Urinary Incontinence

Jan Busby-Whitehead, MDChief, Division of Geriatric Medicine University of North Carolina

University of North Carolina School of Medicine Center for Aging and Health

Definition of Urinary IncontinenceDefinition of Urinary Incontinence

* The International Continence Society

URINARY INCONTINENCEURINARY INCONTINENCE



PrevalencePrevalence

• Community: 17% older men, up to 30% older women

• Hospital: up to 50% older men and women

• LTCF: 50-70% older men and women


Hunskaar, et.al., Int Urogynecol J, 2000


Reversible causes of UI

- Delirium or Drugs

- Restricted mobility

- Infection, impaction

- Polyuria

IIPP

RRDD


Bladder Anatomy

Hollow, distensible, muscula organ

Reservoir of urine• Capacity ~600 mL• Desire ~200 mL• Normal void ~300 mL

Organ of excretion• Behind symphysis pubis• Female – against anterior wall of

uterus• Trigone• Sphincter


Physiology


Aging ChangesAging Changes

• Decreased bladder capacity

• Reduced voiding volume

• Reduced flow rates

• Increased urine production at night

* Nordling, J Experimental Gerontology, 2002, 37:991


Stress UIStress UI

The complaint of involuntary leakage with effort or exertion or on sneezing or coughing

Sudden increase in abdominal pressure

Urethral pressure

Abrams P et al. Urology. 2003;61:37-49.


Urge UIUrge UIAbrams P et al. Urology. 2003;61:37-49. Ouslander J. N Engl J Med. 2004;350(8):786-799.

The complaint of involuntary leakage accompanied by or immediately preceded by urgency Involuntary detrusor

contractions

Urethral pressure


Overactive bladderOveractive bladder

• Includes urinary urgency with or without urge incontinence, urinary frequency, and nocturia

• Associated with involuntary contractions of the detrusor muscle


Mixed UIMixed UI

The complaint of involuntary leakage associated with urgency and also with exertion, effort, sneezing, or coughing

Abrams P et al. Urology. 2003;61:37-49. Chaliha C et al. Urology. 2004;63:51-57.

Sudden increase in abdominal pressure

Involuntary detrusorcontractions

Urethral pressure


OverflowOverflow

Neurogenic/Atonic

Obstruction

•Urethral blockage•The Bladder is not able to empty properly


Functional IncontinenceFunctional Incontinence

• Immobility

• Diminished vision

• Aphasia

• Environment

• Psychological


Clinical QuestionsClinical Questions

? How do you evaluate for incontinence?

? Are behavioral techniques effective? For which patients?

? What drug treatments are useful and how do you use them?


Office Evaluation of UIOffice Evaluation of UI

• Identify presence of UI

• Assess for reversible causes and treat

• If UI persistent, determine type and initiate treatment

• Identify patient who needs further evaluation and referral


Basic Evaluation of UIBasic Evaluation of UI

• History: Bladder diary

• Physical examination, especially Genitourinary and Neurological

• Bladder stress test

• Postvoid residual

• Urinalysis, urine culture if indicated

• BUN, creatinine, fasting glucose


Referral CriteriaReferral Criteria

Recurrent urinary tract infections

Hematuria

Elevated postvoid residual or other evidence of possible obstruction

Recent gynecological or urological surgery or pelvic radiation

Failed treatment of stress or urge UI


CystometryCystometry

• Gold standard for diagnosis

• New definition for detrusor overactivity: Any rise in detrusor pressure during filling cystometry associated with symptoms and not related to abnormal bladder compliance

• Provocative stimuli

• Ambulatory monitoring


Treatment OptionsTreatment Options

• Behavioral

• Pharmacological

• Functional Electrical Stimulation

• Surgery


Are behavioral techniques effective? Are behavioral techniques effective? For whom?For whom?

• Behavioral techniques are effective for treatment of stress and urge UI, and overactive bladder, but generally do not cure

• Behavioral techniques are effective in community dwelling men and women

• Behavioral techniques are most appropriate for cognitively intact, motivated persons


Self ManagementSelf Management

• Fluid Intake

– Don’t reduce amount– Do not drink fluids 2 hr before bedtime– Avoid: caffeine, alcohol, nicotine


Scheduled VoidingScheduled Voiding

• Scheduled voiding with systematic delay of voiding– Schedule based on time interval pt can

manage in daytime– Void at scheduled time even if urge not

present; suppress urge if not time with “Quick Kegels”

