Stress urinary incontinence: An undertreated problem which deserves attention

Journal Pre-proof Stress urinary incontinence: an under-treated problem which deserves attention Jeanne S. Chow, MD, Associate Professor PII:

S2468-4511(19)30055-8

DOI:

https://doi.org/10.1016/j.cobme.2019.10.006

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COBME 188

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Current Opinion in Biomedical Engineering

Received Date: 3 October 2019 Accepted Date: 4 October 2019

Please cite this article as: J.S. Chow, Stress urinary incontinence: an under-treated problem which deserves attention, Current Opinion in Biomedical Engineering, https://doi.org/10.1016/ j.cobme.2019.10.006. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.

Stress urinary incontinence: an under-treated problem which deserves attention

Jeanne S. Chow, MD [email protected] Associate Professor, Harvard Medical School Boston Children’s Hospital 300 Longwood Avenue Boston MA, 02115 Highlights: -Stress urinary incontinence (SUI) affects nearly 50% of adult women -SUI is under-reported -Treatments for SUI currently exist, but they are underutilized

Key words: urinary tract, stress urinary incontinence, incontinence, biofeedback, pelvic floor muscle training, sling surgery

Abstract Stress urinary incontinence is the involuntary leakage of urine with occurs with sudden increases in abdominal pressure, such as during sneezing, coughing or laughing. This is a common symptom in women, affecting greater than 50% of women and a cause of substantial morbidity. Women and men do not commonly report this symptom to their physicians. This under-reporting may be one of the reasons for under-treatment. In fact, successful treatments exist which decrease or cure stress urinary incontinence, including pelvic floor muscle training and various surgeries but only a small fraction of those with SUI receive treatment.

Stress urinary incontinence: an under-treated problem which deserves attention Abbreviations: Urinary incontinence (UI) Stress urinary incontinence (SUI) Urgency urinary incontinence (UUI) American Urological Association (AUA) Internal urethral sphincter (IUS)

Body Mass Index (BMI) Electromyography (EMG) Mixed urinary incontinence (MUI) Pelvic floor muscle training (PFMT) External urethral sphincter (EUS)

1. Introduction Stress urinary incontinence (SUI), the involuntary leakage of urine due to increased abdominal pressure, is a common, under-reported embarrassing symptom which is a significant cause of decreased quality of life and economic burden [1]. The main cause of SUI is pelvic floor laxity and muscle weakness. Although both pelvic floor muscle training (PFMT) and surgery are successful in treating incontinence only a small proportion of those with incontinence get treatment. Instead, most people with SUI are managing their symptoms with incontinence pads or adult diapers. The adult diaper industry is the fastest growing paper industry, and is expected to surpass the infant diaper market in the next ten years [2]. The treatable symptom of SUI is masked and remains largely untreated. Under-treatment is due to a variety of factors including underreporting. It takes an average of 6.5 years of incontinence before a woman seeks medical help [3]. Delayed reporting is due to embarrassment, assumption that SUI is normal part of life related to aging and childbirth and lack of education that treatments are available. These concepts result in women being unlikely to consult their physician or other healthcare practitioners [4]. Men are half as likely to seek help compared to women ; 1 in 5 men with symptoms seek medical care [5][6]. Even when healthcare providers are consulted, there are surprisingly low rates of treatment of women with leakage symptoms [7][8]. The “cost” of urinary incontinence to the individual is difficult to measure and depends on gender, age, and degree of incontinence but is known to have a significant negative impact on the quality of life for the patient, family and friends [9][10][11]. Those with incontinence experience discomfort, low selfesteem, mood deterioration and the feeling of helplessness. There is a decline in the quality of their personal, social and professional life. People fear others discovering their condition, and that forces changes in lifestyle which contributes to social isolation and alienation [12][13][14][15]. It has been estimated that the total annual direct and indirect cost of urinary incontinence in the United States was 19.5 billion in 2004 [16] and presumed much greater in 2019. This article describes the pathophysiology and current treatments of stress urinary incontinence. The purpose of writing this article is to increase awareness of this common medical problem in the hope of improving treatment. 2. The pathophysiology of continence Urinary continence is maintained when the pressure of the urethral sphincter, the muscle which maintains continence, is greater than the bladder pressure. The urethral sphincter is composed of smooth muscle extending from the bladder neck (internal urethral sphincter (IUS)) and striated circular

