Fluid States: Concepts in Urinary Incontinence

From the 45th Annual Northern Michigan Summer Conference: Update on Common Clinical Concerns in Primary Care, sponsored by the University of Michigan Medical School, Ann Arbor

J. Quentin Clemens, MD, Associate Professor of Urology, and Director, Division of Neurourology and Pelvic Reconstructive Surgery, University of Michigan Medical School, Ann Arbor

Educational Objectives

The goal of this program is to improve management of urinary incontinence in women and lower urinary tract symp­toms (LUTS) in men. After hearing and assimilating this program, the clinician will be better able to:

1.   Distinguish stress incontinence from urge incontinence.

2.   Select effective treatment of incontinence, based on symptoms.

3.   Describe efficacy and side effects of medications commonly used to treat incontinence.

4.   Approach management of LUTS, based on clinical findings and severity of symptoms.

5.   Choose appropriate behavioral, medical, and invasive therapies for LUTS.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Clemens and the planning committee reported nothing to disclose. Dr. Clemens presents information in his lecture that is related to off-label or investigational use of a therapy, product, or device.

Acknowleldgements

Dr. Clemens spoke in Bellaire, MI, at the 45th Annual Northern Michigan Summer Conference: Update on Common Clinical Concerns in Primary Care, presented June 22-26, 2009, by the University of Michigan Medical School. The Audio-Digest Foundation thanks Dr. Clemens and the University of Michigan Medical School for their cooperation in the production of this program.

Urinary Stress Incontinence

Stress incontinence: involuntary urine loss with increases in intra-abdominal pressure (eg, coughing, sneezing); pathophysiology  —  weak urethral sphincter mechanism; not well understood; can be improved with surgery; multi­factorial; some women predisposed; trauma (eg, childbirth, cesarean delivery); age

Evaluation: patient history important; tolterodine (eg, Detrol) or oxybutynin (eg, Ditropan) unlikely to help; consider urodynamic testing in patients with unclear or mixed-type incontinence; trial with drugs may be helpful; many pa­tients have mixed stress and urge incontinence symptoms (consider nonsurgical treatment [eg, drugs, physical ther­apy] first); consider how bothersome patient finds symptoms; pelvic examination  —  check bladder and urethra for prolapse; prolapse and incontinence commonly coexist; assess pelvic floor muscle strength; red flags  —  neurologic disorder (eg, multiple sclerosis [MS], stroke); history of pelvic surgery or pelvic irradiation; lack of response to treatment; consider early referral; medication history  —angiotensin-converting enzyme (ACE) inhibitors (cause cough); caffeine; diuretics; laboratory studies  —  urinalysis (UA) for hematuria or infection

Modifiable risk factors: study found weight loss beneficial; pelvic floor education — provided by physical therapist or nurse; bladder training  —  probably more effective for urge incontinence; frequent voiding can prevent bladder leakage with coughing or sneezing; pelvic floor muscle training  —more effective for stress incontinence; provide verbal or written instructions; active therapy (eg, strength training with vaginal cones); electrical stimulation  —  causes involuntary spasms of pelvic muscles; 50% of women unable to perform Kegel exercises correctly; real-time feedback with digital vaginal assessment, or use of vaginal cones or anal sensors; behavioral therapy  —  effective for stress and urge incontinence; pelvic floor muscle therapy may add more benefit; pessaries  —  prevent prolapse of vaginal wall; surgical repair of large cystocele can unmask stress incontinence; urethral inserts  —  not commonly used due to inconvenience and risk for bladder irritation or infection

Medications: no agents approved by Food and Drug Administration (FDA); duloxetine (Cymbalta) associated with increased risk for suicide; off-label use of imipramine (antidepressant), a-agonists (eg, pseudoephedrine), and oth­ers sometimes used without significant benefit

