Treatment options for female urinary incontinence

Med Clin N Am 88 (2004) 345–366

Treatment options for female urinary incontinence Suzette E. Sutherland, MDa,b, Howard B. Goldman, MDa,* a

Department of Urology, Case School of Medicine, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106, USA b Metropolitan Urologic Specialists, PA, 2550 University Avenue West, #240N, St. Paul, MN, 55114, USA

Urinary incontinence is one of the most common diseases in women, with a prevalence of 12% to 55% across all age groups. Compared with other common chronic diseases in this population, the prevalence of incontinence is higher than that of hypertension, depression, and diabetes mellitus (Fig. 1) [1–5]. The fear and stress of coping with the embarrassment of urinary incontinence and the resulting restrictions to daily activities can significantly impact quality of life [6]. But beyond just quality of life, real physical morbidity can occur. A recent study of over 6000 community-dwelling women identified urinary incontinence as an independent risk factor for falls and fall-related fractures [7]. The sensation of urgency associated with an overactive bladder (OAB), necessitating multiple urgent trips to the bathroom, increased the risk of falls and fractures by 26% and 34%, respectively. The overall economic burden of urinary incontinence is greater than $26 billion annually, with the routine care and consequences associated with incontinence making up well over 50% of these costs (ie, pads and diapers, laundry costs, urinary tract and skin infections) [8]. Appropriately treating these patients should significantly improve their quality of life and reduce overall economic expenditures. The first step toward appropriate treatment is making the correct diagnosis. There are several distinct types of urinary incontinence (Table 1), and the treatments vary depending on the types. A brief review follows.

* Corresponding author. E-mail address: [email protected] (H.B. Goldman). 0025-7125/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/S0025-7125(03)00146-9

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Fig. 1. Incontinence and other chronic diseases in women. (From Kreder KJ. Managing incontinence: one size does not fit all. Contemp Urol 2002;14(Suppl 9):S5; with permission.)

Urge incontinence Urge incontinence (UI), or the sudden, uncontrollable urge to void followed by urinary leakage, is one of a number of types of irritative bladder symptoms collectively called the OAB. According to the new nomenclature developed by the International Continence Society, the syndrome of overactive bladder is defined as ‘‘urgency, with or without urge incontinence, usually with frequency and nocturia . . . if there is no proven

Table 1 Types of incontinence Type

Description

Urge or overactive bladder Stress

Involuntary bladder contractions or hypersensitivity

Mixed Overflow Functional Transient Continuous or postvoid

Leakage following increases in abdominal pressure (Valsalva’s maneuver) caused by urethral hypermobility or poor urethral coaptation Urge and stress components combined Bladder overdistention caused by bladder outlet obstruction (anatomic or functional) or poor detrusor contraction Physical or cognitive impairments interfering with the ability to void at socially appropriate times Acute illness or medications influencing urine volume or urinary tract function Associated with anatomic defects (urethral diverticulum, vesicovaginal fistula, etc)

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infection or other obvious pathology’’ [9]. Patients with this type of urgerelated incontinence generally experience the loss of large amounts of urine with each incontinent episode [10]. The overactive or hypersensitive bladder may contract spontaneously, or may be provoked easily by relatively low urine volumes, rapid filling, or changes in position or physical activity. The prevalence of OAB is 40% to 70% of all urinary incontinence, and is seen more commonly in women over the age of 60 [11].

Stress incontinence Stress urinary incontinence (SUI) is defined as leakage of urine, usually a small-to-moderate amount, which is triggered by activities that result in an increase in abdominal pressure (coughing, sneezing, straining, and exercise). Specifically, intra-abdominal pressure rises above the pressure provided by urethral resistance, thereby resulting in loss of urine. A structural or anatomic defect in the pelvic floor leading to urethral hypermobility, together with some element of failed coaptation of the urethral mucosal wall, is the most common cause of SUI. When loss of mucosal coaptation is the predominant element, the leakage is usually more severe. A number of risk factors have been identified for the development of SUI (Fig. 2) [5].

Fig. 2. Risk factors for stress urinary incontinence in women. (From Bump RC, Norton PA. Epidemiology and natural history of pelvic floor dysfunction. Obstet Gyn Clin N Am 1998;25(4):723–46; with permission.)

