Review - Neuro-urology – Voiding Dysfunction
A Shifted Paradigm for the Further Understanding,
Evaluation, and Treatment of Lower Urinary
Tract Symptoms in Men: Focus on the Bladder
Christopher R. Chapplea,*, Claus G. Roehrbornb
aThe Royal Hallamshire Hospital, Sheffield, UK
bThe University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
Lower urinary tract symptoms (LUTS) are associated
with great emotional costs  to individuals and
substantial economic costs to society . The pre-
valence and severity of LUTS increase with age ,
and the progressive growth of the aged population
group has broadened the societal impact of LUTS.
european urology 49 (2006) 651–659
available at www.sciencedirect.com
journal homepage: www.europeanurology.com
Accepted February 3, 2006
Published online ahead of
print on February 17, 2006
Benign prostatic hyperplasia
Lower urinary tract
Lower urinary tract symptoms (LUTS) are highly prevalent among older
men and have a negative impact on health-related quality of life. Fre-
quent comorbidity with potential prostatic disease adds complexity to
the management of male LUTS. In this review, we discuss the patho-
physiological conditions that underlie male LUTS, and examine the
relationship between symptoms and urodynamic findings. The contri-
bution of bladder dysfunction to male LUTS, with a particular emphasis
on overactive bladder (OAB) symptoms, is explored. We also consider
pharmacotherapeutic options for male LUTS. Pharmacotherapies that
target the prostate (a1-receptor antagonists and 5a-reductase inhibitors)
often fail to alleviate OAB symptoms, and may not be the most appro-
priate therapy for men with storage LUTS. Multiple studies have sug-
gested that antimuscarinic therapy alone or in combination with a1-
receptor antagonists improve OAB symptoms in men with and without
bladder outlet obstruction. Although these agents may represent appro-
priate first-line therapies for men with OAB symptoms, the therapeutic
potential of antimuscarinics alone or in combination with a1-receptor
antagonists in this population should be evaluated in large-scale, well-
designed clinical trials.
# 2006 Published by Elsevier B.V.
* Corresponding author. The Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2 JF,
United Kingdom. Tel. +44 74 271 2559; Fax: +44 74 279 7841.
E-mail address: email@example.com (C.R. Chapple).
0302-2838/$ – see front matter # 2006 Published by Elsevier B.V.doi:10.1016/j.eururo.2006.02.018
LUTS comprise storage symptoms (daytime urinary
voiding symptoms (slow stream, splitting or spray-
ing, intermittency, hesitancy, straining, terminal
dribble), and postmicturition symptoms (sensation
A large-scale multinational study revealed that 90%
of men aged 50 to 80 suffer from potentially trouble-
some LUTS . Questionnaire data from 1,271 men
voiding symptoms . The same study demonstra-
ted that voiding symptoms were the most common
male LUTS, but that storage symptoms made up four
of the five most bothersome LUTS. Although LUTS
are also highly prevalent in women, their frequent
plexity to the management of male LUTS.
This review focuses on a number of contempor-
ary issues that relate to the management of male
LUTS. First, we discuss the appropriate terminology
for categorizing the pathophysiological conditions
underlying male LUTS. Second, we review the
relationship between symptoms and urodynamic
findings. The relative contribution of bladder dys-
function to male LUTS, with a particular emphasis
on the subset of storage symptoms that characterize
overactive bladder (OAB) syndrome, is explored.
Finally, we consider pharmacotherapeutic options
symptoms. We emphasize the need for large,
placebo-controlled trials to investigate the efficacy
and safety of antimuscarinics for the treatment of
OAB in men, when used alone or in combination
with a1-receptor antagonists.
2. LUTS terminology
Historically, a number of terms such as prostatism,
symptomsofbenign prostatichyperplasia(BPH), and
clinical BPH have been used to describe male LUTS.
