Management of Overactive Bladder

Dee E. Fenner, M.D.Chair and Furlong Professor of Women’s HealthDept. of Obstetrics and GynecologyUniversity of Michigan

deef@umich.edu

Disclosures

• NONE

Objectives

• Review treatment options for Urge Urinary Incontinence• Behavioral • Physical therapy of the pelvic floor• Medications• Procedures

Stress urinary incontinence• “I leak when I laugh, cough,

or sneeze”• Definition: Loss of urine

involuntarily with effort or physical exertion

• Etiology thought to relate to urethral integrity• Does not result from a

cystocele

All that leaks isn’t stress…• Overactive bladder syndrome: 17% women

• Frequency: micturition occurs more frequently during waking hours than previously deemed normal by the woman (>7 voids)

• Urgency: sudden, compelling desire to pass urine that is difficult to defer

• Urgency urinary incontinence – prevalence 7-33%• Complaint of involuntary loss of urine associated

with urgency• Women > men

Bladder controlling

UUI treatment overview• Behavioral changes

• Timed voiding ~3hrs• Decrease fluids and bladder irritants• Manage constipation

• Medications• Anticholinergics• Beta-3 blockers

• Pelvic floor physical therapy• Weight loss• Neuromodulation

• Interstim• PTNS• Traditional acupuncture

• Botox intra-detrusor injections

Equilibration

UUI practical tips• Use only incontinence pads, not menstrual

• Never Always®• Maybe cotton pads (available online/Amazon,

health stores)• If itching/pain/bleeding, needs pelvic exam

• Set an alarm in the middle of night before urgency wakes you

• Stop drinking ~7pm• Compression stockings/elevation in daytime

• If lower extremity edema and nocturia

UUI practical tips• Vaginal estrogen

• Some evidence to suggest it treats OAB as well as Detrol

• Reduction of UTIs• Least systemic absorption: generic = Yuvafem• Least patient effort: Estring (no generic)

“I don’t drink enough”• Numerous smart phone

apps exist to promote ‘hydration’• MyWater• Water Your Body• Water Tracker• Replenish Your Body• DrinkMore

Lack of scientific support• No scientific studies support 8x8 (eight 8oz glasses of water a day)

• Other beverages (caffeinated, alcoholic) do count• Fluid is found in foods• Sophisticated osmoregulatory system maintains balance

• Encourage drinking:• People who exercise regularly• Warm, humid temperatures• Elderly (in moderation)• Certain medical conditions (ie, profuse diarrhea)

• We advise using urine color as assessment of hydration• Want a pale yellow color (not clear, not dark)

Bladder irritants• Urgency and frequency symptoms are common• One treatment is modification of intake of

“potentially irritating beverages” (PIBs)• Anecdotally successful• Sparse evidence supporting

• Potentially Irritating Beverages (PIBs) defined as:

caffeinated artificially sweetened

citric/acidic juices

alcoholic

carbonated

Bladder irritants• Copious recommendations in lay media encourage women to

reduce caffeinated, carbonated, acidic drinks and fluids in general

• In favor of:

• Show me the data … ?

PIBs and real life• When women were asked to completely eliminate irritating

beverages (PIBs) without decreasing total intake volume:• Decreased overactive bladder symptoms • Variable volume of total beverage intake• Incomplete PIB elimination (some increase!)

• Key Question:

PIBs or Volume?

Parallel-group RCT with three-period fixed sequence

Answered ad for symptoms of urgency/frequency

Screening: ≥16oz PIBs and ≥32oz total

Randomized n=61

Control (healthy diet guidelines)n=31

2 weeks later: 3-day voiding diary

2 months after baseline:3-day voiding diary

Baseline 3-day voiding diary

N=1 lost to follow-up

N=2 lost to follow-up

Leakage was not required

PIBs Educationn=30

PIB replacement and caffeine reduction

Results• Despite detailed instruction to maintain fluid

intake volume, both groups reduced total beverage intake by about 7oz per day

• No significant difference between groups

Results

Results: Frequency

Results: Bother

Results: Effects of specific PIBs• Looking at bother score:

• Reduction in artificial sweeteners (p=0.04) and caffeinated beverages (p=0.004) predicted improvement in bother

• Looking at voids per day: • Reduction in alcoholic beverages (p=0.04) and caffeinated

beverages (trend only, p=0.06) predicted improvement in frequency

• J Urol Nov 2017 Systematic Review – sparse evidence• Association between increased fluid, caffeine and

urgency/frequency

Conclusions & Take-aways• What’s new:

• SUI: non-collagen bulking injections, hypopressive PT• UUI: Botox, PTNS, mirabegron, hypopressive PT

• What’s old:• SUI: mesh slings, pessaries (oldies but goodies!)• UUI: anticholinergics, esp. short-acting (oldie but not-goodie)

• What’s fizzy:• SUI: Minislings (will fizz out…)• UUI: Stick with carbonated water flavored with fruit!