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Vaginal delivery It has been well established that childbearing is a risk factor for urinary incontinence among young and middle-aged women. Irreversible trauma to the supportive pelvic muscles and nerves can result from excessive mechanical pressure, stretching, and shearing forces during passage of the infant through the vaginal canal [12]. The neuromuscular effects can be more pronounced with larger infants and a prolonged or protracted second stage of labor. Likewise, instrumentation (forceps or vacuum) or episiotomy can further increase the risk of pelvic floor dysfunction and incontinence [13,14]. Women who develop SUI in the immediate postpartum setting usually regain full control within 3 to 6 months [15]. The risk of persistent incontinence following a first delivery, however, has been noted to be as high as 30% at 5 years [16]. With additional pregnancies, pelvic floor and bladder dysfunction may become more severe, making it less likely that complete continence is restored. Pregnancy Although vaginal delivery is thought to be the main contributing factor for the development of SUI, the mechanical and hormonal changes associated with pregnancy itself pose a significant risk to the pelvic floor. Half of all women pregnant for the first time experience some degree of SUI, especially during the final trimester. In a recent study comparing mode of delivery, the risk of urinary incontinence was highest among vaginal deliveries (21%), but was likewise significantly higher among cesarean section deliveries (15.9%) when compared with nulliparous women (10.1%) [17]. Furthermore, the age-adjusted odds ratios for incontinence for women who underwent cesarean section or vaginal delivery were 1.5 and 2.3, again compared with nulliparous women. Although there was a significant association between SUI and mode of delivery, a similar association was not seen with urge incontinence. Significantly more mixed-type incontinence was seen in the cesarean section group, suggesting that childbearing is associated with an increased risk of both SUI and mixed-type incontinence, whereas mode of delivery only influences the risk of SUI. Some suggest that the protective benefit of cesarean delivery on the development of pelvic floor dysfunction is maximized when it is performed on an elective basis before the onset of labor [18]. Prior pelvic surgery (hysterectomy, other) Prior hysterectomy has been associated with a 40% risk of future incontinence [19]. Likewise, radical pelvic surgery, vaginal surgery, pelvicperineal trauma, or radiation all disrupt the neuromuscular integrity of the pelvis. Pelvic muscle weakness leads to prolapse of the pelvic organs (cystocele, uterine, or vaginal vault prolapse), which can increase the risk of bladder dysfunction and incontinence.

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Obesity Numerous studies have identified obesity as a risk factor for SUI. The additional weight results in higher pressures on the bladder, and causes greater mobility, or hypermobility, of the urethra. Another hypothesis relates to pressure-induced pelvic nerve and vascular impairment to the bladder [20–22]. Smoking and lung disease The increased intra-abdominal pressures associated with the frequent, harsh cough often seen with smoking or lung disease have been shown to promote the development of SUI [23]. The increased intra-abdominal pressures cause repeated strain on the pelvic support structures. It has also been suggested that nicotine increases the risk of urgency and urge incontinence by acting as a direct irritant to the bladder wall, thereby inducing spontaneous detrusor contractions. Menopause The estrogen depletion associated with menopause results in atrophy of the mucosal lining of the urethra. Similarly, atrophy of the vaginal mucosa can be seen, which may serve as a marker for urethral atrophy. This mucosal deficiency can result in difficulties with urethral coaptation, predisposing the woman to urinary leakage. In addition, the support provided by the pelvic musculature weakens more rapidly in the postmenopausal woman, leading to pelvic organ prolapse and, in some, urinary incontinence. Physical activity Physical activities associated with increased abdominal pressure or highimpact jarring forces on the trunk can decrease the supporting strength of the pelvic floor. Such activities include gymnastics, jumping, running, horseback riding, martial arts, and heavy weight lifting. It has been suggested that at least 50% of women who maintain a regular exercise regimen involving high-impact activities develop some degree of SUI [24]. Low-risk activities include swimming, bicycling, walking, and rowing. Age Changes within the lower urinary tract occur with age, even in the absence of disease. The incidence of SUI in women increases with age and is commonly believed to be related to the inherent age-related weakness of the supportive fascial tissues, ligaments, and muscles of the pelvic floor. Dementia and debility Urinary incontinence is more common in demented than nondemented elderly, with nearly 30% of frail demented individuals suffering from SUI.

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Incontinence in demented individuals, however, is usually multifactorial, with treatable underlying causes [25]. Functional or mobility status has the greatest effect on urinary control in the elderly, especially in those who are severely demented.

Mixed-type incontinence Mixed incontinence includes symptoms of both OAB-urge incontinence and SUI. As many as 50% to 60% of patients presenting for evaluation of SUI also have some symptoms of OAB-urge incontinence. Proper management of mixed-type incontinence requires recognizing, evaluating, and treating each component.