However, we recommend that thesepseudodiagnos-
tic terms be eliminated from the medical vocabulary
because not all male storage and voiding symptoms
are prostate related [6,7]. In fact, relationships bet-
prostatic conditions are weak . Thus, Abrams 
and Holtgrewe  recommended the use of the term
LUTS. The term BPH should be reserved for histo-
prostate . Berry et al.  combined the results of
five major studies and reported that the prevalence
of histologically confirmed BPH at autopsy increased
from 42% in men aged 50 to 59 to 88% in men older
than 80. BPH is often associated with LUTS, but LUTS
generally cannot be used to make a definitive
diagnosis of BPH . Extraprostatic conditions
associated with LUTS include bladder dysfunction,
psychogenic disorders, congestive heart failure, and
polypharmacy . Only 25%–50% of men with
histologically confirmed BPH have LUTS .
Benign prostatic enlargement (BPE) is caused by
BPH. The term prostatic enlargement should be used
when BPH has not been histologically confirmed .
Only about half of men with BPH will develop BPE
which is characterized by increased detrusor pres-
sure and reduced urine flow rate. BOO is diagnosed
using simultaneous measurements of flow rate and
detrusor pressure obtained during urodynamic
pressure-flow studies that use criteria defined by
the International Continence
caused by BPE has both static (increased tissue
mass) and dynamic (increased smooth muscle tone)
components in the prostate , which represent
independent targets for pharmacotherapy.
LUTS, when suggestive of BOO, is ‘‘a term used
when a man complains predominantly of voiding
symptoms in the absence of infection or obvious
pathology other than possible causes of outlet
obstruction’’ . This term should be used until
pressure-flow studies have confirmed the presence
of BOO, because many men with LUTS do not have
BOO. In a study based in the United Kingdom and
Italy, Laniado et al.  reported urodynamically
confirmed BOO in only 48% of referred men with
pressure-flow studies revealed that 301 (53%) had
BOO . However, LUTS that are suggestive of BOO
may be caused by a poorly functioning detrusor
instead of prostatic pathology .
In summary, LUTS may result from a complex
interplay of pathophysiological influences, includ-
ing prostatic pathology and bladder dysfunction.
LUTS include all storage and voiding symptoms, and
the term LUTS should be used in place of terms like
BPH or BOO unless the latter conditions have been
confirmed by histology or urodynamics, respec-
tively. OAB symptoms form a subset of storage LUTS
(urgency, frequency, urgency urinary incontinence
[UUI], and nocturia). The use of incorrect and
inconsistent terminology may lead to confusion
among clinicians and patients and mismanagement
of the conditions that underlie male LUTS.
Society . BOO
OAB is characterized by urinary urgency, with or
without UUI, usually with frequency and nocturia
european urology 49 (2006) 651–659
. Thus, OAB comprises the same symptoms as
storage LUTS, and excludes types of incontinence
other than UUI. OAB affects approximately 16% of
men and women in the United States  and
Europe . It is similar to LUTS, and its prevalence
that the prevalence of OAB increased from 3% in
men aged 40 to 44 to 42% in those older than 75.
Unlike most women with OAB, most men with OAB
do not experience incontinence (55% versus 16%,
OAB is bothersome and has negative effects on
health-related quality of life [16,18]. Ninety-two
percent of men with at least 9 micturitions/day
reported that frequency was at least ‘‘a bit of a
problem’’ . Peters et al.  reported that at least
80% of men with urinary urgency and/or UUI and
64% of those with nocturia reported some degree of
bother associated with these symptoms.
Male OAB symptoms are often caused by bladder
dysfunctions such as detrusor overactivity (DO) and
impaired detrusor contractility, BOO, or a combina-
tion of bladder dysfunction and BOO . DO is a
frequent cause of OAB symptoms and is urodyna-
mically characterized by involuntary detrusor con-
tractions during the bladder filling phase . DO and
BOO often occur together. In one study, 45% of 162
men with LUTS had both BOO and DO . Two
independent studies reported that nearly 50% of
men with LUTS and urodynamically confirmed BOO
had DO [22,23]. Similarly, Hyman et al.  con-
firmed DO in 50 (46%) of 109 men with OAB
symptoms and BOO.
