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Water, Water Everywhere:
Update on Urinary Incontinence
Jan Busby-Whitehead, MD
Chief, Division of Geriatric Medicine
University of North Carolina
Objectives
1. Understand the pathophysiologic causes of urinary
incontinence
2. Understand how to do a clinic evaluation of urinary
incontinence
3. Describe nonpharmacologic treatments for urinary
incontinence
4. Discuss pharmacologic treatments for urinary
incontinence
Case Summaries
• 73 y/o woman with hypertension complains that the
slight urine leakage she has had for >20 yr is
worse during her daily mile walk
• 76 y/o obese woman with mild dementia living in
nursing home, is wet during day and night
• 80 y/o man has postvoid dribbling, nocturia, and
decreased urinary stream
Definition of Urinary Incontinence
The International Continence Society
Urinary Incontinence
Common
Treatable
Significant Effect on
Quality of Life (QoL)
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
Reversible causes of UI
D
- Restricted mobility
R
- Infection, impaction
I
- Polyuria
P
- Delirium or Drugs
Drugs Contributing to UI
Polyuria, Frequency, Urgency
Alcohol
Caffeine
Diuretics
Urinary Retention
Anticholinergics
Alpha
adrenergic
agonists
Beta
adrenergic
agonists
Calcium
channel
blockers
Bladder Anatomy
Hollow, distensible, muscular organ

Reservoir of urine
•
•
•

Capacity ~600 mL
Desire ~200 mL
Normal void ~300 mL
Organ of excretion
•
•
•
•
Behind symphysis pubis
Female – against anterior
Trigone
Sphincter
wall of uterus
Innervation of the Lower Urinary Tract (LUT)
Abram P et al. The Overactive Bladder: A Widespread and Treatable Condition. 1998.
Aging Changes
• Decreased bladder capacity
• Reduced voiding volume
• Reduced flow rates
• Increased urine production
at night
Nordling, J Experimental Gerontology, 2002, 37:991.
Stress 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 UI
The complaint of involuntary leakage accompanied by or
immediately preceded by urgency
Involuntary detrusor
contractions
Urethral pressure
Abrams P et al. Urology. 2003;61:37-49.
Ouslander J. N Engl J Med. 2004;350(8):786-799.
Overactive Bladder
• Includes urinary urgency with or
without urge incontinence, urinary
frequency, and nocturia
• Associated with involuntary
contractions of the detrusor
muscle
Overflow
•Urethral blockage
Neurogenic/Atonic
•The bladder is not able to
empty properly
Obstruction
Functional Incontinence
• Immobility
• Diminished vision
• Aphasia
• Environment
• Psychological
http://foxvalleyphysicaltherapy.com
Office Assessment 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
Screening Questions
• Do you ever leak urine/water when you don’t
want to?
• Do you ever leak urine/water when you cough,
laugh or exercise?
• Do you ever leak urine/water when on the way
to the bathroom?
Clemens, 2012 Up to Date
Basic Evaluation of UI
• History: Bladder diary
• Physical examination, especially
Genitourinary and Neurological
• Bladder stress test
• Postvoid residual
http://www.erpocketbooks.com/er-ultrasounds/trauma-ultrasounds-from-the-ed/
• Urinalysis, urine culture if indicated
• BUN, creatinine, fasting glucose
Referral Criteria



Recurrent urinary tract infections

Recent gynecological or urological surgery
or pelvic radiation

Failed treatment of stress or urge UI
Hematuria
Elevated postvoid residual or other evidence of
possible obstruction
http://www.real-estate-marketing-link.info/referral_partners.html
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
http://bladder-health.net/urodynamic-testing.htm
Treatment Options
• Behavioral
• Pharmacological
• Electrical stimulation
• Surgery
Behavioral Treatment Options
• Self management techniques
• Timed or scheduled voiding
• Pelvic floor muscle exercise with or without
biofeedback
Fluid Intake
• Fluid Intake
• Don’t reduce amount (up to 2 L/d)
• Do not drink fluids 2 hr before bedtime
• Avoid: caffeine, alcohol, nicotine
Weight Loss
• Randomized trial of 338 women, mean
BMI 36 kg/m²
• 6 month weight loss vs. education
• Weight loss 8% vs. 1.6%
• 47% vs. 28%
in stress but not urge UI
NEJM 2009; 360:481
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
Pelvic Muscle Exercises (Kegels)
• Isolation of the pelvic muscles
• Avoidance of abdominal, buttock or thigh muscle
contractions
• Ability to hold contraction 10 seconds, repeat in groups of
10-30 TID
• 3 sets of 8 to 12 slow velocity contractions sustained for up
to 10 seconds, 3-4 times weekly for at least 4 to 6 months
Obstet Gynecol Survey 1992; 47:322.
