Modern Management of Women with Stress Urinary Incontinence: Part 1

    Female urinary incontinence (UI) is defined as any involuntary leakage of urine in women. The three common types of UI are stress, urge, and mixed. Stress urinary incontinence (SUI) is the leakage of urine with physical exertion, exercise, coughing, or sneezing in the absence of a bladder contraction.

Urge incontinence is leakage associated with a strong and urgent desire to void. Mixed incontinence is any combination of the two. Urinary incontinence can have a major negative impact on a woman’s quality of life. This paper reviews some of the options available to address SUI.

    The exact prevalence of female UI is difficult to determine because the definition can be variable and, due to the nature of the disease, is likely to be underreported and under diagnosed.¹ Despite this confusion, UI undoubtedly affects millions of women worldwide, and according to one estimate, more than $16 billion is spent on its treatment.² 

    Female urinary continence is multifactorial. It depends on intact neurologic, muscular, vascular, and fascial support components. The pelvic floor muscles include both smooth and striated muscles, which are innervated by sympathetic, parasympathetic, or somatic nerves that must be functional in order for contraction and relaxation to occur. Proper muscle function is facilitated by intact ligaments and fascia.

    Stress urinary incontinence occurs when a deficiency exists in any of the above components and the pressure in the bladder is greater than the resting urethral pressure, allowing passive flow of urine. Multiple risk factors are associated with SUI. The most commonly cited are age, obesity, and vaginal delivery.^3,4 Others include hysterectomy, menopause, prior pelvic surgery or radiation, smoking, constipation, and medications.

    Evaluation of a patient with SUI must include a thorough history of voiding symptoms as well as the impact of SUI on quality of life. Urinalysis and cultures should be performed. Physical exam must include both a neurological and pelvic exam with an attempt to reproduce the incontinence. The need for diagnostic studies is controversial but may include urodynamics, videourodynamics, and cystoscopy.

    An understanding of the physiology, pathophysiology, and pharmacology of the lower urinary tract permits appreciation of the various etiologies of SUI as well as the rationale behind therapy. General treatment options include behavioral therapy, pelvic floor muscle exercises, biofeedback, pharmacotherapy, and surgical interventions.

Behavioral Therapy

    Behavioral modifications aim to decrease the magnitude of stress on the bladder. This may be facilitated by education, weight loss, and specific exercises. Because of the noninvasive nature of the therapy, behavioral modification is often used as the initial step in treatment. The educational component is important and allows the patient to understand and respond to her body. A voiding log or diary is a necessary first step and should include fluid intake as well as all incontinent episodes and symptoms. This documentation helps the physician recommend fluid restriction if excessive intake is noted and timed voiding if large time intervals between voids exist or if large volumes are noted at each void. Urge suppression can be particularly helpful if the patient is experiencing a strong desire before leakage occurs.⁵

    Pelvic floor muscle exercises (PFME), or Kegel exercises, may improve incontinence in women with SUI.⁶ These exercises work by isolating and strengthening the levator ani muscles, the major muscle group supporting the pelvic floor. Contraction of these muscles can increase urethral resistance and improve support of the bladder neck. Pelvic floor muscle training may be unsuccessful if the cause of the incontinence is not due to muscle weakness, but rather to another issue such as loss of connective tissue support.⁷ However, by strengthening and improving the pelvic floor muscles, it is possible to compensate for other deficiencies. Kegel exercises may cause synergistic contraction of the urethral sphincter and can produce a significant increase in maximum urethral resting pressure. The subjective short-term cure rates may vary between 60% to 75%.⁸ Unfortunately, long term effects and results are not known.

    The proper muscle training emphasizes both slow and fast contraction of the isolated muscles groups with the goal of improving both strength and endurance. This will help build structural support for the bladder and urethra, prevent descent, and allow patients to voluntarily contract the muscles during times of increased intra-abdominal pressure and thus prevent incontinence. Many women mistakenly contract the gluteal or abdominal musculature or incompletely exercise the levator ani muscles. Therefore, simply telling a patient to perform these exercises is often insufficient. An appropriate referral to a trained medical specialist may be important to minimize patient frustration as well as maximize therapeutic benefit.

