S t res s U r i n a r y Incontinence Comparative Efficacy Trials Erin Seifert Lavelle,
MD
a,
*, Halina M. Zyczynski,
MD
b
KEYWORDS Stress urinary incontinence (SUI) Treatment Comparative efficacy Review KEY POINTS Weight loss of 5% to 10% of body weight results in more than 50% reduction in weekly stress urinary incontinence episodes. Approximately half of women with stress urinary incontinence experience symptom improvement from pelvic floor muscle therapy, compared with less than 10% with expectant management, and 91% after midurethral sling. Up to half of women who receive pelvic floor muscle therapy as initial treatment of moderate to severe stress urinary incontinence subsequently pursue surgical management. Surgery offered as first-line intervention is more likely to result in continence and treatment satisfaction in a shorter interval. Both retropubic and transobturator approaches to midurethral sling are highly successful procedures for stress urinary incontinence, with high long-term patient satisfaction. Adverse event profiles differ between approaches. Patients with contraindications or aversion to surgical mesh can be reassured that a Burch colposuspension or fascial pubovaginal sling result in similar continence rates and perioperative complications compared with midurethral slings.
INTRODUCTION
Almost 16% of community dwelling women in the United States report symptoms of urinary incontinence.1 Most of these women report symptoms of stress urinary incontinence (SUI), or involuntary urine loss associated with coughing, sneezing, or other physical activity, without a preceding detrusor contraction.2–4 Some women
Disclosure: The authors have nothing to disclose. a Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA; b Division of Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA * Corresponding author. E-mail address: [email protected] Obstet Gynecol Clin N Am 43 (2016) 45–57 http://dx.doi.org/10.1016/j.ogc.2015.10.009 obgyn.theclinics.com 0889-8545/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
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experience only stress-type incontinence, whereas many others report additional leakage symptoms such as urgency urinary incontinence (UUI), or leakage following a sudden and urgent need to void secondary to detrusor spasm. The combination of incontinence mechanisms is referred to as mixed urinary incontinence (MUI). SUI results in significant personal and financial burden for symptomatic women. Threequarters of women who experience SUI report significant bother from their symptoms, and an estimated 13.6% of American women elect to undergo surgical treatment of SUI.5 Management strategies to reduce the burden of SUI include behavioral changes, weight reduction, pelvic floor muscle therapy (PFMT), and various surgical interventions. This article reviews the highest-quality clinical trials comparing contemporary treatment options for women with SUI. When available, results from large multicenter randomized controlled trials (RCTs) are highlighted. In their absence, results from smaller and single-site RCTs are reported, acknowledging their limitations. Clinicians and patients can use this compendium of the highest-quality studies to inform their treatment selection. For each trial, the population characteristics, number of participants, intervention, primary outcome, and notable secondary outcomes are presented. Where systematic reviews or meta-analyses are available, their findings are included as well. NONSURGICAL MANAGEMENT FOR STRESS URINARY INCONTINENCE
Nonsurgical management strategies targeting SUI offer patients the potential for symptom improvement while avoiding the risk of surgical morbidity, such as perioperative complications, postoperative voiding dysfunction, or mesh exposure. The interventions in this class use behavior or lifestyle modifications such as bladder training, fluid management, and weight loss. Physical therapy targeting optimization of pelvic floor function, often referred to as PFMT, and incontinence pessaries are adjuvants to behavioral modifications. Outcomes of these strategies, used individually or in combination as first-line therapy, were investigated in several randomized trials. Fluid management, a keystone of behavior intervention for bladder symptoms, entails moderating total fluid intake and specifically bladder irritants such as caffeine and alcohol. Fluid management has not been addressed in a clinical trial for SUI treatment. Remaining treatments are addressed later. Weight Loss
