameter. (n = 10)
Included
Studies included in qualitative synthesis (n = 8)
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Studies included in quantitative synthesis (meta-analysis) (n = 6)
Figure 1 Four-phase flow diagram of the systematic reviewing process.
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338
64
1,957
48
20
Subak et al. (27)
Auwad et al. (28)
Brown et al. (29)
Subak et al. (38)
Subak et al. (35)
34 (IQR 32–40)
38 ± 10
52 (IQR 47–59)
48.1 ± 10.5
34.9 ± 6.9
50 ± 10
Intervention: 36 ± 6 Control: 36 ± 5
53 ± 11
36.2
36.5 ± 6.1
57.9 ± 6.8
52.5
BMI (kg m–2)
Age (years)
1.3 ± 1.1
Median: 1 IQR (0–2)
None: 89 (5.3%) One: 292 (17.5%) Two: 588 (35.3%) ≥3: 698 (41.9%)
Median: 2 (IQR 2–3)
NA
Parity > 2 70% (ILI) 71% (DSE)
Parity (0,1,multi)
A 7-d voiding diary
7-d voiding diary Primary outcome: % change in number of weekly urinary incontinent episodes
Self-administered questionnaire modified from validated questions
24-h pad test Perineal ultrasound to assess bladder neck mobility Pelvic floor muscle strength
7-d voiding diary Recording of incontinence episodes Pad test
Validated self-report questions Weekly or more frequent incontinent episodes
Assessment UI
Low-calorie liquid or a reduced-calorie solid diet, exercise and behavioural modification (n = 10)
3-month liquid diet weight reduction program, exercise and behavioural modification (n = 24)
660 (34%) intensive lifestyle therapy (ILI) 636 (32%) to metformin (MET)
Commercially run program of diet and exercise
6-month behavioural weight loss program (n = 226)
Intensive lifestyle weight loss intervention (ILI; n = 1,385)
Intervention
No control group
Wait list delayed intervention group (n = 24)
3m (range 2–6)
3m
Mean 2.9 years
18 m
No control group
661 (34%) to placebo with standard lifestyle advice
6m
1 year
Duration
Structured education program (n = 112)
DSE; n = 1,354
Control group
15 ± 18 kg
Intervention group: −16 kg (IQR −9 to −20) Wait list control group: 0 kg (IQR −2 to 2) (P < 0.0001)
Reduction in weekly UI episodes: from 13 (± 10) per week at baseline to 8 (± 10) per week on completion
Reduction in weekly UI episodes Intervention group: 60% (IQR 30–89%) in weekly UI episodes Wait list control group: 15% (IQR −9% to 25%) (P < 0.0005)
Fewer women in the ILI had weekly incontinence compared with women in the MET or placebo groups (38.3% vs. 48.1% vs. 45.7%, respectively, P = 0.001) Women randomized to ILI had significantly lower odds of weekly UI compared with women assigned to placebo (OR 0.76 [95% CI 0.61–0.95])
Pad weight (g): median (25–75% IQR) baseline vs. post weight loss 38.75 (27.00–69.00) vs. 18.50 (8.63–34.88); P < 0.001
≥10%: n = 20 ≥ 5%: n = 22 25.3% DSE: 26.7% to >28.6%
Change in total UI
% change (95% CI) after 6 months Intervention group: −8.0 (−9.0, −7.0) Control group: −1.6 (−2.7, −0.4)
After 1 year: ILI: −7.7 kg DSE: −0.7 kg
Weight loss
Weight loss and urinary incontinence
BMI, body mass index; DSE, Diabetes Support and Education; ILI, intensive lifestyle intervention; IQR, interquartile range; NA, not applicable; UI, urinary incontinence.
2,739
Phelan et al. (54)
N
Table 2 Overview of the studies included in the meta-analysis
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Figure 2 Forest plot of the effects found in the individual studies and the overall effect.
size, a sensitivity analysis was conducted. After excluding the Subak et al. data from the meta-analysis, the overall weighted mean estimate decreased from −0.30 to −0.22 (Hedges’ g) with a 95%CI ranging from −0.35 to −0.09, and hence remained significant (P = 0.001). Betweenstudies heterogeneity decreased towards Cochran’s Q = 9.23 and became not significant (df(Q) = 4, P = 0.056; I2 = 56.7%). A subgroup analysis for study type was conducted. The overall weighted estimate (Hedges’ g) of the two non-controlled studies in pre-post design (Auwad et al. and Subak et al.) was −0.49 (95%CI = −0.85 to −0.14) with a Z-value of −2.74 (P < 0.006; two tailed). The overall weighted estimate (Hedges’ g) of the remaining four controlled studies was −0.23 (95%CI = −0.40 to −0.06) with a Z-value of −2.63 (P < 0.008; two tailed).
Discussion To the best of our knowledge, this systematic review and meta-analysis is the first to investigate the effect of nonsurgical weight loss methods on UI in overweight women. No articles on the effect of pharmacological-induced weight loss on UI could be identified. However, in the study of Auwad et al., participants in the intervention group received orlistat if they did not manage to lose 5% of their initial weight after 9 months (28). The authors reported that most participants required their diet and exercise program to be supplemented with orlistat to achieve a 5% weight loss. The primary function of orlistat is to prevent the absorption of fats by acting as a lipase inhibitor. In the study of Brown et al., there was a group who received metformin, but the results of this arm of study were not included in this meta-analysis (29). Metformin is primarily an anti-diabetic drug with a secondary weight-neutral or moderate weight-sparing effect, with meta-analyses showing no difference in weight loss between metformin and placebo (30).