Overflow incontinence Overflow incontinence occurs when the bladder is chronically full and distended. This may occur from either an obstructive phenomenon at the level of the bladder outlet (ie, urethral kinking secondary to pelvic organ prolapse, iatrogenic obstruction following an anti-incontinence surgery, and so forth), or from a functional phenomenon associated with the loss of the bladder’s ability to contract. In either case, emptying the bladder is difficult, leading to chronic distention, bladder irritability, and urinary leakage. It is imperative that problems with bladder emptying such as these be diagnosed promptly by postvoid residual assessment, because chronic hydronephrosis may result and eventually lead to irreversible impairment in renal function.

Functional incontinence A variety of physical or cognitive impairments can interfere with independent activities of daily living. Most commonly, conditions associated with mobility restrictions, such as arthritis, orthopedic deformities, paralysis, muscular atrophy, and the use of bed restraints, can lead to urinary incontinence. Likewise, impaired vision, disequilibrium, fear of falling, and confusion or dementia can limit mobility.

Transient incontinence Transient incontinence occurs in up to 35% of community-dwelling elderly and up to 50% of acutely hospitalized patients [26]. The mnemonic DIAPPERS (Box 1) is used to describe the various etiologies of incontinence that are transient in nature. The underlying problem contributing to incontinence must be identified and treated before other

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Box 1. Transient incontinence D elirium or confused state Infections, urinary (symptomatic) A trophic urethritis or vaginitis P harmaceuticals P sychologic factors (depression, psychosis) E xcessive urine output (CHF, DM) R estricted mobility S tool impaction or constipation

appropriate bladder management options can be considered. Frequently, treatment of the transient factor may be all that is required to achieve continence. Delirium or cognitive impairment can predispose one to urinary incontinence, especially urge and functional incontinence. The cause of the decreased mentation must be addressed (hypoxemia, electrolyte disorder, pharmaceuticals) before considering treatment options for incontinence. With transient delirium, the associated symptoms should abate following resolution of the delirium. As a bladder irritant, infections and inflammation of the urinary tract induce spontaneous detrusor contractions, manifesting as a sense of urgency and, often, urge incontinence. Likewise, the inflammation and perineal discomfort associated with atrophic urethritis or vaginitis can induce or worsen irritative voiding symptoms and urge incontinence, and SUI. Initial treatment involves estrogen replacement. Medications (pharmaceuticals) are the most common cause of transient urinary incontinency [27]. Pharmacologic agents can play a multifactorial role on continence. Their side effects must be considered because they relate to the patient’s mobility, mentation, and urinary tract function (Table 2). Psychologic factors can also affect aspects of daily function. The incidence of depression among incontinent women is three times higher than in continent women. Likewise, over 60% of women with SUI complain of depressive symptoms [28,29]. Treatment of such psychologic problems can improve or abate symptoms of urinary incontinence. Similarly, treatment of urinary incontinence may help to alleviate depressive symptoms. Excessive urine output can directly lead to urinary urgency and frequency, thereby exacerbating problems with incontinence. Patients should be screened for excessive fluid intake (by a fluid-voiding diary); metabolic abnormalities (diabetes mellitus); and conditions that affect fluid regulation and balance (congestive heart failure, diabetes insipidus). Again, restricted mobility limits access to the bathroom, thereby predisposing one to urinary difficulties. Lastly, poor bowel habits leading to constipation and stool impaction are reportedly responsible for at least 10% of

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Table 2 Transient incontinence: Medicinal Causes Mechanism of incontinence

Medications

SUI: sphincter relaxation SUI: excessive coughing Overflow incontinence: decreased bladder contraction

a-Blockers ACE inhibitors Caþ–channel blockers Anticholinergics Antidepressants Sedatives-hypnotics, antipsychotics Antihistamines Central nervous system depressants Narcotics, alcohol a-Agonists b-Antagonists (blockers) Caffeine, nicotine, cholinergics Diuretics (especially loop) Sedatives-hypnotics, antipsychotics, narcotics, alcohol

Overflow incontinence: increased sphincter contraction Urge incontinence: irritants Urge incontinence: high urine flow Urge incontinence: depressed central nervous system

urinary incontinence in the elderly, and incomplete bladder emptying, urinary retention, and increased risk of urinary tract infection. Correction of abnormal bowel function often restores normal urinary function and continence.

Continuous and postvoid incontinence Leakage described as postvoid or continuous dribbling should raise the suspicion for an anatomic defect, such as a urethral diverticulum or urinary fistula (vesicovaginal, urethrovaginal, ureterovaginal). Most commonly, a fistula to the urinary system occurs after gynecologic or pelvic surgery. Continuous dribbling and a prior history of such surgery should heighten the suspicion for a fistula. This type of incontinence requires further evaluation by an urologist or urogynecologist.

