Maturitas 71 (2012) 188 193

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Maturitas

jo ur n al hom ep age : www.elsev ier .com/

Mini review

Overac nt

Dudley RDepartment of

a r t i c l

Article history:Received 3 NoReceived in re15 November Accepted 17 N

Keywords:Overactive blaUrinary incontAntimuscarini

l synd usuan a ctory sretraiptom

neuriew oovera

1. Introdu

Overactisymptom cfrequency and nocturia, with or without urgency urinary incon-tinence, in the absence of urinary tract infection or other obviouspathology [1].

The aim of this review is to provide practical clinical adviceregarding the investigation and management of women complain-ing of lower urinary tract symptoms suggestive of OAB as well asproviding a

2. Prevalen

Epidemiprevalence with age risther prevalprevalence Frequency w54% compla

More renary tract sUnited Kinthe age of of symptom

CorresponE-mail add

symact sn.

3. Pathophysiology

The symptoms of OAB are due to involuntary contractions of thedetrusor muscle during the lling phase of the micturition cycle.These involuntary contractions are termed detrusor overactivity [1]and are mediated by acetylcholine-induced stimulation of bladder

0378-5122/$ doi:10.1016/j.n evidence based approach to treatment.

ce

ological studies from North America have reported aof OAB in women of 16.9% and the prevalence increasesing to 30.9% in those over the age of 65 years [2]. Fur-ence data from Europe [3] also has shown the overallin men and women over the age of 40 years to be 16.6%.as the most commonly reported symptom (85%) whilstined of urgency and 36% urgency incontinence.cently a further population based survey of lower uri-ymptoms in Canada, Germany, Italy, Sweden and thegdom has reported on 19 165 men and women over18 years [4]. Overall 11.8% were found to complains suggestive of OAB and 64.3% reported at least one

ding author. Tel.: +0203 299 9000.ress: dudley.robinson@nhs.net (D. Robinson).

muscarinic receptors [5]. However OAB is not synonymous withdetrusor overactivity as the former is a symptom based diagnosiswhilst the latter is a urodynamic diagnosis. It has been estimatedthat 64% of patients with OAB have urodynamically proven detru-sor overactivity and that 83% of patients with detrusor overactivityhave symptoms suggestive of OAB [6]. Hence the terms are notsynonymous.

4. Clinical presentation

Overactive bladder usually presents with a multiplicity of symp-toms. Those most commonly seen are urgency, daytime frequency,nocturia, urgency incontinence, stress incontinence, nocturnalenuresis and often coital incontinence. However it is important toremember that there are numerous other causes of urgency andfrequency (Table 1).

There are no specic clinical signs in women with overactivebladder but it is always important to look for vulval excoriation,urogenital atrophy, a urinary residual and stress incontinence.Occasionally an underlying neurological lesion such as multiple

see front matter 2011 Published by Elsevier Ireland Ltd.maturitas.2011.11.016tive bladder: Diagnosis and manageme

obinson , Linda CardozoUrogynaecology, Kings College Hospital, London, UK

e i n f o

vember 2011vised form2011ovember 2011

dderinencecs

a b s t r a c t

Overactive bladder (OAB) is a clinicawithout urgency incontinence and isof women may be managed based othose women with complex or refracconservative approach using bladder For those women with persistent symsuch as intravesical Botulinum Toxin,

This review, whilst giving an overvmanaging women with symptoms of

ction

ve bladder (OAB) is the term used to describe theomplex of urinary urgency, usually accompanied by

urinarynary trwomelocate /matur i tas

rome describing the symptom complex of urgency, with orlly associated with frequency and nocturia. Whilst a numberlinical diagnosis alone urodynamic studies may be useful inymptoms. In the rst instance all women will benet from aning although a number will require antimuscarinic therapy.s following medical therapy alternative treatment modalitiesomodulation or reconstructive surgery may be considered.f the syndrome, will focus on a practical clinical approach toctive bladder (OAB).

2011 Published by Elsevier Ireland Ltd.

ptom. Nocturia was the most prevalent lower uri-ymptom being reported by 48.6% of men and 54.5% of

D. Robinson, L. Cardozo / Maturitas 71 (2012) 188 193 189

Table 1Common causes of frequency and urgency of micturition.