– Increase voiding interval by 30 min each week until continent for up to 4 hr


Pelvic Muscle ExercisesPelvic Muscle Exercises

• Isolation of the pelvic muscles

• Avoidance of abdominal, buttock or thigh muscle contractions

• Moderate repetitions of strongest contraction possible

• Ability to hold contraction 10 seconds, repeat in groups of 10-30 TID


Range of Improvement

100

90

80

70

60

50

40

30

20

10

0

PMFE Without PMFE Without

BiofeedbackBiofeedback

PMFE With PMFE With

BiofeedbackBiofeedback

Range of Improvement

98%

50%

91%

38%


Randomized Trials of Behavioral Treatment Randomized Trials of Behavioral Treatment for Stress UIfor Stress UI

• 24 RCTs, but only 11 of high quality

• Pelvic floor exercises were effective (up to 75%)in reducing symptoms of stress UI

• Limited evidence for high vs low intensity

• Benefits of adding biofeedback unclear

* Berghmans et al. Br J Urol 1998:82:181-191


Behavioral Treatment for Urge/OABBehavioral Treatment for Urge/OAB

• Bladder training

– Initial approach

–3 RCT: 47-90% cure rate with 6 mo f/u

–Recurrence in 43-58% after 2-3 yr

–35% fewer UI episodes vs controls: Cochrane Review 2004


Limitations of Behavioral Treatment Limitations of Behavioral Treatment StudiesStudies

• Studies varied in

– types of UI– characteristics of subjects– intervention strategies– outcome measures used– duration of follow-up

• Few studies compared the efficacy of PFME performed with and without biofeedback


NIH Treatment TrialNIH Treatment Trial

Purpose:• Compare pelvic floor muscle exercises alone to

PFME plus biofeedback in women with stress and mixed urge and stress UI

• Design– 315 women randomized to 3 groups, including an

attention control group– Followup up at 2 weeks, 6 months, 1 year

Kincade, Dougherty, Busby-Whitehead


Drug Treatment for UI: What WorksDrug Treatment for UI: What Works

• Stress UI

– Alpha adrenergic agents?

– Estrogen?

– Combination therapy?


Alpha Adrenergic DrugsAlpha Adrenergic Drugs

• Phenylpropanoloamine– Once a first line drug– 8 randomized controlled trials– Study duration: 2-6 weeks– % cure: 0-14– % side effects: 5-33%

• WITHDRAWN FROM MARKET due to report of hemorrhagic stroke


Duloxetine Duloxetine (Cymbalta) (Cymbalta)

• FDA application for stress UI withdrawn

• Warning for liver dysfunction, alcohol


EstrogenEstrogen

• Combined study with Phenylpropanolamine suggested improvement in combination

• Improves urogenital atrophy

• Heart and Estrogen/Progestin Replacement Study 2001: 4 yr, randomized trial, 2763 postmenopausal women <80 given combined HRT or placebo for ischemic heart disease.– 55% had >1 episode UI/week– HRT group had worsening stress and urge UI sx


Drug Treatment of Overactive BladderDrug Treatment of Overactive Bladder

• Anticholinergic Drugs are mainstay– Oxybutynin IR 2.5-5 mg bid-qid – Ditropan XL 5-20 mg daily– Oxytrol patch TDS 3.9 mg 2x/wk – Tolterodine tartrate IR 1-2 mg bid– Detrol LA 2-4 mg daily

New Drugs:– Trospium chloride (Sanctura) 20 mg bid– Darifenicin (Enablex) 7.5-15 mg daily– Solefenicin (Vesicare) 5-10 mg daily


Muscarinic ReceptorsMuscarinic Receptors

• M1 – Brain (cortex, hippocampus), salivary• glands, sympathetic ganglia

• M2 – Heart, hindbrain, smooth muscle (80% of detrusor)

• M3 – Smooth muscle (20% of detrusor), salivary glands, brain, eye (lens, iris)

• M4 – Brain (forebrain, striatum)

• M5 – Brain (substantia nigra), eye


Hepatic metabolismHepatic metabolism• Oxybutynin CYP 3A4

• Tolterodine CYP 3A4, CYP 2D6

• Darifenacin CYP 3A4, CYP 2D6

• Solifenacin CYP 3A4

• CYP 3A4: Interactions with macrolides, ketoconazole, nefazadone

• CYP 2D6: interactions with TCAs, fluoxetine


Behavioral vs Drug Rx for Urge UI in Older Behavioral vs Drug Rx for Urge UI in Older WomenWomen