Surgery: mainstay of therapy; »200,000 surgeries performed per year for prolapse and stress incontinence; injection therapy  —  least invasive; substance (eg, collagen) injected into urethral tissue via cystoscope; 1 to 2 injections initially, followed by injections every 1.0 to 1.5 yr; may be less effective in more active women; generally re­served for elderly patients; »2% of women allergic to collagen (perform skin test; some synthetic substances available)

Definitive surgical repair: effective; recurrence rate after prolapse repair, 30%; Burch colposuspension  —  tissue ad­jacent to urethra sutured and secured near pubis; pubovaginal sling  —  instrument passed out of vaginal incision; material (eg, rectus fascia, synthetic mesh) pulled on each side and sutured above rectus muscle, remaining under urethra; recent randomized trial found at 24 mo, sling reduced incontinence better than colposuspension, but as­sociated with more complications (eg, voiding difficulties, urge incontinence); standard sling requires bikini line incision (most women must use urinary catheter for 1-2 wk after); mesh slings require smaller incision and have shorter recovery time (often performed as outpatient procedures); contemporary meshes safe; complications in­clude mesh exposure and erosion into vagina and injury (to, eg, bladder, bowel, or blood vessels [rare]); public health notification released by FDA reported »1000 cases of mesh complications from 9 surgical manufacturers (small percentage of total procedures); obtain informed consent

Urge Incontinence

Overactive bladder (OAB): urinary urgency  —  cardinal symptom of OAB; desire to pass urine sudden, compelling, and difficult to defer; OAB dry  —  urgency without incontinence; OAB wet  —  urgency with incontinence

Pathophysiology of OAB: poorly understood; abnormal afferent processing (eg, signal sent by bladder wall tension receptors abnormally strong); abnormal central processing (eg, after stroke); abnormal efferent impulses to bladder cause spasms (target of antimuscarinic drugs)

Prevalence: 30% to 35%; OAB wet more common in women; OAB dry more common in men; symptom of urgency common

Evaluation: thorough patient history; assess severity (eg, type and number of absorbent pads used, volume of leak­age, duration of symptoms, degree of bother); look for pelvic prolapse; positive cough test for leakage confirms stress incontinence; red flags  —  neurologic disease; history of pelvic surgery or pelvic irradiation; lack of response to treatment; medication history  —  diuretics; caffeine (more likely to trigger symptoms of urge incontinence than stress incontinence); UA for hematuria, pyuria, and glucosuria

Modifiable risk factors: patients with pyuria and bacteriuria likely to have treatable urinary tract infection (UTI); re­duce, change, or adjust diuretic dosage; avoid caffeine use; bedside commode for patients with restricted mobility; address constipation and bowel dysfunction (consider effects of medications), altered mental status, and obesity (weight loss can improve symptoms)

Conservative therapy: educate patient about bladder function, causes of incontinence, and urge-control strategies; urge-suppression strategy  —  “do not rush to toilet; stop and stay still; squeeze pelvic floor muscles; relax body; concentrate on suppressing urge; wait until urge subsides, then slowly walk to restroom”; behavioral therapy (ie, bladder training) showed 81% reduction in urge incontinence (69% reduction with medications, 39% with con­trols); other studies show combined medication and behavioral therapy more effective

Medications: mainstay of treatment; block transmission to M2 and M3 muscarinic cholinergic receptors in bladder detrusor muscles; agents differ in relative affinity for M2 or M3, but clinical difference “very little”; oxybutynin (eg, Ditropan)  —  tid dosing; Ditropan XL metabolized throughout gastrointestinal (GI) tract (taken once daily); toltero­dine (eg, Detrol)  —  bid dosing (Detrol LA taken once daily)

Newer drugs: transdermal oxybutynin  —  1) Oxytrol; transdermal patch changed twice weekly; can cause skin irrita­tion, but no other side effects commonly seen with other antimuscarinic agents; 2) Gelnique; gel applied daily; oral agents  —  1) trospium (Sanctura bid or Sanctura XR once daily); 2) darifenacin (Enablex); 3) solifenacin (Vesicare); 4) fesoterodine (Toviaz)