Evaluation With an understanding of the common types of urinary incontinence, an appropriate evaluation can be performed. A thorough medical and symptom-related history, physical examination, and urinalysis are generally all that is required to successfully evaluate women with urinary incontinence (Table 3). More sophisticated genitourinary evaluation is usually not necessary. Abnormalities encountered on examination, however, may prompt referral to a specialist for further testing, diagnosis, and treatment. The evaluation begins with specific questions as to the nature of the urinary symptoms (urgency, frequency, onset, duration, timing, nocturia,

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Table 3 Evaluation of female incontinence Medical history Symptoms associated with incontinence

Past medical history

Past surgical history

Obstetric history

Social history Medications Physical examination Focused neurologic examination Abdominal examination Pelvic examination

Examination procedures Q-tip test PVR (postvoid residual) Provocative stress test Office cystometrics or urodynamics Laboratories Urinalysis Urine culture

Leakage with Valsalva’s maneuver (cough, sneeze, exercise) Frequency ([8 voids/d) Urgency Leakage with urgency Nocturia, enuresis Timing of leakage Awareness of leakage Severity/pad use/number Pelvic trauma Pelvic radiation Neurologic conditions Hysterectomy, prolapse repair, prior incontinence surgery Other pelvic or vaginal surgery Number of vaginal deliveries Difficult or prolonged labor Assisted delivery (ie forceps, vacuum) Smoking ETOH See table: medicinal causes Gait Perineal sensation Palpable bladder External genitalia, vaginal mucosa (atrophy, inflammation, irritation) Pelvic prolapse (eg, cystocele) Urethral palpation (masses, tender, discharge) Urethral hypermobility > 30
angle Normal \ 50 mL Visible leakage of urine with forcible straining or coughing Done by urologist or urogynecologist

If urinalysis positive for nitrites, leukocyte esterase, white blood cells, bacteria

stress-induced). The severity can be assessed by quantifying daily pad use (number or type). A 3-day voiding diary is an easy and reliable way to gain information about voiding habits (frequency, volumes per void) and the volume of fluid consumed or the intake of potential bladder irritants, such as caffeine or alcohol. Also available is the Urogenital Distress Inventory, which assesses the presence and degree of lower urinary tract symptoms in women, including incontinence [30].

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An investigation into possible transient or reversible conditions, which may influence or inhibit urinary control, must be included. Again, the mnemonic DIAPPERS is a useful tool to ensure all possible causes have been considered. A close inspection of the patient’s medication list may reveal the underlying culprit, especially in the elderly. A number of comorbidities or concomitant diagnoses can also contribute to urinary incontinence, so a thorough history and physical is imperative. An important step in determining the possible etiology of urinary leakage is to rule out overflow incontinence caused by inadequate bladder emptying and overdistention of the bladder. This can be evaluated easily by checking the postvoid residual urine volume, or the urine remaining in the bladder following voiding. Catheterization or bladder ultrasound should be performed within 15 minutes of voiding. A normal postvoid residual urine volume should be less than 50 mL; greater than 200 mL should elicit a referral to a specialist [1]. The primary problem may be a structural or functional abnormality causing urinary obstruction at the level of the bladder outlet. A weak or ineffective detrusor muscle may render it functionally impaired, thereby leading to large residual urine volumes after voiding. Although much less common in women than men, it may be important to rule out overflow incontinence before initiating treatment. Some medical options used for the treatment of urgency, frequency, and urge incontinence can worsen the bladder’s ability to empty, and thereby lead to secondary problems of urinary retention, infection, and upper urinary tract impairment. Patients at risk for urinary retention and overflow incontinence include women with severe pelvic organ prolapse (grade 3 to 4 cystocele); patients with neurologic disorders affecting spinal segments between C2 and S2; and patients with a prior history of urinary retention. An attempt to distinguish between SUI and UI should be made, because the treatment options for these two types of incontinence are different. Again, a thorough history of urinary symptoms generally allows one to make this distinction (Table 4). SUI usually results in small-to-moderate amounts of urinary leakage following activities that elicit increases in intra-abdominal pressure (coughing, sneezing, lifting, jumping, straining). Urinary incontinence from an overactive bladder is usually associated with a sudden, uncontrollable urge to void, and may likewise be associated with urinary

Table 4 Distinguishing SUI from UI Description

SUI

UI

Leakage with maneuvers that increase intra-abdominal pressure (cough, sneeze, lift, exercise) Leakage with sudden urge to void Amount of leakage per episode

