Maturitas 71 (2012) 188193

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Maturitas
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Mini review
Overactive bladder: Diagnosis and management
Dudley Robinson

, Linda Cardozo
Department of Urogynaecology, Kings College Hospital, London, UK
a r t i c l e i n f o
Article history:
Received 3 November 2011
Received in revised form
15 November 2011
Accepted 17 November 2011
Keywords:
Overactive bladder
Urinary incontinence
Antimuscarinics
a b s t r a c t
Overactive bladder (OAB) is a clinical syndrome describing the symptom complex of urgency, with or
without urgency incontinence and is usually associated with frequency and nocturia. Whilst a number
of women may be managed based on a clinical diagnosis alone urodynamic studies may be useful in
those women with complex or refractory symptoms. In the rst instance all women will benet from a
conservative approach using bladder retraining although a number will require antimuscarinic therapy.
For those women with persistent symptoms following medical therapy alternative treatment modalities
such as intravesical Botulinum Toxin, neuromodulation or reconstructive surgery may be considered.
This review, whilst giving an overview of the syndrome, will focus on a practical clinical approach to
managing women with symptoms of overactive bladder (OAB).
2011 Published by Elsevier Ireland Ltd.
1. Introduction
Overactive bladder (OAB) is the term used to describe the
symptom complex of urinary urgency, usually accompanied by
frequency and nocturia, with or without urgency urinary incon-
tinence, in the absence of urinary tract infection or other obvious
pathology [1].
The aim of this review is to provide practical clinical advice
regarding the investigation and management of women complain-
ing of lower urinary tract symptoms suggestive of OAB as well as
providing an evidence based approach to treatment.
2. Prevalence
Epidemiological studies from North America have reported a
prevalence of OAB in women of 16.9% and the prevalence increases
with age rising to 30.9% in those over the age of 65 years [2]. Fur-
ther prevalence data from Europe [3] also has shown the overall
prevalence in men and women over the age of 40 years to be 16.6%.
Frequencywas themost commonlyreportedsymptom(85%) whilst
54% complained of urgency and 36% urgency incontinence.
More recently a further population based survey of lower uri-
nary tract symptoms in Canada, Germany, Italy, Sweden and the
United Kingdom has reported on 19165 men and women over
the age of 18 years [4]. Overall 11.8% were found to complain
of symptoms suggestive of OAB and 64.3% reported at least one

Corresponding author. Tel.: +0203 299 9000.