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The results of the present meta-analysis indicate evidence for an improvement in UI in overweight and obese women who participated in a weight loss intervention. Modest weight loss can yield important health benefits (31). Indeed, most studies included in the meta-analysis aimed for 5–10% weight loss, which was achieved by a behavioural program that combined diet and exercise. As described by Wing et al., there is a higher success rate in reducing UI episodes in women who achieve a 5–10% weight loss with an indication that more weight loss will not necessarily lead to more improvement in UI episodes (26). However, in the present meta-analysis, the study with largest mean effect size (Subak et al.) was also the study in which women had the highest mean weight loss. Women were placed on a very low-calorie diet of 800 kcal d–1 or less, which explains the degree of weight loss. It should be noted that this was a study with a relatively small sample size, hence the small relative weight and large confidence interval. In total, six studies were included in the presented metaanalysis. It has been well described that small studies tend to overestimate the true effect size (32–34). The smallest study in this meta-analysis included 10 participants (35). Because of this small sample size, the overall effect size may have been pulled to the left on the forest plot, overestimating the effect of weight loss on UI in overweight and obese women. The sensitivity analysis showed, however, that even after excluding the data from the meta-analysis, the overall effect size decreased but remained (clinically) important and statistically significant. Two of the studies were not controlled studies with pre-post design. As was expected, the subgroup analysis for study design showed a higher effect size in the non-controlled compared with the controlled studies. Some studies used a pad test to assess UI (expressed in mg) while other studies used the number of self-reported UI incidences per week as primary outcome parameter. Some studies considered the 24-h involuntary urine loss
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determined by a pad test, a secondary outcome. Although there were significant improvements in the primary outcome measure (self-reported UI incidences per week) after 6 months in the intervention group compared with the control group, this was not the case for the (unpublished) secondary outcome parameter. The 24-h involuntary urine loss determined by a pad test improved in both the intervention and the control groups. The effect of a lifestyle intervention program targeting weight loss on UI can possibly be explained not only by a number of conventional risk factors associated with overweight, but also by some more novel risk factors. It has been hypothesized that obesity increases abdominal pressure, thereby stressing the pelvic floor and contributing to UI (36,37). Abdominal pressure could also contribute to UI by causing detrusor instability (38). Obesity may also be associated with neurogenic disease that could have an impact on pelvic floor and urethral dysfunction (13). It has been demonstrated that weight loss induced by bariatric surgery can improve UI in up to 82% of patients (39,40). Abdominal adiposity has been described as an independent risk factor for UI in women (41). VAT is now recognized to be a pathogenic ectopic storage of fat (42,43). It has become clear that adipocytokines do not only play a role in energy homeostasis but also in insulin resistance, diabetes and inflammation, linking obesity to premature atherosclerosis (44,45). This has brought a new aspect to the association between obesity and UI. Recently, the role of insulin resistance in the overactive bladder was reported in mice and humans (46,47). Furthermore, a role for inflammation in the overactive bladder was described, as well as the occurrence of chronic low-grade inflammation in the bladder of obese women (41,48). Adipocytes surrounding the human bladder can be affected, thus leading to inflammation. Linking obesity to a so-called adipose tissue disease (adiposopathy), or lipotoxicity hypothesis, brings novel risk factors that may explain the association between overweight and UI (49). Adipose tissue in obese people is characterized by an increased presence of dead adipocytes that attract macrophages secreting inflammation mediators (50). Furthermore, obesity in women is characterized by a decrease in ghrelin levels (51). Ghrelin is an appetite-regulating peptide that is produced mainly in the stomach. This decrease in ghrelin levels in obese women could increase the risk of UI by having an adverse effect on detrusor contractility and urethral support (52,53).
Study strengths and limitations There are some limitations of this review that need to be acknowledged. Most studies did not report a power measurement or sample size calculation. Only few studies assessed compliance to the lifestyle program. The limited © 2014 The Authors obesity reviews © 2014 World Obesity
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number of studies is also the reason why no subgroup analysis for stress, urge or mixed incontinence was done. Furthermore, different types of UI were used in different studies: stress UI, urge UI, mixed UI, other UI and detrusor overactivity incontinence. Conclusions on improvement per type of UI differed: two studies reported significant improvement in stress UI, but not in urgency UI (Phelan et al. and Subak et al.); three studies reported significant improvement in all types of UI (Auwad et al., Brown et al. and Subak et al.); and one study reported a significant improvement in weekly incontinence episodes but could not observe a significant improvement by specific type of incontinence (Subak et al.). The strength of this meta-analysis is that it is the first to focus on the effects of non-surgical weight loss interventions on UI in overweight women and provides in that way information that could be of potential importance for a multidisciplinary approach of UI therapy in overweight women.
Conclusion There are but few studies that report on the effect of weight loss interventions on UI in women. This meta-analysis shows evidence that a non-surgical weight loss intervention (diet, exercise, medication or combination) has the potential to improve UI and should be considered part of standard practice in the management of UI in overweight women. Recommendations for future high-quality large-scaled trials are to assess UI using an objective method such as a pad test to take possible confounding factors (such as multiparity, oestrogen deficiency and pelvic operations) into account and to carefully assess compliance to the weight loss program.
Conflict of interest statement The authors declare no conflicts of interest.
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