+



 Small/moderate

+ Moderate/large

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frequency (more than eight voids per day). These symptoms can overlap, however, making the distinction between these two types of incontinence difficult. Many patients have significant symptoms of both SUI and UI (mixed incontinence). In these cases, it is important to distinguish which symptom is the most bothersome to the patient, and target the initial therapy accordingly, to optimize outcomes and patient satisfaction. It is also important for the primary care physician to be able to identify special or complicated situations, which warrant a referral to a urologist or urogynecologist for more advanced evaluation and treatment, listed as follows: Failure of initial conservative treatments Significant SUI Recurrent urinary tract infections Hematuria (gross or microscopic) Recent onset of OAB (few months) Significant pelvic prolapse Prior incontinence surgery Prior radical pelvic surgery Prior pelvic radiation Complicated cases include patients who have failed initial conservative treatment. Prior pelvic surgery, radiation therapy, or major pelvic prolapse often result in anatomic and functional changes of the bladder, urethra, or urinary sphincter, which require investigation by more sophisticated means (cystoscopy, cystometry, urodynamic studies). An obstetric history including prolonged vaginal deliveries or perineal trauma can uncover a structural or anatomical etiology of incontinence. Neurologic conditions, such as multiple sclerosis, diabetic neuropathy, spinal cord injuries, or lumbar disk disease, can produce a variety of complicated voiding patterns and incontinence [27,31]. Hematuria (gross or microscopic) or the recent onset of irritative voiding symptoms (urinary urgency, frequency, urge incontinence) frequently requires cystoscopic evaluation to rule out the presence of foreign bodies, stones, or tumors within the bladder. Other radiographic tests (intravenous pyelogram, renal-bladder ultrasound, CT scan, MRI) are occasionally required.

Treatment Urge incontinence First-line treatment of urge incontinence involves nonpharmacologic behavior modification strategies [32,33]. Dietary manipulations that influence the timing and volume of fluid consumption and the avoidance of potential bladder irritants are advised. With good health-conscious intentions, some women consume large quantities of fluid throughout the

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day, resulting in polyuria and exacerbation of urinary frequency and urgency. Others limit their fluid intake to reduce these bladder symptoms. Unfortunately, relative dehydration leads to concentrated urine within the bladder, which can itself serve as an urge-producing irritant. Patients should avoid extremes in fluid consumption and adhere to a recommended daily fluid allowance of approximately 30 mL/kg of body weight (0.5 oz/lb). Although there are a number of dietary substances identified as potential bladder irritants, only two have been rigorously confirmed through scientific means: caffeine and alcohol [34,35]. The stimulatory effect of caffeine has been shown to directly influence the detrusor muscle. The suppressive effects of alcohol are seen on both vasopressin (antidiuretic hormone) and the central nervous system, resulting in a diuresis combined with an inhibition of cognitive bladder sensation. A recent multivariate analysis established causal associations with obesity, smoking, and carbonated beverages for the development of overactive bladder symptoms and incontinence [36]. Anecdotal reports have led to a long list of potential dietary culprits: chocolate, citrus fruits and juices, tomatoes and tomato-based products, vinegars, dairy products, aspartame, and spicy foods. Identification of specific offending substances through systematic dietary manipulations can provide beneficial improvement in symptoms in some patients. In those women with atrophic vaginitis, local hormonal supplementation may reduce irritation and OAB symptoms. A small amount of estrogen cream (Premarin, Estrace) placed just inside the vagina on a nightly basis for 2 weeks, followed by a maintenance regimen of three times per week, can contribute to the resolution of OAB symptoms. Various bladder training techniques have been used to re-establish cortical control of bladder function by training patients to void following appropriate conscious signals [37]. Habit training is used for patients with problematic urinary frequency. They are instructed to void at preset intervals, while awake, and progressively increase the intervals by consciously postponing micturition. The appropriate timing of the initial interval is determined following evaluation of the patient’s baseline voiding frequency from a voiding diary. Patients are then encouraged to adhere to a rigid program of micturition, with intervals between 3 and 4 hours as the ultimate goal. Learning to ignore or suppress interval urges to urinate through various distraction techniques (ie, mental exercises) is another part of the cognitive training. Although objective evidence is lacking, it is theorized that bladder training acts by increasing cortical inhibition over the sacral micturition reflex center. Scheduled toileting is another voiding technique that simply involves timed voiding, usually every 2 to 3 hours, without manipulation of the interval. Generally used for patients who are not independent with their activities of daily living, the strict schedule is an attempt to keep them dry by encouraging micturition before the sensation of bladder fullness, urgency, or incontinence occurs.