E-mail address: dudley.robinson@nhs.net (D. Robinson).
urinary symptom. Nocturia was the most prevalent lower uri-
nary tract symptom being reported by 48.6% of men and 54.5% of
women.
3. Pathophysiology
The symptoms of OAB are due to involuntary contractions of the
detrusor muscle during the lling phase of the micturition cycle.
Theseinvoluntarycontractions aretermeddetrusor overactivity[1]
and are mediated by acetylcholine-induced stimulation of bladder
muscarinic receptors [5]. However OAB is not synonymous with
detrusor overactivity as the former is a symptom based diagnosis
whilst the latter is a urodynamic diagnosis. It has been estimated
that 64% of patients with OAB have urodynamically proven detru-
sor overactivity and that 83% of patients with detrusor overactivity
have symptoms suggestive of OAB [6]. Hence the terms are not
synonymous.
4. Clinical presentation
Overactive bladder usually presents witha multiplicity of symp-
toms. Those most commonly seen are urgency, daytime frequency,
nocturia, urgency incontinence, stress incontinence, nocturnal
enuresis and often coital incontinence. However it is important to
remember that there are numerous other causes of urgency and
frequency (Table 1).
There are no specic clinical signs in women with overactive
bladder 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
0378-5122/$ see front matter 2011 Published by Elsevier Ireland Ltd.
doi:10.1016/j.maturitas.2011.11.016
D. Robinson, L. Cardozo / Maturitas 71 (2012) 188193 189
Table 1
Common causes of frequency and urgency of micturition.
Urological
Urinary tract infection
Detrusor overactivity
Small-capacity bladder
Interstitial cystitis
Chronic urinary retention/chronic urinary residual
Bladder mucosal lesion, e.g. papilloma
Bladder calculus
Urethral syndrome
Urethral diverticulum
Urethral obstruction
Gynaecological
Pregnancy
Stress incontinence
Cystocoele
Pelvic mass, e.g. broids
Previous pelvic surgery
Radiation cystitis/brosis
Postmenopausal urogenital atrophy
Sexual
Coitus
Sexually transmitted disease
Contraceptive diaphragm
Medical
Diuretic therapy
Upper motor neurone lesion
Impaired renal function
Congestive cardiac failure (nocturia)
Hypokalaemia
Endocrine
Diabetes mellitus
Diabetes insipidus
Hypothyroidism
Psychological
Excessive drinking
Habit
Anxiety
sclerosis will be discovered by examining the cranial nerves and
S2, 3 and 4 outow.
5. Investigation
Whilst overactive bladder (OAB) is a symptomatic diagnosis all
patients require a basic assessment in order to conrm the diag-
nosis as well as excluding any other underlying cause for lower
urinary tract dysfunction.
5.1. Urine culture
A midstreamspecimen of urine should be sent for microscopy,
culture and sensitivity in all cases of incontinence.
5.2. Frequency/volume chart
All patients should complete a frequency/volume chart in order
to evaluate their uid intake and voiding pattern. As well as the
number of voids and incontinence episodes, the mean volume
voided over a 24-h period can also be calculated as well as the
diurnal and nocturnal volumes.
5.3. Urgency severity scales
Urgency is now generally regarded as being the driving symp-
tom of OAB and is known to play an important role in the
development of daytime frequency, nocturia and urgency incon-
tinence. Several validated urgency scoring systems have been
developed to attempt to measure urgency severity (Table 2) and
Table 2
Urgency severity scales.
Patient Perception of Intensity of Urgency Score (PPIUS)
a
Urgency Perception Score (UPS)
b
Indevus Urgency Severity Scale (IUSS)
c
a
Cartwright R, Panayi D, Cardozo L, Khullar V. Reliability and normal ranges for
the Patients Perception of Intensity of Urgency Scale in asymptomatic women. BJU
Int 2010;105:8326.
b
Cardozo L, Coyne KS, Versi E. Validation of the Urgency Perception Scale. BJU Int
2005;95:5916.
c
Nixon A, Colman S, Sabounjian L, et al. A validated patient reported measure
of urinary urgency severity in overactive bladder for use in clinical trials. J Urol
2005;174:6047.
Table 3
Disease-specic quality of life questionnaires (Grade A).
Urogenital distress inventory (UDI)
a
Quality of life in persons with urinary incontinence (I-QoL)
b
