Jan Busby-Whitehead, MD
Chief, Division of Geriatric Medicine
University of North Carolina
Definition of Urinary Incontinence
*
The International Continence Society
University of North Carolina School of Medicine Center for Aging and Health
URINARY INCONTINENCE
Common
Treatable
Significant Effect on
Quality of Life (QoL)
University of North Carolina School of Medicine Center for Aging and Health
Prevalence
• Community: 17% older men, up to 30% older
women
• Hospital: up to 50% older men and women
• LTCF: 50-70% older men and women
University of North Carolina School of Medicine Center for Aging and Health
Hunskaar, et.al., Int Urogynecol J, 2000
University of North Carolina School of Medicine Center for Aging and Health
Hunskaar, et.al., Int Urogynecol J, 2000
University of North Carolina School of Medicine Center for Aging and Health
Reversible causes of UI
D
- Restricted mobility
R
- Infection, impaction
I
- Polyuria
P
- Delirium or Drugs
University of North Carolina School of Medicine Center for Aging and Health
Polyuria,
frequency,
urgency
Alcohol
Caffeine
Diuretics
Urinary
retention
Anticholinergics
Alpha
adrenergic
agonists
Beta
adrenergic
agonists
Calcium
channel
blockers
University of North Carolina School of Medicine Center for Aging and Health
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
University of North Carolina School of Medicine Center for Aging and Health
Physiology
University of North Carolina School of Medicine Center for Aging and Health
Aging Changes
• Decreased bladder capacity
• Reduced voiding volume
• Reduced flow rates
• Increased urine production at night
* Nordling, J Experimental Gerontology, 2002, 37:991
University of North Carolina School of Medicine Center for Aging and Health
Stress
Overflow
CAUSES OF
PERSISTANT
UI
Urge/OAB
Functional
University of North Carolina School of Medicine Center for Aging and Health
Stress UI
Abrams P et al. Urology. 2003;61:37-49.
The complaint of
involuntary
leakage with effort
or exertion or on
sneezing or
coughing
Sudden increase in
abdominal pressure
Urethral pressure
University of North Carolina School of Medicine Center for Aging and Health
Urge UI
Abrams 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
University of North Carolina School of Medicine Center for Aging and Health
Overactive bladder
• Includes urinary urgency with or without
urge incontinence, urinary frequency,
and nocturia
• Associated with involuntary contractions
of the detrusor muscle
University of North Carolina School of Medicine Center for Aging and Health
Mixed UI
Abrams P et al. Urology. 2003;61:37-49. Chaliha C et al. Urology. 2004;63:51-57.
The complaint
of involuntary
leakage
associated with
urgency and
also with
exertion, effort,
sneezing,
or coughing
Sudden increase in
abdominal pressure
Involuntary detrusor
contractions
Urethral pressure
University of North Carolina School of Medicine Center for Aging and Health
Overflow
•Urethral blockage
•The Bladder is not able
to empty properly
Neurogenic/Atonic
Obstruction
University of North Carolina School of Medicine Center for Aging and Health
Functional Incontinence
• Immobility
• Diminished vision
• Aphasia
• Environment
• Psychological
University of North Carolina School of Medicine Center for Aging and Health
Clinical 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?
University of North Carolina School of Medicine Center for Aging and Health
Office 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
University of North Carolina School of Medicine Center for Aging and Health
Basic 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
University of North Carolina School of Medicine Center for Aging and Health
Referral 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
University of North Carolina School of Medicine Center for Aging and Health
Cystometry
• 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
University of North Carolina School of Medicine Center for Aging and Health
Treatment Options
• Behavioral
• Pharmacological
• Functional Electrical Stimulation
• Surgery
University of North Carolina School of Medicine Center for Aging and Health
Are behavioral techniques effective?