UrologicalUrinary tract infectionDetrusor oveSmall-capacInterstitial cChronic urinBladder mucBladder calcUrethral synUrethral divUrethral obsGynaecologPregnancyStress inconCystocoelePelvic mass,Previous pelRadiation cyPostmenopaSexualCoitusSexually tranContraceptivMedicalDiuretic theUpper motoImpaired renCongestive cHypokalaemEndocrineDiabetes meDiabetes insHypothyroidPsychologicaExcessive drHabitAnxiety

sclerosis wS2, 3 and 4

5. Investig

Whilst opatients reqnosis as weurinary trac

5.1. Urine c

A midstrculture and

5.2. Freque

All patieto evaluatenumber of voided ovediurnal and

5.3. Urgenc

Urgencytom of OAdevelopmetinence. Sedeveloped

Table 2Urgency severity scales.

Patient Perception of Intensity of Urgency Score (PPIUS)a

Urgency Perception Score (UPS)b

s Urg

wrighnts P;105:ozo L:591n A, Cry urg4:604

speci

nital dy of lif

Healtinenc

akereasurnairener Tns wi:677[8].an JF

in wom

ay bl pra

uality

lity oractivityity bladderystitisary retention/chronic urinary residualosal lesion, e.g. papillomaulusdromeerticulumtructionical

tinence

e.g. broidsvic surgerystitis/brosisusal urogenital atrophy

smitted diseasee diaphragm

rapyr neurone lesional functionardiac failure (nocturia)ia

llitusipidusismlinking

Indevu

a Cartthe PatieInt 2010

b Card2005;95

c Nixoof urina2005;17

Table 3Disease-

UrogeQualitKingsIncont

a Shumof life mQuestion

b Wagof perso1996;47

c Ref. d Wym

tinence

these mclinica

5.4. Q

Qua

ill be discovered by examining the cranial nerves andoutow.

ation

veractive bladder (OAB) is a symptomatic diagnosis alluire a basic assessment in order to conrm the diag-ll as excluding any other underlying cause for lowert dysfunction.

ulture

eam specimen of urine should be sent for microscopy, sensitivity in all cases of incontinence.

ncy/volume chart

nts should complete a frequency/volume chart in order their uid intake and voiding pattern. As well as thevoids and incontinence episodes, the mean volumer a 24-h period can also be calculated as well as the

nocturnal volumes.

y severity scales

is now generally regarded as being the driving symp-B and is known to play an important role in thent of daytime frequency, nocturia and urgency incon-veral validated urgency scoring systems have beento attempt to measure urgency severity (Table 2) and

pleted by ththe quanticacy as welstrategies a

Generic eral measuof populatiotionnaires, designed to

6. Urodyn

Whilst ative of OABthose womet from uinclude urostudies.

6.1. Uroow

Althougchronic uriand frequenow rate an

6.2. Filling

Cystomeder at a corectum meency Severity Scale (IUSS)c

t R, Panayi D, Cardozo L, Khullar V. Reliability and normal ranges forerception of Intensity of Urgency Scale in asymptomatic women. BJU8326., Coyne KS, Versi E. Validation of the Urgency Perception Scale. BJU Int6.olman S, Sabounjian L, et al. A validated patient reported measureency severity in overactive bladder for use in clinical trials. J Urol7.

c quality of life questionnaires (Grade A).

istress inventory (UDI)a

e in persons with urinary incontinence (I-QoL)b

h Questionnaire (KHQ)c

e impact questionnaire (IIQ)d

SA, Wyman JF, Uebersax JS, McClish D, Fantl JA. Health related qualityes for women with urinary incontinence: the Incontinence Impact

and the urogenital distress inventory. Qual Life Res 1994;3:291306.H, Patrick DL, Bavendam TG, Martin ML, Buesching DP. Quality of lifeth urinary incontinence: development of a new measure. Urology2.