    The use of biofeedback as well as electrical stimulation may aid in training.⁹ Biofeedback requires the use of instrumentation or EMG to train the patient to control her bodily function. It is the information provided, or the feedback, on their bodily function that allows patients to exhibit or improve control. The use of biofeedback in combination with pelvic floor exercises may improve results over pelvic floor exercises alone.⁹ Vaginal cones can be used as biofeedback instrumentation. The cone is placed in the vagina and the patient is instructed to contract the muscles that will hold the cone in place and prevent it from slipping out. The feedback includes the sensation of the cone slipping out of the vagina or the continued suspension in the case of appropriate muscle contraction. Electrical stimulation is a noninvasive, passive treatment that produces a muscle contraction. This is believed to improve muscle strength but the efficacy of this treatment is questioned. In one randomized controlled study in which 200 patients were followed, the use of pelvic floor electrical stimulation did not lead to improved continence over pelvic floor exercises alone.¹⁰

Pharmacology

    The bladder neck and proximal urethra contain a preponderance of alpha-receptors and possibly of beta-receptors that when stimulated augment urethral tone in the continent patient. Theoretically, manipulation of these receptors should alter outlet resistance.¹¹ However, pharmacotherapy for the treatment of SUI has been limited due to the lack of specificity of the drugs proposed to act on these receptors. This non-specificity contributes to the wide range of side effects and questions regarding product safety.¹² Although some drugs have been shown to decrease the incidence or magnitude of incontinence, the adverse side effects make them clinically impractical. In fact, drug therapy for SUI was considered by some to be a thing of the past.

    Traditionally a variety of medications have been used to treat SUI, including alpha-adrenergic agonists, beta-adrenergic agonists and antagonists, estrogens, and tricyclic antidepressants.¹³ None of these drugs have obtained FDA approval for treatment of SUI.

     Alpha-adrenergic agonists. The alpha-adrenergic agonists, as a group, have been implicated as the most potentially beneficial for patients suffering form SUI. Because urethral smooth muscle tone is mediated by norepinephrine (NE) activation of alpha-receptors, the use of alpha adrenoreceptors agonists would presumably increase the urethral smooth muscle tone, increase urethral closing pressure, and decrease incontinence.¹⁴

    A number of these medications have been evaluated for their potential use in the treatment of SUI. These include ephedrine, pseudoephedrine, phenylpropanolamine (PPA), and midodrine. Although some of these drugs have been shown to decrease frequency and amount of urinary incontinence in patients with mild to moderate SUI, their use was discontinued due to their lack of lower urinary tract specificity and their side effect profile.¹³ Side effects include palpitations, hypertension, arrhythmias, headache, sleep disturbance, and potentially lethal side effects such as hemorrhagic stroke.¹⁵ These side effects can occur as early as 1 to 6 hours after drug administration and tend to occur in less than 10% of patients.¹⁵ Phenylpropanolamine has been taken off the market in the US due to an increased incidence of stroke.

    Estrogen. Estrogen use for the treatment of SUI is controversial. Estrogen receptors have been identified in the vagina, pelvic floor muscles, and lower urinary tract.¹⁶ Topical or systemic estrogens are believed to thicken the urethral mucosa, perhaps via increased vascularity of the tissue; hence, allowing for a better apposition and seal of the urethra.¹⁷ Estrogens are also thought to increase the alpha-adrenergic response possibly as a result of an increase in the number of receptors; inadequate testing has failed to give definitive proof of its merits.¹⁸

    Tricyclic antidepressants. Tricyclic antidepressants (specifically, imipramine) have been used in the treatment of SUI. This drug has anticholinergic, smooth muscle relaxant, and NE/serotonin uptake inhibition properties; thus, it is believed to facilitate urinary storage by decreasing bladder contractility and increasing outlet resistance.¹² However, a vast array of side effects has been noted. These include dry mouth, weakness, fatigue, sedation, manic or schizophrenic picture, Parkinsonian effects, fine tremor, orthostatic hypotension, excessive sweating, orgasmic impotence, and arrythmia.¹³ Unfortunately, no placebo-controlled clinical studies have been conducted for its use in SUI.

    Duloxetine. The most promising therapy on the horizon is duloxetine, a balanced serotonin-norephinephrine (5-HT/NE) reuptake inhibitor. The proposed mechanism includes increase in neurotransmitters at the level of the spinal cord (Onuf’s nucleus), which creates an increase in urethral rhabdosphincter activity via the pudendal nerve.¹⁹ The improvement in pelvic floor tonus is believed to augment urethral resistance. Animal studies have shown increased EMG activity in the pelvic floor muscles following use of duloxetine.¹⁹

    Duloxetine will be the first FDA-approved medication for SUI. The drug is slated for distribution in the US in the next few months. After undergoing double-blind placebo controlled studies, it has shown significant improvements in pad tests, number of incontinence episodes, and quality of life.²⁰ A North American, double-blind placebo-controlled study enrolled 683 women with a weekly incontinence episode frequency (IEF) of 7 or greater. Each patient received either placebo or 80 mg of duloxetine daily for 12 consecutive weeks. In the treatment group, 51% experienced a 50% to 100% decrease in incontinence episode frequency compared to 33% of patients in the placebo group. The treatment group also had a statistically significant improvement in quality-of-life parameters compared to the placebo arm. The most common side effect is nausea, occurring approximately 22% of women, followed by fatigue, insomnia, and dry mouth in approximately 15%, 14%, and 12%, respectively.²⁰ Recent reports have suggested that duloxetine may increase blood pressure; the clinical significance of this has yet to be determined.