Efficacy of medications: Cochrane review of 61 trials  —  in »12,000 subjects, placebo response rate 41% (demon­strates effectiveness of bladder training); additional 15% benefit with active treatment (number needed to treat [NNT], 7); average of 4 fewer leakage episodes and 5 fewer voids per week; dry mouth rate 3-fold higher for active therapy, compared to placebo; other study  —  no clear difference in efficacy between agents; lower rate of side ef­fects (especially dry mouth) with newer, once-daily agents; generic oxybutynin (tid) associated with higher with­drawal rate due to higher rate of side effects; presently, industry-funded (biased) studies only

Side effects: dry mouth; constipation; dry eyes; blurry vision; headache; facial flushing; gastroesophageal reflux symptoms; palpitations (rare); contraindications  —  uncontrolled narrow-angle glaucoma; gastric emptying disor­der; urinary retention

Medication adherence: fairly poor; at 1 yr, 70% to 90% discontinue medications; adherence to newer medications appears better than adherence to generic oxybutynin; avoid generic, immediate-release oxybutynin (tid) unless only option (eg, only agent covered by insurance); pick 2 other oral drugs and become familiar with dosing; consider of­fering transdermal medication to patients who cannot tolerate side effect of dry mouth

Mixed incontinence: ³50% of women have stress and urge incontinence symptoms (determine which more severe); can be improved with conservative therapy; consider trial of antimuscarinic therapy to assess response before com­mitting to surgery; urodynamic testing can help determine treatment

Treatment of refractory urge incontinence: sacral neuromodulation  —  small lead placed through S3 sacral nerve root; low level of electrical stimulation applied to lead stimulates nerves to bladder, causing urge suppression; ap­proved by FDA in 1997; 4-day trial of external battery used to assess response; small lead can be placed in office under local anesthesia; some patients require surgical placement of larger lead for longer test periods; success rate, »80%; also used for urinary retention (success rate, »50%); battery lasts 5 to 8 yr; covered by insurance; botulinum toxin type A (eg, Botox)  —  off-label use; prevents neurotransmitter release at neuromuscular junction; temporary ef­fect; requires repeated injections into bladder with cystoscope; expensive; trial under way

Male Lower Urinary Tract Symptoms

Terminology: benign prostatic hyperplasia (BPH)  —histologic; tissue obtained from prostate shows hyperplasia; benign prostatic enlargement (BPE)  —  prostate enlarged, based on comparison of prostate size of typical healthy man 18 yr of age (»20 g); can assess with rectal examination (not highly accurate), transrectal ultrasonography, or magnetic resonance imaging (MRI); bladder outlet obstruction (BOO)  —  diagnosed by urodynamic testing; often due to BPE from BPH; prostatism  —  antiquated term

Lower urinary tract symptoms (LUTS): voiding symptoms  —slow stream; straining to void; hesitancy; sense of in­complete bladder emptying; storage symptoms  —  urgency with or without urge incontinence; frequency; nocturia; symptoms overlap (difficult to objectively diagnose patients); measured with symptom scoring questionnaire

Evaluation: thorough history; characterize symptoms; identify most bothersome symptoms; look for red flags and complicating factors (eg, urologic surgery, urologic disease, radiation therapy, urinary tract cancer); physical examination  —  rectal examination; palpate bladder; laboratory and imaging studies  —  UA; prostate-specific anti­gen (PSA) screening not recommended for asymptomatic patients; urine cytology for patients with high-risk fac­tors for bladder cancer (eg, tobacco smoking with hematuria); BPH most common cause of hematuria in men >50 yr of age; checking for appropriate bladder emptying with ultrasonography can be helpful; PSA  —  refer patients if examination or PSA abnormal; normal PSA <1 ng/mL; not appropriate to consider PSA of 3.8 ng/mL normal in man 42 yr of age; age-adjusted PSA values lower threshold in younger men, and raise threshold in older patients; low specificity (possibly better marker for BPH than for prostate cancer); 25% of men with diagnosis of BPH and negative biopsy have PSA >4 ng/mL