, Harkins SW, Taylor JR, Fantl JA. Psychosocial impact of urinary incon-en. Obstet Gynaecol 1987;70:37881.

e used in conjunction with frequency volume charts inctice.

of life

f life (QoL) is assessed by the use of questionnaires com-e patient alone or as part of the consultation and allowscation of morbidity and the evaluation of treatment ef-l as being a measure of how lives are affected and copingdopted.questionnaires, such as the Short Form 36 [7], are gen-res of QoL and are therefore applicable to a wide range

ns and clinical conditions whilst disease-specic ques-such as the Kings Health Questionnaire (KHQ) [8] are

focus on lower urinary tract symptoms (Table 3).

amic investigations

number of women complaining of symptoms sugges- may be managed on the basis of simple investigationsen with refractory or complex symptoms may ben-rodynamic investigations. Urodynamic investigationsowmetry, lling cystometry and pressure/ow voiding

metry

h voiding difculties are uncommon in women, a largenary residual may present with symptoms of urgencycy of micturition, so it is important to assess the urined to exclude a signicant urinary residual.

cystometry

try is used to describe retrograde lling of the blad-nstant rate. Pressure transducers in the bladder andasure pressure changes during lling and this allows

190 D. Robinson, L. Cardozo / Maturitas 71 (2012) 188 193

contra

the calculatactivity is dinvoluntaryspontaneoudynamic in

6.3. Pressur

Pressurefunction. A with outowated with dassociated wand outow[9].

7. Cystour

Althoughactivity it massociated addition cycomplaininrent inconti

8. Conserv

All womsures whichpatients druid intakeand alcohol

creasoms

addeFig. 1. Cystometrogram trace showing detrusor

ion of the subtracted detrusor pressure. Detrusor over-ened as a urodynamic observation characterised by

detrusor contractions during lling which may bes or provoked and can only be made following uro-vestigation (Fig. 1).

also insympt

8.1. Ble/ow studies

ow voiding studies are useful to determine voidinghigh voiding pressure with low ow may be associated

obstruction whilst a low pressure void may be associ-etrusor hypocontractility. Voiding dysfunction may beith the development of symptoms suggestive of OAB

obstruction is associated with detrusor overactivity

ethroscopy

endoscopy is not helpful in diagnosing detrusor over-ay be used to exclude other causes for the symptomswith OAB such as a bladder tumour or calculus. Instourethroscopy should be considered in all womeng of haematuria, painful bladder syndrome and recur-nence.

ative management

en with OAB benet from advice regarding simple mea- they can take to help alleviate their symptoms. Manyink too much and they should be told to reduce their

to between 1 and 1.5 l/day [10] and to avoid tea, coffee if these exacerbate their problem. In addition there is

Bladder [12] and boJarvis and Mretraining ioveractive bder drill groafter 6 mosymptom frlent early re

A meta-effective thinsufcientstimulationoor exercincontinencExcellence tinence (ICconsidered

9. Medical

Whilst aapy remainthere are a nability, commany of theof newer bctions during lling.

ing evidence to suggest that weight loss may improveof urinary incontinence [11].

r retrainingretraining was rst described by Jeffcoate and Francisth inpatient and outpatient therapy can be effective.illar [13] have reported a controlled trial of bladder

n 60 consecutive incontinent women with idiopathicladder. Following inpatient treatment, 90% of the blad-up were continent and 83.3% remained symptom freenths. In the control group 23.2% were continent andee due to the placebo effect. However, despite the excel-sults up to 40% of patients relapse within 3 years [14].analysis has concluded that bladder retraining is morean placebo and medical therapy although there is

evidence to support the effectiveness of electrical and too few studies to evaluate the effect of pelvicises and biofeedback in women with urinary urgee [15]. Nevertheless the National Institute of Clinical(NICE) [16] and International Consultation on Incon-I) [17] recommend that bladder retraining should be

as rst line treatment in all women with OAB.

management

conservative approach is justied initially drug ther-s integral in the management of women with OAB andumber of different agents available. Traditionally toler-pliance and persistence have limited the usefulness of

antimuscarinic agents although with the introductionladder selective drugs, once daily dosing and differing

D. Robinson, L. Cardozo / Maturitas 71 (2012) 188 193 191

Table 4Drugs used in the treatment of overactive bladder.