Overweight and obese women who lose 5% to 10% of their body weight can expect significant improvement in SUI. Obesity is a risk factor for incontinence and imparts a 3-fold to 4-fold risk for SUI.6,7 Sustained weight reduction among obese and morbidly obese women has shown substantial improvement in their incontinence symptoms in 2 large trials. The Program to Reduce Incontinence by Diet and Exercise (PRIDE) study randomized 338 women to an intensive 6-month behavioral weight loss program versus a control treatment of 4 educational sessions on weight loss and healthy diet.8 Both groups received an instruction booklet describing pelvic floor strengthening, incontinence suppression techniques, and bladder diaries. The primary outcome was weekly episodes of SUI reported by bladder diary at 6 months. Women in the weight loss group lost an average of 8% of their body weight, compared with 1.6% in the control group. The mean loss of 8% body weight was associated with a 58% reduction in weekly SUI episodes compared with 33% for controls (P 5 .01) at 6 months. Women in either group who maintained a 5% to 10% weight loss at 18 months were more than
Stress Urinary Incontinence
twice as likely as those who gained or maintained their weight to report a 70% reduction in symptoms, which was the investigators’ a priori definition of clinically significant improvement in incontinence.9 Women in the control arm perceived a 53% decrease in frequency of incontinence episodes when measured by Likert scale following the control interventions alone, despite minimal mean weight loss. A beneficial effect of weight reduction on stress incontinence was also shown by the Action for Health in Diabetes (AHEAD) study of 2739 women with type 2 diabetes and a 13% prevalence rate of SUI.10 Women were randomized to an intensive lifestyle modification weight loss program versus diabetes support and education, resulting in average weight loss of 7.7 kg compared with 0.7 kg respectively (P 5 .01). At 1 year, women in the study group were less likely to report new SUI symptoms (3.8% vs 6.2%, P 5 .01) but no difference was seen in the rate of SUI resolution (P>.17, percentages not reported). The investigators then examined the incremental effect of weight loss on SUI symptoms. Each kilogram of weight loss was associated with a 3% decrease in the odds of experiencing weekly SUI symptoms (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99, P 5 .008). Women who lost 5% to 10% of body weight were 33% less likely to report weekly SUI symptoms compared with women who maintained or gained (OR 0.67, 95% CI 0.47–0.95, P 5 .03). Those who lost 10% or more were 41% less likely to report symptoms (OR 0.59, 95% CI 0.40–0.87, P 5 .008). Bladder Training
Bladder training is a noninvasive treatment that improves symptoms of urinary incontinence. Increased benefit is seen when training is supervised by a health care provider. Bladder training consists of voiding at regularly scheduled intervals and using urge suppression techniques between voids, with a goal of decreasing total number of voids and incontinence episodes throughout the day. This common initial strategy for treatment of UUI was evaluated by Subak and colleagues11 in an RCT of 123 women with urgency (38%), stress (24%), or mixed (37%) urinary incontinence. Women in the intervention group attended six 20-minute group instructional sessions on scheduled voiding and pelvic muscle exercises, and received individualized voiding schedules. The control group received no intervention. Women in the bladder training group reported a 50% decrease in leakage episodes on a 7-day voiding diary, compared with 15% in the controls (P 5 .001). Notably, results were not stratified by type of incontinence, limiting the ability to interpret the impact of bladder training on stress