• Avoid caffeine, alcohol, and artificial sweeteners

mschimpf@umich.edu

Pelvic Floor Physical Therapy• First line treatment• More effective for OAB than SUI• Graduated muscle training

• 3 sets of ten contractions a day• Short contraction (flicker) with increasing time of

contraction• Associate with activity – eating, TV news, stop light,

• Transfer ability to squeeze to activity – walking to toilet• Squeeze before standing to suppress urge

Meds: Anticholinergics• Muscarinic receptor antagonists

• In US: oxybutynin, tolterodine, fesoterodine, trospium, solifenacin, and darifenacin

• Increase bladder capacity• Decrease urgency• Side effects: Dry eye, Dry mouth, Constipation

• Newer meds target M3 receptors “specific” to bladder to minimize • Not really successful

• Avoid if wide-angle glaucoma, frail elderly

Meds: Anticholinergics• Muscarinic receptor antagonists

• ~40% better than placebo – but placebo ~30% better than nothing

• Use extended-release formulations rather than short-acting• OTC patch available now

• Expensive and rarely make you 100% dry• Most people are no longer on a drug past 1st

prescription, very few by 12mo later (as high as 90% discontinue)

Cognitive side effects• Long known to be anticholinergic side effect, but thought to

be reversible/transient• Newer data show cumulative clinical decline, irreversible risk

of dementia and brain atrophy:• Compared to 350 patients not using anticholinergics, 52

anticholinergic-using patients (mean 73.3 yrs) showed: • Lower mean scores on Weschler Memory Scale-Revised Logical

Memory Immediate Recall • Lower mean scores on Trail Making Test Part B • Lower executive function composite score • Reduced total cortical volume and temporal lobe cortical thickness • Greater lateral ventricle and inferior lateral ventricle volumes

• 1. Gray et al. JAMA Intern Med. 2015 Mar;175(3):401-7.• 2. Risacher SL et al. JAMA Neurol. 2016 Jun;73(6):721-32.

• Behavioral therapies first• Providers should counsel on the associated risk of cognitive

impairment, dementia, and Alzheimer disease, prescribe the lowest effective dose, and consider alternative medications in patients at risk

• Be aware of other anticholinergics patients are also using• Refer for Botox or neuromodulation

Meds: Newest option• ß-3-adrenoreceptor agonists (mirabegron)

• 1st new option in 30 yrs• Enhancing storage function and relaxing the

urinary bladder – ß3 receptors play a role in detrusor relaxation• Effective vs placebo in studies• Improves daily incontinence episodes, nocturia,

number of daily voids, and urine volume per void

• Caution in patients with uncontrolled hypertension, frail elderly

Obesity and UI

• Each 5-unit increase in body mass index above normal weight is associated with a 40% to 70% increased odds of prevalent incontinence and a 30% to 60% increased risk of incident incontinence

• The prevalence of incontinence has been reported to be as high as 60% to 70% among severely obese women.

Brown JS, Obstet Gynecol. 1996;:715–721. Burgio KL.. Obstet Gynecol. 2007; 110(5):1034–1040.

Weight loss and OAB• 338 women randomized for a 6 month trial

• Mean BMI 36• 24±18 (case) and 24±16 (control) UI episodes/week• mean weight loss of 8.0% (7.8 kg) case vs. 1.6% (1.5

kg) control • 47% vs. 28% reduction in UI episodes • 70% of women in control group saw clinical relevant

reduction in UI

Subak N Engl J Med. 2009; 29; 360(5): 481–490

Urinary Incontinence before and after Bariatric Surgery

Subak JAMA Intern Med. 2015; 175(8): 1378–1387

Posterior Tibial Nerve Stimulation (PTNS)

• Initially discovered as part of transcutaneous patch tibial nerve stimulation (McGuire et al, J Urol 121:78-9, 1983)

• Stoller investigated direct stimulation since it is a terminal projection of S3