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
Cochrane Collaboration 2011
Efficacy of PMFE Treatment for Stress UI
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
Behavioral vs. Drug Rx for Urge UI
in Older Women
• Randomized, controlled trial of 197 women aged 5592
• 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
Oxybutynin vs Behavioral Treatment for Urge UI
16
14
12
10
Leaks per
8
week
6
Pre
Post
4
2
0
Behavioral
Control
Burgio et al JAMA 1998; 280:1995-2000
Are Behavioral Techniques Effective?
• For treatment of stress, urge UI, mixed UI,
but generally do not cure
• For community dwelling men and women
• For cognitively intact, motivated persons
Drug Treatment for UI: What Works
• Stress UI
–
Alpha adrenergic agents?
–
Ceratonin reuptake inhibitors?
–
Estrogen?
–
Combination therapy?
Alpha Adrenergic Drugs
• Stimulate urethral smooth muscle contraction
• Phenylpropanoloamine
–
–
Once a first line drug
WITHDRAWN FROM MARKET due to report of
hemorrhagic stroke
Duloxetine (Cymbalta)
• Serotonin and nonepinephrine reuptake inhibitor
• FDA approved for major depression and neuropathic pain
• European Union approved for stress UI
• Warning for liver dysfunction, alcohol
• Nausea common
• In RCTs, 40mg BID resulted in 50% - 54% decrease in UI
frequency vs. 27% - 40% with placebo
J Urol 2003; 170:1
BJU Int 2004; 93:3
Estrogen
• 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
Obstet Gynecol 2001; 97:116
Estrogen
• Women’s Health Initiative 2005: 23,296 women age 5079
– Randomized to conjugated estrogen or conjugated estrogen
plus medroxyprogesterone acetate or placebo
– Continent women treated with estrogen plus
medroxyprogesterone acetate had increased risk of all types UI
at 1 year
– Incontinent women treated with hormones had worsening UI
JAMA 2005; 293:935.
Topical Estrogen
• May improve UI per meta-analysis of small randomized
trials
Cochrane Database Sept Rev 2009.
• Estradiol vaginal cream 0.01%, 2 to 4g daily x 1-2 weeks,
taper to 1 to 2g daily x 1-2 weeks then 1g three times per
week, re-evaluate at 3 months
UptoDate 2011
Drug Treatment for Urge UI/OAB
• Anticholinergic drugs with antimuscarinic effects are
mainstay
• Increase bladder capacity and decrease urgency
• 40% higher rate of cure or improvement vs. placebo
• Efficacy increases up to 4 weeks
DuBeau, Up to Date 2011
Drug Treatment of Urge UI/OAB
• Anticholinergic Drugs
–
–
–
–
–
●
Oxybutynin (Ditropan) IR 2.5-5 mg bid-qid
Oxybutynin (Ditropan) XL 5-20 mg daily
Oxybutynin (Oxytrol) patch TDS 3.9 mg 2x/wk
Tolterodine tartrate (Detrol) IR 1-2 mg bid
Tolterodine tartrate (Detrol) LA 2-4 mg daily
Newer Drugs
–
–
–
–
Trospium chloride (Sanctura) 20 mg qd- bid
Fesoterodine (Toviaz) 4-8 mg daily
Darifenicin (Enablex) 7.5-15 mg daily
Solefenicin (Vesicare) 5-10 mg daily
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 fluoxetine, Tricyclic antidepressants
Oxybutynin
• Dose:
– 2.5 -5 mg qd-qid, 20 mg daily maximum IR
– 5 mg qd, 20-30 mg daily maximum ER
– 3.9 mg patch changed 2x per week
– 10% topical gel (1 gram) applied daily
• Both anticholinergic and smooth muscle relaxant properties
• 6/7 RCTs show benefit
• 15% - 58% greater reduction in urge UI than placebo
• IR, ER, transdermal patch, topical gel, all similar efficacy
DuBeau, Up to Date 2011
Fesoterodine
• Dose: 4-8 mg ER
• Non-hepatically metabolized to active metabolite of
toloterodine
• In a 12 week randomized trial of 883 patients with
overactive bladder on 4 or 8 mg daily had small to
moderate decrease in total voids and UI episodes vs.