Kings Health Questionnaire (KHQ)
c
Incontinence impact questionnaire (IIQ)
d
a
Shumaker SA, Wyman JF, Uebersax JS, McClish D, Fantl JA. Health related quality
of life measures for women with urinary incontinence: the Incontinence Impact
Questionnaire and the urogenital distress inventory. Qual Life Res 1994;3:291306.
b
Wagner TH, Patrick DL, BavendamTG, Martin ML, Buesching DP. Quality of life
of persons with urinary incontinence: development of a new measure. Urology
1996;47:6772.
c
Ref. [8].
d
Wyman JF, Harkins SW, Taylor JR, Fantl JA. Psychosocial impact of urinary incon-
tinence in women. Obstet Gynaecol 1987;70:37881.
these may be used in conjunction with frequency volume charts in
clinical practice.
5.4. Quality of life
Qualityof life(QoL) is assessedbytheuseof questionnaires com-
pleted by the patient alone or as part of the consultation and allows
thequanticationof morbidityandtheevaluationof treatment ef-
cacy as well as being a measure of howlives are affected and coping
strategies adopted.
Generic questionnaires, such as the Short Form36 [7], are gen-
eral measures of QoL and are therefore applicable to a wide range
of populations and clinical conditions whilst disease-specic ques-
tionnaires, such as the Kings Health Questionnaire (KHQ) [8] are
designed to focus on lower urinary tract symptoms (Table 3).
6. Urodynamic investigations
Whilst a number of women complaining of symptoms sugges-
tive of OAB may be managed on the basis of simple investigations
those women with refractory or complex symptoms may ben-
et from urodynamic investigations. Urodynamic investigations
includeuroowmetry, llingcystometryandpressure/owvoiding
studies.
6.1. Uroowmetry
Although voiding difculties are uncommon in women, a large
chronic urinary residual may present with symptoms of urgency
and frequency of micturition, so it is important to assess the urine
owrate and to exclude a signicant urinary residual.
6.2. Filling cystometry
Cystometry is used to describe retrograde lling of the blad-
der at a constant rate. Pressure transducers in the bladder and
rectum measure pressure changes during lling and this allows
190 D. Robinson, L. Cardozo / Maturitas 71 (2012) 188193
Fig. 1. Cystometrogramtrace showing detrusor contractions during lling.
the calculation of the subtracted detrusor pressure. Detrusor over-
activity is dened as a urodynamic observation characterised by
involuntary detrusor contractions during lling which may be
spontaneous or provoked and can only be made following uro-
dynamic investigation (Fig. 1).
6.3. Pressure/ow studies
Pressure ow voiding studies are useful to determine voiding
function. A high voiding pressure with lowowmay be associated
with outowobstruction whilst a lowpressure void may be associ-
ated with detrusor hypocontractility. Voiding dysfunction may be
associated with the development of symptoms suggestive of OAB
and outow obstruction is associated with detrusor overactivity
[9].
7. Cystourethroscopy
Although endoscopy is not helpful in diagnosing detrusor over-
activity it may be used to exclude other causes for the symptoms
associated with OAB such as a bladder tumour or calculus. In
addition cystourethroscopy should be considered in all women
complaining of haematuria, painful bladder syndrome and recur-
rent incontinence.
8. Conservative management
All women with OAB benet fromadvice regarding simple mea-
sures which they can take to help alleviate their symptoms. Many
patients drink too much and they should be told to reduce their
uid intake to between 1 and 1.5l/day [10] and to avoid tea, coffee
and alcohol if these exacerbate their problem. In addition there is
also increasing evidence to suggest that weight loss may improve
symptoms of urinary incontinence [11].
8.1. Bladder retraining
Bladder retraining was rst described by Jeffcoate and Francis
[12] and both inpatient and outpatient therapy can be effective.
Jarvis and Millar [13] have reported a controlled trial of bladder
retraining in 60 consecutive incontinent women with idiopathic
overactive bladder. Following inpatient treatment, 90% of the blad-
der drill group were continent and 83.3% remained symptom free
after 6 months. In the control group 23.2% were continent and