urinary leakage specifically. Goode and colleagues12 evaluated pelvic floor muscle training–based behavioral therapy in a multiarm RCT. Two-hundred women with SUI or MUI were randomly assigned to supervised behavioral training, supervised behavioral training combined with pelvic floor electrical stimulation (PFES), or to a control group of women who received a self-help booklet of behavioral training techniques. The behavioral training group had 4 biweekly visits with nurse practitioners, including biofeedback to teach correct performance of pelvic floor contractions and advance their exercise regimen. The PFES group was additionally provided a home PFES unit for use on alternating days. All patients, including the control group, were instructed to perform 3 sets of fifteen 2-second to 4-second pelvic floor muscle contractions daily, use preemptive contractions before leakage-promoting activities, and use urge suppression techniques (so-called freeze and squeeze). The primary outcome was reduction in incontinence episodes on bladder diary. Incontinence episodes were reduced by 69% with supervised behavioral training alone, 72% with the addition of PFES, and 53% for subjects who received a pelvic floor muscle exercise instruction booklet without supervision. Improvement in both the behavioral training and PFES groups were significantly
47
48
Lavelle & Zyczynski
higher compared with controls, but not different from each other (P 5 .02, P 5 .002, and P 5 .60). Pelvic Floor Muscle Therapy Versus No Treatment
Physical therapy directed at improving pelvic muscle function is a long-standing primary treatment of SUI. In 1948, Kegel13 reported improvement of incontinence symptoms in women using pelvic floor strengthening exercises. Over the subsequent half-century, instructions for pelvic muscle contractions have been supplemented with biofeedback devices, electrical stimulation, and weighted vaginal cones. PFMT as a treatment modality for SUI has been compared with both expectant and surgical management. Supervised PFMT results in improvement in SUI symptoms with low risk of adverse events. However, absolute cure rates are low. PFMT was compared with expectant management by Bø and colleagues14 in 1999. In a multiarm design, 122 women with SUI were randomized to PFMT, daily use of vaginal electrical stimulation, daily use of weighted vaginal cones, or no treatment. Patients in the PFMT arm performed 3 daily sets of 8 to 12 high-intensity contractions lasting 6 to 8 seconds. Correct use of pelvic muscles was confirmed at enrollment by a physical therapist. The primary outcomes were change from baseline in pad weight on standardized stress test, and SUI symptoms on a 5-point scale from unproblematic to very problematic. At 6 months, pad weight decreased significantly more for women in the PFMT group compared with the other 3 groups (PFMT 30.2 g vs control 12.7 g, P 5 .02; electrical stimulation 7.4 g, P 5 .02; and vaginal cones 14.7 g, P
MD
a,
*, Halina M. Zyczynski,
MD
b
KEYWORDS Stress urinary incontinence (SUI) Treatment Comparative efficacy Review KEY POINTS Weight loss of 5% to 10% of body weight results in more than 50% reduction in weekly stress urinary incontinence episodes. Approximately half of women with stress urinary incontinence experience symptom improvement from pelvic floor muscle therapy, compared with less than 10% with expectant management, and 91% after midurethral sling. Up to half of women who receive pelvic floor muscle therapy as initial treatment of moderate to severe stress urinary incontinence subsequently pursue surgical management. Surgery offered as first-line intervention is more likely to result in continence and treatment satisfaction in a shorter interval. Both retropubic and transobturator approaches to midurethral sling are highly successful procedures for stress urinary incontinence, with high long-term patient satisfaction. Adverse event profiles differ between approaches. Patients with contraindications or aversion to surgical mesh can be reassured that a Burch colposuspension or fascial pubovaginal sling result in similar continence rates and perioperative complications compared with midurethral slings.