BOO may cause DO via cholinergic denervation of
the detrusor and consequent supersensitivity of
bladder outlet resistance may also result in ische-
mia, increased detrusor collagen content, changes
in electrical properties of detrusor smooth muscle
cells , and reorganization of the spinal micturi-
tion reflex , all of which are associated with
the development of DO in animal models. However,
comorbid BOO and DO are not always evidence of a
cause-and-effect relationship between these two
OAB symptoms can be caused solely by bladder
dysfunction that is independent of prostatic pathol-
ogy. The observation that many men with OAB
symptoms do not have BOO  underscores the
potential role of bladder dysfunction. The fact that
OAB symptoms are not limited to men provides
further support for this assertion, bearing in mind
that female BOO is extremely uncommon.
OAB is reasonably well correlated with DO;
however, voiding symptoms correlate poorly with
BOO. Therefore, scores on the storage and voiding
subscales of the American Urological Association
(AUA) symptom index did not differ significantly
between men and women aged 55–79 who attended
a health fair in Milwaukee . A study of more than
4,000 Japanese men and women at least 40 revealed
for voiding symptoms in men, but comparable
storage symptom scores between men and women
. Romanzi et al.  evaluated men and women
with persistent storage symptoms and reported that
89% of patients whose primary symptoms were
frequency and urgency had urodynamically con-
firmed DO. In patients with Parkinson’s disease and
LUTS, storage symptoms that were determined by
the IPSS demonstrated significant negative correla-
tions with volume at first desire to void and
maximum bladder capacity and significant positive
correlations with uninhibited bladder contractions
during the storage phase . Furthermore, Barry
et al.  reported that symptoms of frequency,
urgency, and nocturia were not significantly corre-
lated with mean flow rate, peak flow rate (Qmax),
postvoid residual volume (PVR), prostate size, or
levels of prostate-specific antigen among 198 parti-
cipants in the BPH Treatment Outcomes Pilot Study.
Finally, urgency, UUI, frequency, and nocturia were
not significantly correlated with Qmax, urethral
resistance, or prostate size in 107 men with LUTS
that are suggestive of BPH. However, all four OAB
symptoms were significantly correlated with cysto-
metrically diagnosed DO .
Symptom scores and urodynamic studies should
be considered separately in the evaluation of men
with LUTS . There is a weak correlation between
symptoms (especially voiding symptoms) and BOO,
and no clinical or investigative features correlated
well with BOO demonstrated in pressure flow
studies . However, a combination of symptomatic
and urodynamic assessments is helpful. More
symptoms and low flow rates (<10 ml/s). Although
it is commonly used, uroflowmetry in general, and
Qmax in particular, lack specificity for a reliable
urodynamic diagnosis of the cause of LUTS .
Elevated PVR is associated with BOO, but the
relationship is not strong. Approximately 50% of
unobstructed elderly men have elevated PVR, and
30% of obstructed men do not. Pressure flow studies
have shown a clear association between classical
obstruction (high pressure/low flow) and more
positive surgical outcomes .
Clearly, urodynamically confirmed BOO and
voiding symptoms are more predictive of positive
outcomes of transurethral resection of the prostate
associated with severe
european urology 49 (2006) 651–659
(TURP) than are DO and storage symptoms. Machino
et al.  reported significantly greater symptomatic
improvements after TURP in men who had pre-
operative DO and BOO than in those with DO
without definitive obstruction. These authors also
reported that 60% of men with DO and equivocal
obstruction had persistent postoperative DO, com-
pared with 27% of those in whom DO and BOO were
confirmed preoperatively . In another study, 33%
(50/152) of men who had elective prostatectomies
continued to experience at least one OAB symptom
. These studies suggest that although BOO and
voiding symptoms may be treated surgically, they
may not be appropriate for men with DO and
predominant OAB symptoms.
In summary, OAB symptoms are highly prevalent
in men and adversely affect mental and physical
well-being. Prostatic pathology and coexisting OAB
symptoms are not always causally related, and
many men with OAB symptoms do not have BOO.