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
University of North Carolina School of Medicine Center for Aging and Health
BEHAVIORAL
TREATMENTS
FOR UI
Self
management
techniques
Timed or
scheduled
voiding
Pelvic floor
muscle
exercise with
or without
biofeedback
University of North Carolina School of Medicine Center for Aging and Health
Self Management
• Fluid Intake
– Don’t reduce amount
– Do not drink fluids 2 hr before bedtime
– Avoid: caffeine, alcohol, nicotine
University of North Carolina School of Medicine Center for Aging and Health
Scheduled 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
University of North Carolina School of Medicine Center for Aging and Health
Pelvic 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
University of North Carolina School of Medicine Center for Aging and Health
100
PMFE Without
Biofeedback
90
80
PMFE With
98%
Biofeedback
91%
70
60
50
40
50%
30
38%
20
10
0
Range of Improvement
Range of Improvement
University of North Carolina School of Medicine Center for Aging and Health
Randomized Trials of Behavioral Treatment
for 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
University of North Carolina School of Medicine Center for Aging and Health
Behavioral 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
University of North Carolina School of Medicine Center for Aging and Health
Limitations of Behavioral Treatment
Studies
• 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
University of North Carolina School of Medicine Center for Aging and Health
NIH Treatment Trial
Kincade, Dougherty, Busby-Whitehead
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
University of North Carolina School of Medicine Center for Aging and Health
Drug Treatment for UI: What Works
• Stress UI
–
Alpha adrenergic agents?
–
Estrogen?
–
Combination therapy?
University of North Carolina School of Medicine Center for Aging and Health
Alpha 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
University of North Carolina School of Medicine Center for Aging and Health
Duloxetine
(Cymbalta)
• FDA application for stress UI withdrawn
• Warning for liver dysfunction, alcohol
University of North Carolina School of Medicine Center for Aging and Health
Estrogen
• 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
University of North Carolina School of Medicine Center for Aging and Health
Drug 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
University of North Carolina School of Medicine Center for Aging and Health
Muscarinic 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
University of North Carolina School of Medicine Center for Aging and Health
Hepatic 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
University of North Carolina School of Medicine Center for Aging and Health
Behavioral vs Drug Rx for Urge UI in Older
Women
• 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
University of North Carolina School of Medicine Center for Aging and Health
Burgio et al JAMA 1998; 280:1995-2000
16
14
12
10
Leaks per
8
week
6
Pre
Post
4
2
0
Behavioral
Control
University of North Carolina School of Medicine Center for Aging and Health
Oxybutynin
• 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
University of North Carolina School of Medicine Center for Aging and Health
Oxybutynin 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
University of North Carolina School of Medicine Center for Aging and Health
Tolterodine 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
University of North Carolina School of Medicine Center for Aging and Health
OBJECT Study
Appel et al Mayo Clin Proc 2001:76
• 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
University of North Carolina School of Medicine Center for Aging and Health
Trospium
• Dose 20 mg bid
• Renal metabolism
• Nonselective for muscarinic receptors
• Effective for detrusor overactivity in placebocontrolled 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
University of North Carolina School of Medicine Center for Aging and Health
Darifenicin
• 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%)
University of North Carolina School of Medicine Center for Aging and Health
Solefenacin
• 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)
University of North Carolina School of Medicine Center for Aging and Health
Urinary
retention
Gastric
retention
Cardiac
arrhythmias
Contraindications
for
Anticholinergics
Bladder
outlet
obstruction
Narrow
angle
glaucoma
University of North Carolina School of Medicine Center for Aging and Health
Desmopressin
• 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
University of North Carolina School of Medicine Center for Aging and Health
Functional 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
University of North Carolina School of Medicine Center for Aging and Health
Surgery 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
University of North Carolina School of Medicine Center for Aging and Health
Treatment 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
University of North Carolina School of Medicine Center for Aging and Health
Drug 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
University of North Carolina School of Medicine Center for Aging and Health
Summary
• 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
University of North Carolina School of Medicine Center for Aging and Health