INTRODUCTION
Almost 16% of community dwelling women in the United States report symptoms of urinary incontinence.1 Most of these women report symptoms of stress urinary incontinence (SUI), or involuntary urine loss associated with coughing, sneezing, or other physical activity, without a preceding detrusor contraction.2–4 Some women
Disclosure: The authors have nothing to disclose. a Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA; b Division of Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA * Corresponding author. E-mail address: [email protected] Obstet Gynecol Clin N Am 43 (2016) 45–57 http://dx.doi.org/10.1016/j.ogc.2015.10.009 obgyn.theclinics.com 0889-8545/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
46
Lavelle & Zyczynski
experience only stress-type incontinence, whereas many others report additional leakage symptoms such as urgency urinary incontinence (UUI), or leakage following a sudden and urgent need to void secondary to detrusor spasm. The combination of incontinence mechanisms is referred to as mixed urinary incontinence (MUI). SUI results in significant personal and financial burden for symptomatic women. Threequarters of women who experience SUI report significant bother from their symptoms, and an estimated 13.6% of American women elect to undergo surgical treatment of SUI.5 Management strategies to reduce the burden of SUI include behavioral changes, weight reduction, pelvic floor muscle therapy (PFMT), and various surgical interventions. This article reviews the highest-quality clinical trials comparing contemporary treatment options for women with SUI. When available, results from large multicenter randomized controlled trials (RCTs) are highlighted. In their absence, results from smaller and single-site RCTs are reported, acknowledging their limitations. Clinicians and patients can use this compendium of the highest-quality studies to inform their treatment selection. For each trial, the population characteristics, number of participants, intervention, primary outcome, and notable secondary outcomes are presented. Where systematic reviews or meta-analyses are available, their findings are included as well. NONSURGICAL MANAGEMENT FOR STRESS URINARY INCONTINENCE
Nonsurgical management strategies targeting SUI offer patients the potential for symptom improvement while avoiding the risk of surgical morbidity, such as perioperative complications, postoperative voiding dysfunction, or mesh exposure. The interventions in this class use behavior or lifestyle modifications such as bladder training, fluid management, and weight loss. Physical therapy targeting optimization of pelvic floor function, often referred to as PFMT, and incontinence pessaries are adjuvants to behavioral modifications. Outcomes of these strategies, used individually or in combination as first-line therapy, were investigated in several randomized trials. Fluid management, a keystone of behavior intervention for bladder symptoms, entails moderating total fluid intake and specifically bladder irritants such as caffeine and alcohol. Fluid management has not been addressed in a clinical trial for SUI treatment. Remaining treatments are addressed later. Weight Loss
Overweight and obese women who lose 5% to 10% of their body weight can expect significant improvement in SUI. Obesity is a risk factor for incontinence and imparts a 3-fold to 4-fold risk for SUI.6,7 Sustained weight reduction among obese and morbidly obese women has shown substantial improvement in their incontinence symptoms in 2 large trials. The Program to Reduce Incontinence by Diet and Exercise (PRIDE) study randomized 338 women to an intensive 6-month behavioral weight loss program versus a control treatment of 4 educational sessions on weight loss and healthy diet.8 Both groups received an instruction booklet describing pelvic floor strengthening, incontinence suppression techniques, and bladder diaries. The primary outcome was weekly episodes of SUI reported by bladder diary at 6 months. Women in the weight loss group lost an average of 8% of their body weight, compared with 1.6% in the control group. The mean loss of 8% body weight was associated with a 58% reduction in weekly SUI episodes compared with 33% for controls (P 5 .01) at 6 months. Women in either group who maintained a 5% to 10% weight loss at 18 months were more than
Stress Urinary Incontinence