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Another successful therapeutic modality for incontinence has been the use of pelvic floor exercises (PFEs) developed by Kegel [38,39] in the 1940s. The initial concept behind pelvic floor rehabilitation involved strengthening the striated musculature of the pelvis to increase muscle tone, pelvic support, and urethral resistance, and thereby decrease episodes of incontinence. This was accomplished by gradually increasing the number and duration of voluntary contractions of the levator muscles. It has since been shown that the sudden urge to urinate can be suppressed by rhythmic contraction and relaxation of the pelvic floor muscles. Such rapid, active pelvic floor muscle contractions can influence neural reflexes between the urethral sphincterpelvic floor mechanism and the bladder, and inhibit the sudden unwanted bladder contractions associated with urgency and urinary incontinence. Successful PFEs begin with identification and isolation of the pelvic floor musculature. Direct clinician-patient biofeedback is generally required to ensure the exercises are performed properly. The patient is instructed to contract or squeeze her vaginal muscles, as if she were attempting to stop the flow of urine during voiding. With the examiners two fingers placed in the vaginal vault, gentle circumferential pressure should be observed, which elevates and moves the fingers toward the posterior vaginal vault, thereby indicating a successful pelvic floor contraction of adequate strength. Neither abdominal straining (Valsalva’s maneuver) nor gluteal contractions are associated with properly performed PFEs. Breath-holding during contractions is also discouraged. Very motivated patients can be instructed to use this two-finger maneuver to identify the appropriate muscles on their own at home. Even after clinical instruction, however, some women find it difficult to isolate the pelvic floor muscles, and are unable effectively to perform the appropriate exercises. For these patients, biofeedback with pressuresensitive and electromyographic devices was developed to help identify and isolate the specific muscles for training. Some studies have shown improvements in motivation and compliance through biofeedbackenhanced regimens, which translated to improvements in symptoms [40]. For those patients who do not have trouble identifying the appropriate muscles, however, PFEs supported by sophisticated biofeedback devices are often unnecessary. Several studies have failed to show a clinical difference between properly performed PFEs alone (initially instructed by verbal cues) versus PFEs with biofeedback [41–43]. Once the proper pelvic muscles have been identified, the patient learns to use these muscles for the purpose of urinary urge suppression. When faced with the sudden urge to urinate, the patient is instructed to resist the immediate desire to run to the toilet; rather, she should stop, relax, and consciously perform isolated pelvic floor muscle contractions. Short, 2- to 3-second contractions, followed by similar-duration relaxations, are repeated (usually 10 to 15 times) until the precipitous desire to urinate abates. Following cessation of the urgency episode, the patient should then walk calmly to the toilet to void.

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Although several studies have shown the benefit of behavioral and exercise therapies for reducing symptoms of urge incontinence, not all patients are able to achieve complete continence with these maneuvers. Combining these modalities with pharmacotherapy, however, has resulted in even better results [44–46]. A recent randomized crossover-design study revealed an 85% reduction in urge incontinence after a trial of combined behavioral and drug intervention, as compared with 72% and 57% reductions after only drug or behavioral modalities, respectively [45]. Pharmacotherapy for urinary incontinence has focused on anticholinergic, antimuscarinic agents that block the parasympathetic signals to the detrusor muscle and inhibit involuntary bladder contractions (Table 5). The clinical effect is seen as an increase in functional bladder capacity, a reduction in diurnal voiding frequency, and a diminished sense of urgency and urge-incontinent episodes. The use of anticholinergic medications as first-line drug therapy for OAB and urinary incontinence is supported by systematic reviews of randomized, placebo-controlled trials involving various pharmacologic modalities [47]. Superior efficacy of anticholinergic medications for the control of urinary incontinence has been repeatedly established. The immediate-release anticholinergic oxybutynin chloride (Ditropan IR) has been used effectively for many years. Long-term compliance is problematic, however, because of intolerable anticholinergic side-effects, such as dry mouth; constipation; blurred vision; nausea; dizziness; headache; and, in some cases, altered cognitive function. The bioavailability of oxybutynin is only about 5% to 10% after administration of an immediate-release oral dose form, with a half-life of 2 to 3 hours. Presystemic metabolism of oxybutynin produces high plasma concentrations of N-desethyloxybutynin, an active metabolite that is primarily responsible for the undesirable side effects associated with oxybutynin therapy. The development of an extended-release form (Ditropan XL) results in a constant plasma concentration over a 24-hour period. By bypassing many of the enzymes that metabolize oxybutynin in the upper

Table 5 Antimuscarinic drugs Generic name

Trade name

Dosage

Propantheline bromide Flavoxate hydrochloride Hyoscyamine sulfate Imipramine hydrochloride Dicyclomine hydrochloride Oxybutynin chloride (immediate release) Oxybutynin chloride (extended release) Oxybutynin chloride (transdermal patch) Tolterodine tartrate (immediate release) Tolterodine tartrate (extended release)

Pro-Banthine Urispas Levsin, Levsinex Tofranil Bentyl Ditropan IR Ditropan XL Oxytrol Detrol Detrol LA