placebo
• Adverse effects: dry mouth 26%; constipation 11%
Tolterodine Tartrate
• Dose 1-2 mg bid IR
• Pure muscarinic receptor antagonist
• 3 RCT compared tolterodine (2 mg bid) to oxybutynin
(5 mg tid): Equally effective and superior to placebo
• Decreased urge UI in study of 293 pts: 47% tolterodine,
71% oxybutynin, 19% placebo, dry mouth 86% oxybutynin,
50% tolterodine
• Case reports of cognitive effects mimicking dementia
OBJECT 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
Trospium
• Dose 20 mg bid IR, 60 mg daily ER
• Only antimuscarinic renally cleared
• Nonselective for muscarinic receptors
• Effective for detrusor overactivity in placebo-controlled doubleblind 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
• Take on an empty stomach
Darifenicin
• Dose 7.5 to 15 mg daily
• Selective M3 receptor antagonist
• 12 week randomized trial in 445 adults, mean UI episodes
per week decreased more with darifenicin 15 mg vs.
placebo (12.6-9.8)
• 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%)
Int J Clin Pract 2006; 60:119.
Solefenacin
• Dose: 5 to 10 mg daily
• Selective M3 receptor antagonist
• 12 week randomized trial of 1200 adults, 5 mg
titrated to 10 mg decreased UI episodes vs. 4 mg
tolterodine
• Several multinational trials with over 800 patients
vs. placebo showed efficacy, low side effects (2%
dry mouth)
Eur Urol 2005; 48:464.
Distribution of Cholinergic
and Adrenergic Receptors
• Human bladder smooth muscle
contains primarily M2 (66%) and
M3 (33%) subtypes
• Activation of M3 receptors is primary
stimulus for bladder contraction
• Stimulation of M2 receptors may
cause contractions
• M2 receptors may have a more
important functional role in the
pathologic bladder
Andersson KE. Lancet Neurol. 2004;3:46-53.
Braverman A et al. Urology. 2001;165:36.
Braverman AS et al. Urology. 2002;167:43.
Anticholinergics
• Systematic review of 86 randomized trials and metaanalysis of 70 trials in patients with urge UI
– Tolterodine better tolerated than Oxybutynin but similar
efficacy
– Fesoterodine better efficacy than Tolterodine ER but more
dry mouth
– Solifenacin more effective and better tolerated than
Tolterodine IR
Urinary
retention
Gastric
retention
Cardiac
arrhythmias
Contraindications
for
Anticholinergics
Bladder
outlet
obstruction
Narrow
angle
glaucoma
Drug Treatment of UI in Cognitively Impaired Patients
• Randomized trial of 75 NH residents with urge UI who failed
prompted voiding, Oxybutynin IR improved number of wet checks
(40% vs. 18%) but not overall UI frequency
J Am Geriatr Soc 1995; 43:610
• Randomized trial of 50 NH residents; Oxybutynin ER 5 mg did not
improve UI
J Am Med Dir Assoc 2011; 12:639
• 4 week randomized study of 12 NH found no difference in cognitive
assessment in patients with dementia receiving Oxybutynin ER 5mg
vs. placebo
J Am Geriatr Soc 2008; 56:862
Treatment of Urge UI in Men
• Start with alpha blocker
• May add low dose antimuscarinic
• One randomized trial of tamsulosin plus tolterodine
more effective in reducing urge UI than placebo
http://phd7.idaho.gov/health%20promotion/Fit%20and%20Fall/fit&fallmain.html
Drug Treatment of Mild BPH
• Alpha adrenergic antagonists
–
Relaxes prostate smooth muscle of prostate and bladder neck
•
•
•
•
•
–
–
Tamsulosin (Flomax) 0.4 -0.8mg daily
Doxazosin (Cardura) 1-2 mg then up to 8 mg daily IR, 4-8 mg ER
Terazosin (Hytrin) 0.5 mg up to 20 mg daily
Alfuzosin (Uroxatrol) 10 mg daily
Silodosin (Rapaflo) 4 mg daily
Tamsulosin trials: 53 weeks, 31% and 36% improvement in maximal
flow rate with 0.4 mg and 0.8 mg/day vs. 21% placebo
Adverse effects: orthostatic hypotension and dizziness, floppy iris
syndrome in cataract surgery patients