twice as likely as those who gained or maintained their weight to report a 70% reduction in symptoms, which was the investigators’ a priori definition of clinically significant improvement in incontinence.9 Women in the control arm perceived a 53% decrease in frequency of incontinence episodes when measured by Likert scale following the control interventions alone, despite minimal mean weight loss. A beneficial effect of weight reduction on stress incontinence was also shown by the Action for Health in Diabetes (AHEAD) study of 2739 women with type 2 diabetes and a 13% prevalence rate of SUI.10 Women were randomized to an intensive lifestyle modification weight loss program versus diabetes support and education, resulting in average weight loss of 7.7 kg compared with 0.7 kg respectively (P 5 .01). At 1 year, women in the study group were less likely to report new SUI symptoms (3.8% vs 6.2%, P 5 .01) but no difference was seen in the rate of SUI resolution (P>.17, percentages not reported). The investigators then examined the incremental effect of weight loss on SUI symptoms. Each kilogram of weight loss was associated with a 3% decrease in the odds of experiencing weekly SUI symptoms (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99, P 5 .008). Women who lost 5% to 10% of body weight were 33% less likely to report weekly SUI symptoms compared with women who maintained or gained (OR 0.67, 95% CI 0.47–0.95, P 5 .03). Those who lost 10% or more were 41% less likely to report symptoms (OR 0.59, 95% CI 0.40–0.87, P 5 .008). Bladder Training
Bladder training is a noninvasive treatment that improves symptoms of urinary incontinence. Increased benefit is seen when training is supervised by a health care provider. Bladder training consists of voiding at regularly scheduled intervals and using urge suppression techniques between voids, with a goal of decreasing total number of voids and incontinence episodes throughout the day. This common initial strategy for treatment of UUI was evaluated by Subak and colleagues11 in an RCT of 123 women with urgency (38%), stress (24%), or mixed (37%) urinary incontinence. Women in the intervention group attended six 20-minute group instructional sessions on scheduled voiding and pelvic muscle exercises, and received individualized voiding schedules. The control group received no intervention. Women in the bladder training group reported a 50% decrease in leakage episodes on a 7-day voiding diary, compared with 15% in the controls (P 5 .001). Notably, results were not stratified by type of incontinence, limiting the ability to interpret the impact of bladder training on stress urinary leakage specifically. Goode and colleagues12 evaluated pelvic floor muscle training–based behavioral therapy in a multiarm RCT. Two-hundred women with SUI or MUI were randomly assigned to supervised behavioral training, supervised behavioral training combined with pelvic floor electrical stimulation (PFES), or to a control group of women who received a self-help booklet of behavioral training techniques. The behavioral training group had 4 biweekly visits with nurse practitioners, including biofeedback to teach correct performance of pelvic floor contractions and advance their exercise regimen. The PFES group was additionally provided a home PFES unit for use on alternating days. All patients, including the control group, were instructed to perform 3 sets of fifteen 2-second to 4-second pelvic floor muscle contractions daily, use preemptive contractions before leakage-promoting activities, and use urge suppression techniques (so-called freeze and squeeze). The primary outcome was reduction in incontinence episodes on bladder diary. Incontinence episodes were reduced by 69% with supervised behavioral training alone, 72% with the addition of PFES, and 53% for subjects who received a pelvic floor muscle exercise instruction booklet without supervision. Improvement in both the behavioral training and PFES groups were significantly
47
48
Lavelle & Zyczynski
higher compared with controls, but not different from each other (P 5 .02, P 5 .002, and P 5 .60). Pelvic Floor Muscle Therapy Versus No Treatment
Physical therapy directed at improving pelvic muscle function is a long-standing primary treatment of SUI. In 1948, Kegel13 reported improvement of incontinence symptoms in women using pelvic floor strengthening exercises. Over the subsequent half-century, instructions for pelvic muscle contractions have been supplemented with biofeedback devices, electrical stimulation, and weighted vaginal cones. PFMT as a treatment modality for SUI has been compared with both expectant and surgical management. Supervised PFMT results in improvement in SUI symptoms with low risk of adverse events. However, absolute cure rates are low. PFMT was compared with expectant management by Bø and colleagues14 in 1999. In a multiarm design, 122 women with SUI were randomized to PFMT, daily use of vaginal electrical stimulation, daily use of weighted vaginal cones, or no treatment. Patients in the PFMT arm performed 3 daily sets of 8 to 12 high-intensity contractions lasting 6 to 8 seconds. Correct use of pelvic muscles was confirmed at enrollment by a physical therapist. The primary outcomes were change from baseline in pad weight on standardized stress test, and SUI symptoms on a 5-point scale from unproblematic to very problematic. At 6 months, pad weight decreased significantly more for women in the PFMT group compared with the other 3 groups (PFMT 30.2 g vs control 12.7 g, P 5 .02; electrical stimulation 7.4 g, P 5 .02; and vaginal cones 14.7 g, P