and longitudinal muscle (external urethral sphincter (EUS)). The smooth muscle is under involuntary control. The striated muscle is under voluntary control. In men, the prostate gland surrounds the urethral sphincter and reinforces the continence mechanism. In females, the vaginal wall and connective tissue between the vagina and urethra form part of the continence mechanism. The urethral sphincter and bladder base are supported by the pelvic sling, a hammock-like structure which is composed of the levator ani muscles and tendons, connective tissues to the bones, and the anterior vaginal wall in females. When there is increased intra-abdominal pressure, such as due to coughing or sneezing, the levator ani muscles contract to keep the pressure higher in the urethra than bladder and maintain continence [17]. Since both smooth and striated muscles are involved in continence, both autonomic nervous system defects and peripheral nerve damage can contribute to incontinence. For example, damage to the pudendal nerve, the nerve controlling the EUS, such as during surgery or child bearing can lead to incontinence. Urinary incontinence (UI) occurs when the pressure in the bladder exceeds that of the urethral sphincter. Stress urinary incontinence (SUI) occurs when there is sudden increase in intra-abdominal pressure, such as during sneezing, coughing, exercise, lifting and position change. This is distinguished from urgency urinary incontinence (UUI), where the symptom occurs in conjunction with the sudden desire to urinate which cannot be deferred. Mixed urinary incontinence (MUI) refers to the combination of SUI and UUI [18]. Approximately 88% of all incontinent patients have stress incontinence [19]. 3. Who is affected? Urinary incontinence affects over 420 million people world-wide. These numbers are likely underestimates because a majority of sufferers fail to report UI to their health-care providers [20][21]. Depending on the population, as few as 14% of women [22][23][24][25][26] [27] report this symptom to their physician. Due to the absence of the prostate gland and the injuries leading to weakness of the pelvic sling during childbearing, childbirth and aging, women are much more likely to suffer from stress urinary incontinence than men. 70% of patients with SUI are women. According to the American Urological Society, SUI affects nearly 50% of adult women [28]. The population with incontinence has been steadily growing over the past decade due to the aging population [29]. The prevalence of UI increases with age. Moderate to severe UI affects 7% of women 20–39 years of age, 17% 40–59 years of age, 23% 60–79 years of age, and 32% ≥80 years of age [30]. The most common cause of SUI in men is radical prostatectomy. The external urethral sphincter is damaged during surgical dissection because the prostate partially surrounds the sphincter. SUI is often temporary and resolves within the first post-operative year [31] however upto 40% of men report some long-term urinary incontinence, most of which are described as mild symptoms [32]. Obesity is a cause of stress urinary incontinence due to increased intra-abominal pressure leading to increased intravesical pressure [33]. For each 5-unit increase in body mass index (BMI), there is a 10% increased odds of SUI [34], so that among women with a BMI ≥ 40 kg/m2, the prevalence of SUI is nearly 70% [35]. Less common causes of incontinence, not further discussed in this paper, are neurogenic causes due to central or peripheral nerve defects or damage .

4. Treatment: What are the current available treatments for stress urinary incontinence? Most women manage their incontinence by accepting it as a fact of life, a natural result of child-bearing and age, and use an absorbable undergarment (pad or diaper) to manage their symptoms. In addition, adults limit their physical activity, avoid embarrassing situations, and this leads to decreased social activity and isolation. For those who try to treat rather than manage their symptoms, strategies to prevent incontinence keep the balance of sphincter pressure greater than bladder pressure and range from non-invasive methods including life-style changes to physical therapy to surgery. If the patient seeks treatment from a physician, the following are the recommended therapies from the American Urological Association: observation, pelvic floor muscle training (PFMT), other non-surgical options such as a pessary, and surgical intervention [28]. There are no FDA-approved medications for stress urinary incontinence [36]. 4.1. The first treatment is life-style modification. This often begins before seeking professional advice. Decreasing fluid intake and limiting diuretics such as caffeinated beverages and alcoholic beverages, prevent the bladder from (over)filling. Many patients also limit physical activity to decrease the frequency of “accidents” and avoid social situations to avoid embarrassment [37]. There is stong evidence that weight loss decreases incontinence for overweight individuals. For obese women who are able to lose 5-10% of their weight, 70% experience reduction in their SUI incidents [38]. 4.2 Physical therapy which trains the bladder and pelvic floor muscles is the first line of treatment prescribed by physicians and physical therapists. Bladder training is a form of timed voiding which is a form of behavioral therapy in which the bladder is slowly “trained” to hold greater quantities of urine by incrementally increasing the time between voiding. Pelvic floor muscle training (PFMT) is physical therapy training used to strengthen the pelvic floor muscles. The American gynecologist Arnold Kegel popularized his Kegel exercises after showing that the systematic exercise of the pelvic floors strengthens and increases coordination of muscles compared to inactivity and leads to better urethral compression and decreased incontinence [39]. Systematic reviews consistently report the efficacy of PFMT [40][41][42][43][44][45]. Exercises increase the bulk of the muscular tissue ,reduces bladder neck mobility during cough and increases the cross- sectional area of the urethra, due to muscular hypertrophy [46]. PFMT results in reductions of up to 80% in the frequency of incontinence episodes [47][48] and cure rates in as many as 50% of women [49]. As Kegels decrease UI, quality of life improves [50]. PFMT success is dependent on the patient understanding how to isolate his or her pelvic floor muscles, a group of muscles which cannot be seen directly, through biofeedback. Thus the most successful PFMT is performed in physicians and physical therapists offices, where the contractions of the pelvic floor