Drug Treatment of Mild BPH
• Dose:
•
•
Finasteride (Proscar) 5 mg daily
Dutasteride (Avodart) 0.5 mg daily
• 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%)
Trend for increased risk of more aggressive prostate cancer
Rare reports of breast cancer in men taking finasteride either 1 mg or 5 mg
Electrical Stimulation for Urge UI
• 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
Sacral Nerve Stimulation
• Electrodes placed percutaneously adjacent to the S3 dorsal
roots
• If 50% improvement seen
with a 1-4 week trial, lead
is permanently implanted
• Use for refractory urge UI,
refractory urgency-frequency
and non- obstructive urinary retention
http://www.webmd.com/urinary-incontinence-oab/oab-treatment-11/slideshow-overactive-bladder
• Adverse events: Lead migration, pain, infection,
electrical shock
Botulinum Toxin
• For UI refractory to anticholinergic therapy
• Major limitation: urinary retention
http://www.robertreeveslaw.com/blog/fda-says-botox-cleared-for-management-of-urinary-incontinence-related-to-spinal-cord-injury
http://www.sciencedirect.com/science/article/pii/S0302283803002501
Botulinum Toxin
• 1987 first injection into external sphincter muscle for
bladder-sphincter dyssynergia
• Injected directly into detrusor later and posterior bladder
wall, trigone avoided
• 2005 first randomized placebo controlled study of 59
patients, 200 U, 300 U or placebo over 24 wks
• Mean decrease in UI 50% vs 0; p<.05
• Improved quality of life for treatment
Botulinum Toxin A
• Indication:
– Neurogenic with DI: open label studies, one randomized
controlled trial, one randomized placebo controlled trial
– Overactive bladder: open label studies
Efficacy good
Side effects: local pain, infection, hematuria, retention
Systemic muscle weakness up to 2 mo
Nitti, Rev Urol 2006;8:198
Investigational Drugs
• Serlopitant
– Neurokinin – 1 receptor antagonist
– In randomized trials reduced number of daily voids but not UI
vs. placebo
• Beta-3 agonists in phase II and III trials
• Agent blocking sodium channels and muscarinic
receptors in phase II trials
• Vitamin D3 analogue has completed phase II trials
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
http://www.afrjpaedsurg.org/article.asp?issn=01896725;year=2011;volume=8;issue=1;spage=109;epage=111;aulast=Chatterjee
Desmopressin
• Dose: 20-40 mcg intranasal spray q hs
• Decreases urine production
• Helps nocturia
• Double-blind crossover trial showed decreased
nighttime voids vs. placebo, 1.9 vs. 2.6
• Contraindications: CHF, HTN, ASCVD
• Risk of hyponatremia
Practical Management
• Pad and garments
– www.simonfoundation.org
– www.nafc.org
• Pessaries
– For pelvic organ prolapse or stress UI
• Catheters
– Short-term use
– High morbidity
Case Summaries
• 73 y/o woman with hypertension complains that the
slight urine leakage she has had for >20 yr is
worse during her daily mile walk
• 76 y/o obese woman with mild dementia living in
nursing home, is wet during day and night
• 80 y/o man has postvoid dribbling, nocturia, and
decreased urinary stream
Key Points
• Behavioral treatment is effective for treating stress and urge UI and
OAB
• Anticholinergics are effective for treatment of urge UI and OAB; new
selective agents have fewer side effects
• The main contraindications to anticholinergic drugs are: urinary or
gastric retention, narrow angle glaucoma, arrhythmia, outlet
obstruction
• Alpha adrenergic antagonists and 5 alpha reductase inhibitors are
the primary drugs used for treatment of mild overflow UI from BPH
• Oral estrogen has not been proven to be useful for treatment of
stress or urge UI, but topical estrogen useful for atrophic symptoms