Antimuscarinic drugs Level of evidence Grade of recommendation

Darifenacin FesoterodineOxybutyninPropiverine Solifenacin Tolterodine Trospium

Ref. [18].

routes of admay increa

There ardrugs availarecently renence [18] A recomme

The mostudies, incoterodine, trospium), managemereturn to copooled RR a(p < 0.01). Asignicantlper day, redof urgency

Whilst tthe evidencavailable evand tolteropreparationinferior to extended re

Antimusvative therpatients symthose on an(RR 0.73; 9associated (RR 0.55; 9greater impapy with blalone (RR 0.signicant [

10. Oestro

The mosapy on the lgroup [27] ferent to thtrials were involved inoestrogen t

Systemithetic and incontinencconsideringeffect on inCI: 1.041.1local oestro

CI: 0.640.86) and overall there were 12 fewer voids in 24 h andless frequency and urgency.

The authors conclude that local oestrogen therapy for inconti-may be benecial although there was little evidence of longffectmene wo

coministre recent we ef

inve

frac

ilst tve thain oavesn wit

tem1] altre litssocit tharomoms.has b

simiitionthouigh reulatie apmateical

conectoorbisider

nclu

ractin to

oftepful ajorirsty. Foodu

y.

sear1 A1 A1 A1 A1 A1 A1 A

ministration it is possible that persistence with therapyse.e now a number of different licensed antimuscarinicble on the market within the UK. These have all beenviewed by the International Consultation on Inconti-(Table 4) and all have Level 1 evidence [19] and a Gradendation [20].st recent systematic review and meta-analysis of 83luding 30 699 patients and six different drugs (fes-oxybutynin, propiverine, solifenacin, tolterodine andsupports the efcacy of antimuscarinic therapy in thent of OAB. Overall there was a signicantly higherntinence favouring active treatment over placebo; thecross different studies and different drugs being 1.33.5ntimuscarinic therapy was also shown to be statisticallyy more effective in reduction of incontinence episodesuction in number of micturitions per day and reductionepisodes per day [21].hese data conrm the efcacy of antimuscarinic drugse comparing drugs with one another is less robust. Theidence would suggest that extended release oxybutynindine have superior efcacy to the immediate releases [22]. In addition solifenacin has been shown to be non-[23], and fesoterodine superior to [24,25] tolterodinelease.carinic therapy may be a useful addition to conser-apy. In a Cochrane review of 13 trials including 1770ptomatic improvement was more common amongsttimuscarinic therapy compared to bladder retraining5% CI 0.590.90) and combination treatment was alsowith more improvement than bladder training alone5% CI: 0.320.93). Similarly there was a trend towardsrovement with a combination of antimuscarinic ther-adder retraining compared to antimuscarinic therapy81; 95% CI: 0.611.06) although this was not statistically26].

gens and overactive bladder

t recent meta-analysis of the effect of oestrogen ther-ower urinary tract has been performed by the Cochraneand is notable as the conclusions are considerably dif-ose drawn from the previous review [28]. Overall 33identied, including 19 313 incontinent women (1262

nence term ereplacetinencdata toof adm

Motreatmimprovstudies

11. Re

Whservaticompl

Intrwomeis onlyties [3there ations asugges

Neusymptnerve offer aIn addtive alwith hromodinvasiv

Ultito medmay besor myhigh mbe con

12. Co

Oveis knowOAB isare helThe min the therapneuromsurger

13. Re trials of local administration) of which 9417 receivedherapy.c administration (of unopposed oral oestrogens syn-conjugated equine oestrogens) resulted in worsee than placebo (RR 1.32; 95% CI: 1.171.48). When

combination therapy there was a similar worseningcontinence when compared to placebo (RR 1.11; 95%8). There was some evidence suggesting that the use ofgen therapy may improve incontinence (RR 0.74; 95%

Antimusagents althpersistencealternative tance.