muscles can be isolated for the patient, and measured using electromyography (EMG) with probes placed inside the rectum or vagina. In children, EMG measurements are made at the skin surface. Portable physical therapy devices exist, specifically for vaginal insertion in women, and include cones, weights, or electronic devices. Weighted cones and similar devices are held tightly in the vagina through contraction of the pelvic floor muscles to prevent them from slipping out. Electronic devices using Apps, provide training exercises and biofeedback and measure the strength of contractions electronically. These devices allow for PFMT to occur outside of the hospital and physical therapy clinics. Selfrehabilitation in additional to conventional PFMT improves the strengthening of the pelvic floor muscles [51]. Use of cones are better than no treatment with SUI and may be of similar effectiveness as PFMT [44]. PFMT improves post-surgical urinary incontinence in patients after prostatectomy [52][53]. Electrical stimulation using vaginal and anal probes of the nerves of incontinence can be performed independently or as an adjunct to PFMT [54]. A Cochrane database systematic review concludes that the overall quality of the studies proving the efficacy of electrical stimulation is poor and that electrical stimulation is probably more effective than no treatment, but it is difficult to compare effectiveness compared to PFMT [55]. Small studies have shown that intravaginal electrical stimulation is as successful as Kegel exercises for urinary incontinence [56] and have shown improvement in upto 66% patients [56][57]. 4.3 Medications Although there are no FDA-approved medications for stress urinary incontinence, some medications used for urgency incontinence are used as a second-line treatment [58][59] for SUI. Alpha-agonists increase the contraction of the internal urethral sphincter thus increasing urethral resistance. However the level of evidence supporting its use for SUI is low due to the lack of randomization of studies[60]. Duloxetine, a dual serotonin and norepinephrine reuptake inhibitor, was liscenced and approved in Europe as an add-on therapy for SUI. However, licensing in the US and Canada failed due to concerns over increased risk for suicide [61]. Anticholinergic medications inhibit the binding of acetylcholine to the cholinergic receptor, suppressing involuntary bladder contraction, and thus is a treatment of urge urinary incontinence rather than stress urinary incontinence. The decreasing levels of estrogen have been attributed to cause of urinary incontinence in postmenopausal women and thus estrogen replacement therapy was considered a therapy to reduce urinary incontinence. However, systemic estrogen has been shown to worsen the symptoms of SUI and topical estrogen is only provides minimal improvement [59][62]. 4.4 Surgical interventions Surgical interventions are considered for patients who have severe limitation of activity. These aim at creating additional pressure at the level of the bladder neck and urinary sphincter. The success of surgery for incontinence increases with post- operative PFMT [63]. There is an estimated 200,000 women undergo repair annually. The rates are predicted to increase in the coming years secondary to an aging population [64]. The following are the interventions recommended by the American Urological Association (AUA) [28].

Pessary and vaginal inserts are devices which prevent incontinence by supporting the pelvic organs. Pessaries are typically made of silicone. Inserts have the appearance of a tampon, but once inserted, support and lift the urethra to prevent leakage. Mid urethral sling is a synthetic strap, typically created from polypropylene, that is surgically placed to support the urethra and base of the bladder like a hammock. The retropubic and transobturator surgical approaches place the sling from the anterior retropubic approach and perineal approach respectively and fasten the ends of the slings around the pubic bone anteriorly or between the two obturator foramens posteriorly [65]. Alternatively, fascial tissue from the abdomen or thigh can be used to create a sling, called autologous fascia pubovaginal sling. Slings have a good safety profile and highly effective in the short and medium term for improving incontinence [66]. The procedure in males is slightly different than females [31]. Burch colposuspension is a surgery for incontinence in females in which the urethra and bladder base are secured to paravaginal tissues . This surgery has a high success rate for curing incontinence, at 8590% at one year and 70% at 5 years [67]. Bulking agents injected in the submucosal space around the urethra restores normal mucosal coaptation and increases urethral resistance [68]. This is a less invasive procedure than the previously described surgeries. However, the ideal bulking agent which would be easily injectable, cost-effective, biocompatiable and stable in the injected position does not currently exist and the efficacy of this method is modest at best with data currently insufficient to guide practice [69][70]. Injecting muscle derived stem cells into the urethral sphincter is a theoretically promising method to treat incontinence. The injected stem cells regenerate and differentiate in to the local myogenic cells to repair the damaged sphincter [71][72][73][74]([75][76] and in small series have shown clinical improvement [77]. Currently, stem cell therapy is not recommended for stress urinary incontinence outside of investigative protocols [28]. 5. Summary Stress urinary incontinence, the leakage of urine due to sudden increase in intra-abdominal pressure, is a common symptom that effects 50% of women and men after radical prostatectomy. This symptom is currently under-treated, partially because people do not report their symptoms, and never get access to a treatments which can solve their symtoms through pelvic floor muscle training or surgery. By increasing awareness to the problem of SUI and current solutions, hopefully more of those who suffer can be treated and new treatments can be developed. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgement I thank Rhonda Johnson for her tireless support of this and so many projects.

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