15–30 mg tid-qid 100–200 mg bid-qid 0.125 mg qid, 0.375 mg bid 10–50 mg bid 20 mg tid 2.5–5 mg tid 5–30 mg qd 3.9 mg/d patch (applied Q 4 d) 1–2 mg bid 2–4 mg qd

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gastrointestinal region, oxybutynin extended release reduces the presystemic metabolism and the formation of active metabolite. Although providing similar or enhanced efficacy, the extended-release, once-daily formulation of oxybutynin has shown greater tolerability when compared with the immediate-release, three-times-daily formulation [48,49]. Similar findings are associated with the anticholinergic tolterodine tartrate (Detrol). Unlike the other antimuscarinic drugs, however, tolterodine expresses a higher selectivity for the muscarinic receptors within the bladder, as compared with the salivary glands, and is considered to be uroselective. Clinically, this selectivity is associated with fewer anticholinergic side effects (ie, dry mouth) when compared with the traditional nonselective antimuscarinics [50,51]. Also available in a once-a-day, extended-release formulation (Detrol LA), tolterodine extended release may prove superior with respect to patient tolerability and compliance. Recently approved by the Food and Drug Administration for use in the management of OAB and urinary incontinence is the transdermal delivery form of oxybutynin (Oxytrol). This transdermal patch completely avoids the presystemic metabolism of oral formulations and thereby greatly reduces the plasma concentrations of the active metabolite [52]. While maintaining comparable efficacy, a significant improvement in the anticholinergic side effect profile when compared with oral oxybutynin administration has been shown [53,54]. Even greater improvements in bladder symptoms have been seen in some women with the addition of imipramine (Tofranil) to oxybutynin or tolterodine, because of the synergistic effects associated with combination therapy. When using imipramine, it is advised to start with a low dose (10 mg at bedtime), followed by small incremental increases over time as needed. Caution should be exercised in the elderly. Regardless of the specific agent or delivery system used, patients should be advised that a 2- to 4-week trial of antimuscarinic therapy is frequently needed before maximal benefit can be established [55]. Recalcitrant urge incontinence should elicit a referral to a specialist for continued evaluation using specialized diagnostic modalities to identify accurately the pathophysiologic etiology of the incontinence. Alternative treatment modalities within the armamentarium of an urologist continue to focus on inhibition of bladder contractions. These modalities include sophisticated pelvic floor retraining incorporating pressure-sensitive perineometers for biofeedback; cystoscopic bladder hydrodistention; intravesical instillation of neurotoxins causing desensitization of afferent sensory neurons in the bladder (ie, capsaicin [56], resiniferatoxin [57]); and neuromodulation of sacral nerves, which influence neural reflexes to the bladder, sphincter, and pelvic floor (InterStim) [58,59]. Another promising treatment option currently under investigation involves injections of botulinum toxin (Botox), an inhibitor of acetylcholine release at the neuromuscular junction, directly into the bladder wall to abolish unwanted

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bladder contractions [60]. Aggressive surgical management, such as bladder augmentation and urinary diversion, is reserved for severe recalcitrant cases of OAB and urinary incontinence and should be used as a last resort. Stress incontinence Rehabilitation and strengthening of the levator muscles with PFEs have demonstrated a 50% to 75% reduction in symptoms in some women with SUI [1]. When the objective is to strengthen the pelvic floor musculature, a daily exercise regimen is advised. Although Kegel’s [38] original recommendation included 300 daily PFEs to ensure adequate pelvic floor strengthening, more recent recommendations, based on general strengthtraining principals [61], suggest that a regimen of 24 to 36 contractions per day is adequate [62]. A practical strengthening regimen for PFEs involves 2to 3-second contractions (squeezes), with 10 to 15 contractions per session, and three sessions per day. Although a trial of properly performed PFEs for the treatment of SUI is justifiable, the subjective degree of improvement experienced by many women is frequently unsatisfactory. Mechanical or surgical interventions are frequently required to re-establish complete continence. A variety of urethral support or occlusion devices are available for the patient who requires only intermittent treatment (ie, during strenuous activity). Vaginal pessaries provide anatomic support to the pelvic floor and inhibit downward descent of the urethra during times of abdominal straining [63–65]. Urethral occlusion devices include disposable plugs, which directly block the urethra and prevent urinary leakage (ie, FemSoft Insert) [66,67]. Although these cork- type devices sound attractive, in practice most women do not find them tolerable. Ultimately, many women require surgical intervention to regain complete continence. Although many anti-incontinence procedures have been tried over the years, only the transabdominal Burch suspension [68], autologous fascial sling [69], and the mid-urethral synthetic mesh sling [70] procedures have demonstrated 85% long-term ([5 year) success. For some patients with SUI primarily caused by poor urethral coaptation, periurethral injection of bulking agents improves urethral resistance to leakage. The most widely used agent is collagen, but silicone and pyrolytic carbon beads are also used. Short-term cure rates (measured in months) are about 50%, but effectiveness deteriorates over time, requiring repeat injections for maintenance of continence [71,72]. Implantable artificial urinary sphincter prosthetic devices, rarely needed in women, are for those severe cases when all else has failed. A new and promising drug for the treatment of SUI is the combined serotonin and norepinephrine reuptake inhibitor, duloxetine. Increasing levels of these neurotransmitters in the sacral spinal cord enhances pudendal nerve activity, which promotes increased contraction of the urethral