Behavioral therapy: caffeine can irritate bladder and cause voiding symptoms; alcohol may contribute to symptoms; voiding diary  —  patient records amount and time of drinking, and amount and time of voiding for 2 or 3 days; use­ful if primary complaint urinary frequency or nocturia; can help determine whether frequency normal (8-10 times/day) and help manage fluid retention

Watchful waiting approach: most appropriate for men with milder and less bothersome symptoms; degree of bother number one predictor of success of therapy; annual follow-up to track symptoms over time; repeat PSA screening as appropriate

Phytotherapeutic agents: eg, saw palmetto; often ineffective

b-blockers: doxazosin and terazosin  —  available in generic forms; nonspecific (can be used to treat blood pressure); must be titrated up (eg, to 4 mg for doxazosin and 5 mg for terazosin); tamsulosin and alfuzosin (Uroxatrol)  —tamsulosin associated with 8% chance for retrograde ejaculation (not harmful, but may be bothersome to some men [consider Uroxatrol]); considered safe; efficacy similar

5-a reductase inhibitors: dutasteride (eg, Avodart) and finasteride (eg, Proscar)  —  available in generic form, but still expensive; block conversion of testosterone to dihydrotestosterone in prostate, leading to 20% reduction of prostate volume; after 6 mo of use, PSA levels decrease by 50% (multiply by 2 to obtain true PSA value); does not add specificity to PSA screening; less effective than b-blockers; not effective in men who do not have enlarged prostate; can be used preoperatively to reduce intraoperative bleeding during prostate resection; some sexual side effects (not common; eg, ejaculatory dysfunction, erectile dysfunction [rare]; decreased libido)

Antimuscarinic drugs: European study of men with obstructed flow placed on Detrol found rate of urinary retention exceedingly low; appear safe; numerous studies show efficacy; generally combined with a-blocker; start with a-blocker and consider adding antimuscarinic agent if patient does not respond (especially if symptoms related to ur­gency and frequency)

Management principles: treat possible nonurologic causes (eg, caffeine intake), especially in patients with fre­quency symptoms or lower extremity edema; check UA and PSA; take neutral approach to phytotherapies; use a-blockers liberally, and tailor treatment afterwards; urodynamic testing to document obstruction (if patient not obstructed, consider transurethral resection of prostate [TURP]); cystoscopy helpful

Invasive therapies: thermal-based therapy  —  microwave therapy or needle ablation (prostate heated to induce necro­sis and shrinkage over time); ablative therapy  —standard TURP (electrocautery devices used to remove pieces of prostate); transurethral incision of prostate for younger men; laser ablation (common; less bleeding; can be per­formed as outpatient procedure); open prostatectomy for greatly enlarged prostates; Botox  —  used for BPH or BPE; may induce necrosis of prostate and improve symptoms

Suggested Reading

Albo ME et al: Urinary Incontinence Treatment Network. Burch colposuspension versus fascial sling to reduce urinary stress in­continence. N Engl J Med 356:2143, 2007; Boyle P et al: UrEpik Study Group. The prevalence of lower urinary tract symptoms in men and women in four centres. The UrEpik study. BJU Int 92:409, 2003; Burgio KL et al: Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial. JAMA 280:1995, 1998; Kaplan SA et al: Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA 296:2319, 2006; Subak LL et al: Weight loss to treat urinary incontinence in overweight and obese women. N Engl J Med 360:481, 2009; Wein AJ et al: Achieving continence with antimuscarinic therapy for overactive bladder: effects of baseline in­continence severity and bladder diary duration. BJU Int 99:360, 2007; Wyman JF et al: Comparative efficacy of behavioral inter­ventions in the management of female urinary incontinence. Am J Obstet Gynecol 179:999, 1998.