symptomfreeduetotheplaceboeffect. However, despitetheexcel-
lent early results up to 40% of patients relapse within 3 years [14].
A meta-analysis has concluded that bladder retraining is more
effective than placebo and medical therapy although there is
insufcient evidence to support the effectiveness of electrical
stimulation and too few studies to evaluate the effect of pelvic
oor exercises and biofeedback in women with urinary urge
incontinence [15]. Nevertheless the National Institute of Clinical
Excellence (NICE) [16] and International Consultation on Incon-
tinence (ICI) [17] recommend that bladder retraining should be
considered as rst line treatment in all women with OAB.
9. Medical management
Whilst a conservative approach is justied initially drug ther-
apy remains integral in the management of women with OAB and
there are a number of different agents available. Traditionally toler-
ability, compliance and persistence have limited the usefulness of
many of the antimuscarinic agents although with the introduction
of newer bladder selective drugs, once daily dosing and differing
D. Robinson, L. Cardozo / Maturitas 71 (2012) 188193 191
Table 4
Drugs used in the treatment of overactive bladder.
Antimuscarinic drugs Level of evidence Grade of recommendation
Darifenacin 1 A
Fesoterodine 1 A
Oxybutynin 1 A
Propiverine 1 A
Solifenacin 1 A
Tolterodine 1 A
Trospium 1 A
Ref. [18].
routes of administration it is possible that persistence with therapy
may increase.
There are now a number of different licensed antimuscarinic
drugs available on the market within the UK. These have all been
recently reviewed by the International Consultation on Inconti-
nence [18] (Table 4) and all have Level 1 evidence [19] and a Grade
A recommendation [20].
The most recent systematic review and meta-analysis of 83
studies, including 30699 patients and six different drugs (fes-
oterodine, oxybutynin, propiverine, solifenacin, tolterodine and
trospium), supports the efcacy of antimuscarinic therapy in the
management of OAB. Overall there was a signicantly higher
return to continence favouring active treatment over placebo; the
pooledRRacross different studies anddifferent drugs being 1.33.5
(p<0.01). Antimuscarinic therapy was alsoshowntobe statistically
signicantly more effective in reduction of incontinence episodes
per day, reduction in number of micturitions per day and reduction
of urgency episodes per day [21].
Whilst these data conrm the efcacy of antimuscarinic drugs
the evidence comparing drugs with one another is less robust. The
availableevidencewouldsuggest that extendedreleaseoxybutynin
and tolterodine have superior efcacy to the immediate release
preparations [22]. Inadditionsolifenacinhas beenshowntobenon-
inferior to [23], and fesoterodine superior to [24,25] tolterodine
extended release.
Antimuscarinic therapy may be a useful addition to conser-
vative therapy. In a Cochrane review of 13 trials including 1770
patients symptomatic improvement was more common amongst
those on antimuscarinic therapy compared to bladder retraining
(RR 0.73; 95% CI 0.590.90) and combination treatment was also
associated with more improvement than bladder training alone
(RR 0.55; 95% CI: 0.320.93). Similarly there was a trend towards
greater improvement with a combination of antimuscarinic ther-
apy with bladder retraining compared to antimuscarinic therapy
alone(RR0.81; 95%CI: 0.611.06) althoughthis was not statistically
signicant [26].
10. Oestrogens and overactive bladder
The most recent meta-analysis of the effect of oestrogen ther-
apy on the lower urinary tract has been performed by the Cochrane
group [27] and is notable as the conclusions are considerably dif-
ferent to those drawn from the previous review [28]. Overall 33
trials were identied, including 19313 incontinent women (1262
involved in trials of local administration) of which 9417 received
oestrogen therapy.
Systemic administration (of unopposed oral oestrogens syn-
thetic and conjugated equine oestrogens) resulted in worse
incontinence than placebo (RR 1.32; 95% CI: 1.171.48). When
considering combination therapy there was a similar worsening
effect on incontinence when compared to placebo (RR 1.11; 95%