• Randomized, controlled trial by Burgio et al JAMA 1998; 280; 1995-2000

• 197 women aged 55-92

• 8 weeks of BFB, 8 weeks of oxybutynin

• 2.5 to 5 mg qd to tid, or placebo control

• All 3 groups reduced UI frequency

• Effectiveness: BFB>drug>placebo


Burgio et al JAMA 1998; 280:1995-2000

0

2

4

6

8

10

12

14

16

Leaks per

week

Behavioral Control

Pre

Post


OxybutyninOxybutynin

• Both anticholinergic and smooth muscle relaxant properties

• 6/7 RCTs show benefit

• 15-58% greater reduction in urge UI than placebo

• Dose: 2.5 -5 mg qd-qid, 20 mg/d maximum


Oxybutynin Controlled ReleaseOxybutynin Controlled Release

• Once daily dosing

• RCT showed rate of daytime continence similar to that for immediate release (53 vs 58%)

• Lower rate of dry mouth than immediate release form


Tolterodine tartrateTolterodine tartrate

• Pure muscarinic receptor antagonist

• Dry mouth most common side effect

• 3 RCT compared tolterodine (2 mg bid) to oxybutynin (5 mg tid): Equally effective and superior to placebo

• Decreased urge U(I in study of 293 pts:47% tolterodine, 71% oxybutynin, 19% placebo, dry mouth 86% oxybutynin, 50% tolerodine


OBJECT StudyOBJECT Study

• Compared efficacy and tolerability of extended release oxybutynin and tolterodine tartrate

• 12 weeks

• Prospective randomized,double-blind, parallel group study

• 276 women and 56 men

• Oxybutynin more effective for weekly urge UI, total incontinence, and urinary frequency

Appel et al Mayo Clin Proc 2001:76


TrospiumTrospium• Dose 20 mg bid

• Renal metabolism

• Nonselective for muscarinic receptors

• Effective for detrusor overactivity in placebo-controlled double-blind studies:

• Trospium 20 mg bid vs tolterodine 2 mg bid in 232 pts reduced voiding frequency and number of UI episodes

• Dry mouth 7% and 9% respectively


DarifenicinDarifenicin• Dose 7.5 to 15 mg daily

• Selective M3 receptor antagonist

• Several RCTs

• Mundy et al 2001 Randomized double-blind trial compared darifenacin 15 mg and 30 mg to oxybutynin 5 mg tid in 25 pts , similar efficacy

• Side effects: Dry mouth, constipation(<2%)


SolefenacinSolefenacin

• Dose 5 to 10 mg daily

• Long acting muscarinic receptor antagonist, selective for M3

• Undergoes hepatic metabolism involving cytochrom P450

• Several multinational trials with over 800 pts, vs placebo, showed efficacy low side effects (2% dry mouth)


DesmopressinDesmopressin

• Decreases urine production

• Helps nocturia

• Dose: 20-40 mcg intranasal spray q hs

• Double-blind crossover trial showed decreased nighttime voids vs placebo, 1.9 vs 2.6

• Contraindications: CHF, HTN, ASCVD


Functional Electrical StimulationFunctional Electrical Stimulation• Frequency of 10-50 Hertz for 15-20 minutes daily

• RCT: 50% cured after 8 weeks compared to sham controls

• 52-77% symptomatic improvement in short-term studies, non RCT

• Implantable electrodes at S2-3, 76% improvement for refractory urge UI x 18 mo

• BUT 33% required surgical revision


Surgery for Urge/OABSurgery for Urge/OAB

• If behavioral and pharmacological treatments don’t work

• Augmentation enterocystoplasty

• One series of 267 patients had a 93% continence rate with 3 yr f/u

• Complications: urinary retention, stones, small bowel obstruction, reservoir rupture


Treatment of Overflow UI Due to Mild BPHTreatment of Overflow UI Due to Mild BPH

• Alpha adrenergic antagonists

– Possibly relaxes prostate smooth muscle and stroma and urethra smooth muscle to increase urine flow

– Tamsulosin, doxazosin, terazosin

– Tamsulosin trials: 53 weeks, 31% and 36% improvement in maximal flow rate with 0.4mg and 0.8 mg/day vs 21% placebo

– Uroselective alfuzosin in late stage clinical trials


Drug Treatment of Mild BPHDrug Treatment of Mild BPH

• Type II 5 alpha reductase inhibitor– Results in atrophy of the prostatic glandular

epithelium due to decreased synthesis of dihydrotestosterone

– Slow onset, 20-30% reduction in prostate volume and LUTS over time

– Side effects: Ejaculatory dysfunction (8%), loss of libido (10%), erectile dysfunction (16%)

– Finasteride , Dutasteride


SummarySummary

• Behavioral treatment is effective for treating stress and urge UI and OAB

• Drugs are effective for treating urge UI and OAB and mild BPH

• New selective agents for urge and OAB based on new understanding of bladder and urethral function

• Caution needed in dosing, especially in older patients

Urinary Incontinence

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