New drucalcium blo[39] showeclinical setts. The evidence would suggest that systemic hormonet using conjugated equine oestrogens may make incon-rse. In addition they comment that there are too fewment reliably on the dose, type of oestrogen and routeration.ent evidence would appear to suggest that combinationith antimuscarinic agents and vaginal oestrogens maycacy in women with OAB although at present the twostigating this have given conicting results [29,30].

tory OAB

he majority of patients with OAB will respond to con-erapy and drug treatment a minority will continue tof distressing lower urinary tract symptoms.ical Botulinum Toxin offers an alternative in thoseh intractable detrusor overactivity although the effectporary and there is a signicant risk of voiding difcul-hough these would appear to dose related [32]. Whilsttle long term data regarding the efcacy and complica-ated with repeat injections the current evidence wouldt repeat procedures are safe and remain effective [33].odulation may also be used in women with refractory

Peripheral neuromodulation using the posterior tibialeen shown to be effective [34] and would appear tolar improvement in QoL as antimuscarinic agents [35].

sacral neuromodulation has been shown to be effec-gh is expensive, more invasive and may be associatedvision rates [36]. More recently a cutaneous sacral neu-on system has been developed which may offer a lessproach [37].ly a small number of women who have failed to respondtherapy may benet from reconstructive surgery andsidered for a ileal diversion, clam cystoplasty or detru-my. However, reconstructive surgery is associated withdity and long term complications and really should onlyed when all other treatment modalities have failed.

sions

ve bladder is a common and distressing condition which have a signicant effect on QoL. The clinical diagnosis ofn one of exclusion although urodynamic investigationsin those women with refractory or unusual symptoms.ty of women will benet from conservative measures

instance although many will eventually require drugr those with refractory symptoms Botulinum Toxin andlation now offer effective alternatives to reconstructive

ch agenda

carinic drugs are currently the most commonly usedough may be associated with poor compliance and. The emergence of more bladder specic drugs androutes of delivery may help to improve patient accep-

gs are currently under development. Whilst the use ofcking agents [38] and potassium channel opening drugsd initial promise neither have proved to be useful in theing [40,41] and at present there are no further trials

192 D. Robinson, L. Cardozo / Maturitas 71 (2012) 188 193

being performed. More recently evidence from phase III studieswould suggest that 3 agonists may offer an alternative to antimus-carinic therapy [42] and Mirabegron has recently been launched inJapan. In addition there is now considerable evidence to suggestthat the senOAB and neUltimately of OAB synment modaand trouble

14. Practic

Overactivincreases

OAB is kn OAB is a a urodynachangeab

All womeinfection may be us

Conservatto starting

Women Botulinum

Reconstruhave not

Contributo

DR wrot

Competing

DR is a lectured forPzer and A

LC is a cfor Astellas

Provenanc

Commis

References

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[2] Stewart Wwomen: r

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e points

e bladder is a common condition and the prevalence with age.own to have a signicant impact on QoL.symptomatic diagnosis whilst detrusor overactivity ismic diagnosis. The terms, although often used inter-ly are not synonymous.n require basic assessment to exclude urinary tractand voiding dysfunction. Urodynamic investigationseful in women with persistent symptoms.ive measures should be used as rst line therapy prior

antimuscarinic therapy.with refractory OAB may benet from intravesical

Toxin or neuromodulation.ctive surgery should be reserved for those women whoresponded to all other treatment modalities.

rs

e the paper and LC proofread the paper.

interests

consultant for Astellas, Pzer, Ferring and Gynaecare; Astellas, Pzer and Gynaecare; researcher for Astellas,llergan.onsultant for Astellas, Pzer, Taevo and Lilly; lectured

and Pzer; researcher for Astellas, Pzer.

e and peer review

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Overactive bladder: Diagnosis and management1 Introduction2 Prevalence3 Pathophysiology4 Clinical presentation5 Investigation5.1 Urine culture5.2 Frequency/volume chart5.3 Urgency severity scales5.4 Quality of life

6 Urodynamic investigations6.1 Uroflowmetry6.2 Filling cystometry6.3 Pressure/flow studies

7 Cystourethroscopy8 Conservative management8.1 Bladder retraining

9 Medical management10 Oestrogens and overactive bladder11 Refractory OAB12 Conclusions13 Research agenda14 Practice pointsContributorsCompeting interestsProvenance and peer reviewReferences