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sphincter. Preliminary data from clinical trials support the use of duloxetine for the treatment of women with SUI, noting at least a 50% reduction in incontinence episodes in more than half the women evaluated [73]. Approval by the Food and Drug Administration is pending. Mixed-type incontinence The basic principle for the treatment of mixed-type incontinence (UI and SUI) is to direct the initial treatment at the symptom that predominates and causes the greatest bother or morbidity to the patient. If the second form of incontinence persists or becomes apparent after the first is treated, the second also should be treated. Commonly, the symptoms of urgency, frequency, and urge incontinence produce the greatest negative impact on quality of life, because the nature and timing of these symptoms are often unpredictable. When in doubt, it is reasonable to begin with noninvasive behavioral, rehabilitative or medical treatment options for the frequency and urgency symptoms before considering surgical therapy for the symptoms of SUI. Overflow incontinence Overflow incontinence is a sign of relative urinary retention. The treatment involves facilitating appropriate bladder emptying. Identifying the etiology of the urinary retention is the first step. Urinary retention occurs as a result of one of two things: an inability of the bladder muscle to produce an adequate contraction, or an anatomic or functional obstruction to the outflow of urine. Some patients with poor detrusor contractility may benefit from a trial of bethanechol (Urecholine), a cholinergic agent that has selectivity for the bladder (and gastrointestinal tract) [74]. Oral bethanechol, 25 to 100 mg four times daily, may be used. The potential side effects, however, are many and often prove limiting: flushing, nausea, vomiting, diarrhea, bronchospasm, headache, salivation, sweating, and visual changes. Results with respect to adequate bladder emptying have been variable [75]. In cases of severe detrusor hypocontractility, a regimen of intermittent straight catheterization or a chronic indwelling catheter may be required. Bladder outflow obstruction in the female is rare, and is usually associated with significant pelvic organ prolapse, a prior anti-incontinence procedure, or other anatomic abnormalities of the urethra. Identification of such a problem warrants referral to a specialist for further diagnostic evaluation and treatment. Functional incontinence Functional incontinence results from physical or cognitive impairments, which prevent the patient from proceeding to a toilet in a timely fashion to perform independent toileting skills. Adhering to a regimen of timed voiding

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(every 2 to 4 hours) can help prevent the uncontrollable urgency often associated with a full bladder. Mobility-assist devices, bedside commodes, or routine nursing care may be necessary, depending on the degree of mental or physical disability. Transient incontinence Proper identification of the inciting factors for transient incontinence is the key to successful treatment. Reversible causes, as previously outlined by the mnemonic DIAPPERS, should be aggressively treated. Although the incontinence may be transient in nature, it can persist if left untreated. Continuous and postvoid incontinence Continuous urinary leakage or dribbling, unrelated to activity or stress maneuvers, and without a sensation of bladder fullness or urgency, is usually related to an anatomic abnormality, such as a urethral diverticulum or a urinary fistula. Such symptoms warrant referral to a specialist for further diagnostic evaluation. Surgical correction is usually required.

Summary Contrary to the belief of some patients and physicians, urinary incontinence in women should not be accepted as a natural and inevitable part of aging. Indeed, it is a costly problem, psychologically, physically, and economically, and can have a considerable impact on a woman’s quality of life. Accurate diagnosis of the type of incontinence is important to implement appropriate and successful treatment. In general, a focused medical and symptom-oriented history and physical examination is all that is needed to establish the correct diagnosis. UI, SUI, and mixed incontinence are the most common types seen in women. Most patients with urge incontinence respond to behavioral treatments, PFEs, medication, or some combination thereof. Recalcitrant cases should be referred to a specialist. Patients with SUI may respond to PFEs, but many require surgical intervention for a satisfactory outcome. The successful treatment of urinary incontinence in a woman can lead to a substantial improvement in her overall quality of life, and for the physician, can be as professionally rewarding as the successful management of various other chronic disease states.

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