CI: 1.041.18). There was some evidence suggesting that the use of
local oestrogen therapy may improve incontinence (RR 0.74; 95%
CI: 0.640.86) and overall there were 12 fewer voids in 24h and
less frequency and urgency.
The authors conclude that local oestrogen therapy for inconti-
nence may be benecial although there was little evidence of long
term effects. The evidence would suggest that systemic hormone
replacement using conjugated equine oestrogens may make incon-
tinence worse. In addition they comment that there are too few
data to comment reliably on the dose, type of oestrogen and route
of administration.
Morerecent evidencewouldappear tosuggest that combination
treatment with antimuscarinic agents and vaginal oestrogens may
improve efcacy in women with OAB although at present the two
studies investigating this have given conicting results [29,30].
11. Refractory OAB
Whilst the majority of patients with OAB will respond to con-
servative therapy and drug treatment a minority will continue to
complain of distressing lower urinary tract symptoms.
Intravesical Botulinum Toxin offers an alternative in those
women with intractable detrusor overactivity although the effect
is only temporary and there is a signicant risk of voiding difcul-
ties [31] although these would appear to dose related [32]. Whilst
there are little long termdata regarding the efcacy and complica-
tions associated with repeat injections the current evidence would
suggest that repeat procedures are safe and remain effective [33].
Neuromodulation may also be used in women with refractory
symptoms. Peripheral neuromodulation using the posterior tibial
nerve has been shown to be effective [34] and would appear to
offer a similar improvement in QoL as antimuscarinic agents [35].
In addition sacral neuromodulation has been shown to be effec-
tive although is expensive, more invasive and may be associated
with high revision rates [36]. More recently a cutaneous sacral neu-
romodulation system has been developed which may offer a less
invasive approach [37].
Ultimatelyasmall number of women whohavefailedtorespond
to medical therapy may benet from reconstructive surgery and
may be considered for a ileal diversion, clamcystoplasty or detru-
sor myectomy. However, reconstructive surgery is associated with
high morbidity and long termcomplications and really should only
be considered when all other treatment modalities have failed.
12. Conclusions
Overactivebladder is acommonanddistressingconditionwhich
is knowntohave a signicant effect onQoL. The clinical diagnosis of
OAB is often one of exclusion although urodynamic investigations
are helpful in those women with refractory or unusual symptoms.
The majority of women will benet from conservative measures
in the rst instance although many will eventually require drug
therapy. For those with refractory symptoms BotulinumToxin and
neuromodulation nowoffer effective alternatives to reconstructive
surgery.
13. Research agenda
Antimuscarinic drugs are currently the most commonly used
agents although may be associated with poor compliance and
persistence. The emergence of more bladder specic drugs and
alternative routes of delivery may help to improve patient accep-
tance.
New drugs are currently under development. Whilst the use of
calciumblocking agents [38] and potassiumchannel opening drugs
[39] showed initial promise neither have proved to be useful in the
clinical setting [40,41] and at present there are no further trials
192 D. Robinson, L. Cardozo / Maturitas 71 (2012) 188193
being performed. More recently evidence from phase III studies
wouldsuggest that
3
agonists may offer analternative toantimus-
carinic therapy [42] and Mirabegron has recently been launched in
Japan. In addition there is now considerable evidence to suggest
that the sensory pathways also play a role in the development of
OAB and neurokinin antagonists remain under investigation [43].
Ultimately perhaps a better understanding of the pathophysiology
of OAB syndrome may facilitate the development of new treat-
ment modalities allowing effective treatment of such a common
and troublesome condition.
14. Practice points