• Technique involves 34 G needle placement in office 3-4 cm above medial malleolus and ground pad on same foot near arch

• Connect lead to stimulator

PTNS• Spleen-6 acupuncture

point

Posterior Tibial Nerve Stimulation (PTNS)• Stimulator has adjustable pulse intensity (0-9mA)• Fixed pulse width of 200 ųs• Frequency of 20 Hz• Amplitude slowly increased till large toe curls• 12 weekly sessions for 30 min each• Responses usually in 5-6 sessions and if improved

after 12 sessions, begin chronic rx

Neuromodulation: PTNS• 12 weekly visits about 30 min each then monthly maintenance• Acupuncture-style needle placed posterior to medial malleolus

• Stimulate posterior tibial nerve peripherally • Modulate sacral nerve plexus through S2-4 nerves

• RCT: 80% patients improved/cured vs. 55% patients on Detrol • More efficacious than pelvic floor muscle training exercises

and behavioral therapy for improving: urgency, urinary incontinence episodes, daily voids, volume per void, and QOL

Neuromodulation: Interstim• Electrode placed at S3 nerve foramen

• Two-step surgical procedure• Battery lasts 5 yrs

• Systematic review: 67-80% patients achieve continence or >50% improvement

• Now also indicated for fecal incontinence• Cannot have MRIs afterward

Interstim

Sacral Neuromodulation• May help OAB based on “reprogramming” of

sacral afferent fibers• FDA approved in 1997• Indications:

• Refractory urge-frequency• Urge incontinence• Idiopathic non obstructive urinary retention

• 2 stage procedure or PNE

Idiopathic Sacral Neuromodulation Data

Study Study Design

Sample Size

Follow Up(months)

Success%

Weil, Eur Urol2000

RCT 21 6 56%

Schmidt, J Urol 1999

RCT 34 6 75%

Bosch, J Urol 2000

Open label 40 47 60%

Hassouna J Urol 2000

RCT 25 6 56%

Amundsen Am J Obst

Open label 12 7 100%

Van Voskullen BJU int 2007

Open label 31 15.5 90%

Greonendijk BJU int 2008

Open label 67 6 61%

Botox• FDA approved for urgency UI/OAB in

Jan 2013• Injected into detrusor at bladder

base during cystoscopy, relaxes muscle

• Systematic review of 23 trials: 3.9 fewer leaks per day

• Significant QOL improvements• Risks:

• Retention – temporary (risk ~9% with 100U injection)

• UTIs• Presently third-line treatment• Ideal dosing still being defined

Botulinum ToxinContraindications

Infection at injection siteHypersensitivity

Issues:Complex with human albuminInteraction with aminoglycosides

Immunogenicity: 2 % of patients develop antibodies to botulinum

Complications:Localized pain, tenderness, or bruising at inj. siteWeakness of adjacent muscle due to spread of toxinNo reported complications with GU applications

Botox A for Idiopathic OABStudy Design Sample

SizeSuccess Success

%Kessler,

NUU 2005Open label 11 3 months 91%

Popat, J Urol 2005

Open label 44 4 months 57%

WernerAm J Obst,

2005

Open label 26 9 months 65%

BrubakerJ Urol 2008

RCT 43 (28 botox, 15 placebo)

373 days 60% PGII

Botox or drugs?• ABC trial (Visco et al)

• Blinded RCT of women with idiopathic urgency urinary incontinence• Daily solifenacin 5-10mg or trospium XR 60mg + placebo injection• One injection of 100U onabotulinumtoxin A + placebo pills

• Successful treatment• Baseline 5.0 leaks/day to 3.4/day in med group vs 3.3 in Botox (NS)• Resolution of incontinence in 13% med group vs 27% Botox (p =

0.003)• QOL improved equally

• Side effects: • Med group had more dry mouth• Botox group more catheterization (5% at 2mo) and UTIs (33%)

• Systematic review of Botox vs any drug (BJU July 2107)• Botox patients had greatest reductions in leaks, urgency, and frequency

• Botox vs Interstim: same symptom relief, pts. preferred Botox• Higher rate UTIs with Botox

UUI treatment overview• Behavioral changes

• Timed voiding ~3hrs• Decrease fluids and bladder irritants• Manage constipation

• Medications• Anticholinergics• Beta-3 blockers

• Pelvic floor physical therapy• Weight loss• Neuromodulation

• Interstim• PTNS• Traditional acupuncture

• Botox intra-detrusor injections

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