Overactive bladder is a common condition and the prevalence

increases with age.

OAB is known to have a signicant impact on QoL.

OAB is a symptomatic diagnosis whilst detrusor overactivity is

a urodynamic diagnosis. The terms, although often used inter-
changeably are not synonymous.

All women require basic assessment to exclude urinary tract

infection and voiding dysfunction. Urodynamic investigations
may be useful in women with persistent symptoms.

Conservative measures should be used as rst line therapy prior

to starting antimuscarinic therapy.

Women with refractory OAB may benet from intravesical

BotulinumToxin or neuromodulation.

Reconstructive surgery should be reserved for those women who

have not responded to all other treatment modalities.
Contributors
DR wrote the paper and LC proofread the paper.
Competing interests
DR is a consultant for Astellas, Pzer, Ferring and Gynaecare;
lectured for Astellas, Pzer and Gynaecare; researcher for Astellas,
Pzer and Allergan.
LC is a consultant for Astellas, Pzer, Taevo and Lilly; lectured
for Astellas and Pzer; researcher for Astellas, Pzer.
Provenance and peer review
Commissioned and externally peer reviewed.
References
[1] Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynaecological
Association (IUGA)/International Continence Society (ICS) joint report on the
terminologyfor femalepelvic oor dysfunction. Int Urogynecol J 2010;21:526.
[2] Stewart WF, Corey R, Herzog AR, et al. Prevalence of overactive bladder in
women: results fromthe NOBLE program. Int Urogynecol J 2001;12(3):S66.
[3] MilsomI, Abrams P, Cardozo L, Roberts RG, Thuroff J, Wein AJ. Howwidespread
are the symptoms of overactive bladder and how are they managed? A
population-based prevalence study. BJU Int 2001;87(9):7606.
[4] IrwinDE, MilsomI, Hunskaar S, et al. Population-basedsurvey of urinary incon-
tinence, overactive bladder and other lower urinary tract symptoms in ve
countries; results of the EPIC study. Eur Urol 2006;50:130615.
[5] Anderson KE. The overactive bladder: pharmacologic basis of drug treatment.
Urology 1997;50:7489.
[6] Hashim H, Abrams P. Is the bladder a reliable witness for predicting detrusor
overactivity? J Urol 2006;175:1915.
[7] Jenkinson C, Coulter A, Wright L. Short Form36 (SF-36) health survey question-
naire. Normative data for adults of working age. Br Med J 1993;306:143740.
[8] Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A new questionnaire to
assess the quality of life of urinary incontinent women. Br J Obstet Gynaecol
1997;104:13749.
[9] Van Koeveringe GA. Effect of partial urethral obstruction on force development
of the guinea pig bladder. Neurourol Urodyn 1993;12:5556.
[10] Swithinbank L, HashimH, Abrams P. The effect of uid intake on urinary symp-
toms in women. J Urol 2005;174(July (1)):1879.
[11] Subak LL, Wing R, West DS, et al. PRIDE InvestigatorsWeight loss to treat
urinary incontinence in overweight and obese women. N Engl J Med
2009;360(5):48190.
[12] Jeffcoate TNA, Francis WJA. Urgency incontinence in the female. Am J Obstet
Gynecol 1966;94:60418.
[13] Jarvis GT, Millar DR. Controlled trial of bladder drill for overactive bladder. Br
Med J 1980;281:13223.
[14] Holmes DM, Stone AR, Barry PR, Richards CJ, Stephenson TP. Bladder training
years on. Br J Urol 1983;55:6604.
[15] Berghmans LC, Hendricks HJ, de Bie RA, van Waalwijk van Doorn ES, Bo
K, van Kerrebroeck PE. Conservative treatment of urge urinary incontinence
in women: a systematic review of randomised clinical trials. Br J Urol Int
2000;85:25463.
[16] NICE Guideline 40. The Management of Urinary Incontinence in Women.
Department of Health. www.nice.org.uk; 2006.
[17] Hay-Smith J, Berghmans B, Burgio K, et al. Adult conservative management. In:
Abrams P, Cardozo L, Khoury S, Wein A, editors. Incontinence. 4th edition Paris,
France: Health Publication Ltd.; 2009. p. 1025120 [Editions 21].
[18] Andersson KE, Chapple CR, Cardozo L, et al. Pharmacological treatment of
urinary incontinence. In: Abrams P, CardozoL, Khoury S, WeinA, editors. Incon-
tinence. 4th edition Paris, France: Health Publication Ltd.; 2009. p. 631700
[Editions 21].
[19] Hadorn DC, Baker D, Hodges JS, Hicks N. Rating the quality of evidence for
clinical practice guidelines. J Clin Epidemiol 1996;49(7):74954.
[20] Harbour R, Miller J. A new system for grading recommendations in evidence
based guidelines. BMJ 2001;323:3346.
[21] Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D. The effects
of antimuscarinic treatments in overactive bladder: an update of a systematic
reviewand meta-analysis. Eur Urol 2008;54(3):54362.
[22] Diokno AC, Appell RA, Sand PK, et al. OPERA Stuy Group. Prospective,
randomised, double blind study of the efcacy and tolerability of the extended-
release formulations of oxybutynin and tolterodine for overactive bladder:
results of the OPERA trial. Mayo Clin Proc 2003;78(6):68795.
[23] Chapple CR, Martinez-Garcia R, Selvaggi L, et al. A comparison of the ef-
cacy and tolerability of solifenacin succinate and extended release tolterodine
at treating overactive bladder syndrome: results of the STAR trial. Eur Urol
2005;48:46470.
[24] Herschorn S, Swift S, Guan Z, et al. Comparison of fesoterodine and toltero-
dine extended release for the treatment of overactive bladder: a head to head
placebo controlled trial. BJU Int 2009;105:5866.
[25] KaplanSA, Schneider T, Foote JE, GuanZ, CarlssonM, Gong J. Superior efcacy of
fesoterodine over tolterodine extendedrelease withrapidonset: a prospective,
head-to-head, placebo-controlled trial. BJU Int 2011;107(9):143240.
[26] Alhasso AA, McKinlay J, Patrick K, Stewart L. Anticholinergic drugs versus non
drug active therapies for overactive bladder syndrome in adults. Cochrane
Database Syst Rev 2006;(4), doi:10.1002/14651858.CD003193.pub3. Art No:
CD003193.
[27] Cody JD, Richardson K, Moehrer B, Hextall A, Glazener CMA. Oestrogen therapy
for urinary incontinence in post-menopausal women. Cochrane Database Syst
Rev 2009;(4), doi:10.1002/14651858.CD001405.pub2. Art. No: CD001405.
[28] Moehrer B, Hextall A, Jackson S. Oestrogens for urinary incontinence. Cochrane
Database Syst Rev 2003;(2).
[29] Tseng LH, Wang AC, Chang YL, Soong YK, Lloyd LK, Ko YJ. Randomized compar-
ison of tolterodine with vaginal estrogen cream versus tolterodine alone for
the treatment of postmenopausal women with overactive bladder syndrome.
Neurourol Urodyn 2009;28(1):4751.
[30] Serati M, Salvatore S, Uccella S, Cardozo L, Bolis P. Is there a synergistic effect of
topical oestrogens whenadministeredwithantimuscarinics inthetreatment of
symptomatic detrusor overactivity? Eur Urol 2009;55(March (3)):7139 [Epub
2008 June 20].
[31] Popat R, Apostolidis A, Kalsi V, Gonzales G, Fowler CJ, Dasgupta P. A compar-
ison between the response of patients with idiopathic detrusor overactivity
and neurogenic detrusor overactivity to the rst intradetrusor injection of
Botulinum-A toxin. J Urol 2005;174:9849.
[32] Dmochowski R, Chapple C, Nitti V, et al. Efcacy and safety of onabotulinum
toxin A for idiopathic overactive bladder: a double-blind, placebo controlled
randomised dose ranging trial. J Urol 2010;184:241622.
[33] Sahai A, Dowson C, Kahn MS, Dasgupta P. Repeated injections of botulinum
toxin-A for idiopathic detrusor overactivity. Urology 2010;75:5528.
[34] Vandoninick V, van Balken MR, Finazzi Agro E, et al. Posterior tibial nerve stim-
ulation in the treatment of urge incontinence. Neurourol Urodyn 2003;22:17
23.
[35] Peters KM, Macdiarmid SA, Wooldridge LS, et al. Randomised trial of percu-
taneous tibial nerve stimulation versus extended release tolterodine: results
fromthe overactive bladder innovative therapy trial. J Urol 2009;182:105561.
[36] van Kerrebroeck PE, van Voskuilen AC, Heesakkers JP, et al. Results of
sacral neuromodulation therapy for urinary voiding dysfunction: outcomes
of a prospective, worldwide clinical study. J Urol 2007;178(November
(5)):202934.
[37] Monga A, Dmochowski R, Miller D. Evaluation of a novel, non invasive, patient-
managed neuromodulation system (PMNS) on urgency urinary incontinence
and patient reported outcomes in subjects with overactive bladder syndrome
who had previously failed therapy: a four week, multicentre, prospective ran-
domised trial. Neurourol Urodyn 2011;30:9368.
[38] Levin RM, Kitada S, Hayes L, et al. Experimental hyperreexia: effect of intrav-
esical administration of various agents. Pharmacology 1991;42:54.
D. Robinson, L. Cardozo / Maturitas 71 (2012) 188193 193
[39] Andersson KE. The overactive bladder: pharmacologic basis of drug treatment.
Urology 1997;50:74.
[40] Laval KU, Lutzeyer W. Spontaneous phasic activity of the detrusor: a cause of
uninhibited contractions in unstable bladder. Urol Int 1980;35:1827.
[41] Chapple C, Patroneva A, Raines S. Effect of an ATP-sensitive potassiumchannel
opener insubjects withoveractivebladder: arandomizeddouble-blindplacebo
controlled study (ZD0947IL/0004). Eur Urol 2006:87986.
[42] Chapple CR, Yamaguchi O, Ridder A. Clinical proof of concept study (Blossom)
shows novel 3 adrenoceptor agonist YM178 is effective and well tolerated
in the treatment of symptoms of overactive bladder. Eur Urol Suppl 2008;7:
239.
[43] Green SA, Alon A, Ianus J, Mc Naughton, Tozzi CA, Reiss TF. Efcacy and safety of
a neurokinin-1 receptor antagonist inpostmenopausal womenwithoveractive
bladder with urge urinary incontinence. J Urol 2006;176:253540.