In fact, OAB symptoms may be more indicative of
bladder dysfunction such as DO than prostatic
conditions such as BOO and often persist after
prostatectomy or TURP. Thus, practitioners who
treat men with OAB symptoms should consider the
possible involvement of bladder dysfunction.
a1-Receptor antagonists and 5a-reductase
Despite the evidence that LUTS are not disease- or
condition-specific and hence, are not indicative of
BPH or BOO, the most commonly prescribed treat-
ments for LUTS, including OAB symptoms, target
doxazosin, terazosin, alfuzosin, and tamsulosin,
and 5a-reductase inhibitors such as finasteride
and dutasteride, possess favorable tolerability pro-
files and effectively treat voiding LUTS in many men
with BOO , but these agents may not be the most
effective treatments for the OAB component of male
The low density of detrusor a1-receptors in the
unobstructed bladder precludes significant direct
effects of a1-receptor antagonists on detrusor con-
tractility , and studies that investigated the
effects of BOO on a1-receptor expression and a1-
yielded conflicting results [38,39]. Nonetheless, 12
weeks of treatment with the a1-receptor antagonist
doxazosin failed to effectively treat LUTS in 65% of
men with BOO and DO . Furthermore, the ability
of histological changes mediated by 5a-reductase
inhibitors to directly attenuate DO and related OAB
symptoms has not been demonstrated. Evidence
are most likely to experience significant symptom
improvement with finasteride relative to placebo
, and symptomatic improvements may require
six months of treatment . However, a study of
dutasteride demonstrated that 5a-reductase inhibi-
tion reduced the severity of urinary symptoms in
men with baseline prostate volumes >30 ml .
Even though many men with LUTS do not have
of OAB symptoms after obstruction is relieved
pharmacologically or surgically, a recent study
demonstrated that most pharmacotherapies pre-
scribed for men with OAB symptoms target the
prostate rather than the bladder. Jumadilova et al.
 used a medical and pharmacy claims database
of more than 30 geographically diverse managed
care plans to identify men at least 18 who were
newly diagnosed with OAB. Of those without a BPH
diagnosis, 22% were prescribed BPH agents alone
(a1-receptor antagonists, 5a-reductase inhibitors),
11% received OAB agents alone (antimuscarinics),
and 6% received both. Sixty-one percent of these
men received neither therapy. Thus, 56% of men
with OAB symptoms without a BPH diagnosis who
received OAB or BPH agents were prescribed BPH
agents alone .
5. Focus on the bladder: antimuscarinics
Correlations between DO and OAB symptoms 
clearly indicate a multifactorial pathogenesis for
bladder dysfunction in the development of storage
LUTS. Changes in the properties of detrusor smooth
muscle may lead to enhanced excitability and result
in spontaneous detrusor contractions characteristic
of DO . Age-related changes that may contribute
to the development of DO include increases in
protrusion junctions, which may affect electrical
activity between smooth muscle cells . Changes
in unmyelinated, capsaicin-sensitive C-afferents
(which arebelieved to mediatesensationsof bladder
fullness) may also induce the urge to urinate at low
bladder volumes . A combination of these
factors, which are often combined with central
nervous system changes, may play a pivotal role.
Antimuscarinics block acetylcholine binding at
muscarinic receptors throughout the bladder, and
muscarinic receptor blockade inhibits detrusor
smooth muscle contraction . Although several
antimuscarinics are used to treat OAB, tolterodine
has been most extensively investigated for the
treatment of male OAB symptoms. The efficacy
european urology 49 (2006) 651–659
and safety of tolterodine were demonstrated in
recent trials, and suggest that antimuscarinic drugs
successfully treat OAB in men. For example, men
with OAB symptoms and UUI in the absence of
clinically significant BOO experienced significant
reductions in UUI episodes (?71%) compared with
placebo (?40%) after 12 weeks of treatment with
tolterodine extended release (ER) . Significant
reductions in total micturitions and urgency-related
micturitions were also observed in men with OAB
symptoms who received tolterodine ER treatment
for 12 weeks . These reports suggest that
antimuscarinic treatment safely ameliorates OAB
symptoms in men, but these were secondary
in prospective clinical trials.
Thirty-nine men with BPH and LUTS who had
failed a1-receptor antagonist therapy because of
adverse events or lack of efficacy demonstrated
significant reductions in micturition frequency,
nocturia, and AUA symptom scores after six months
of open-label treatment with tolterodine ER. A
significant increase in Qmaxand a decrease in PVR
were observed in the same study . These results
also support a role for antimuscarinics in the
treatment of male OAB; however, large, placebo-
controlled studies in men with OAB symptoms and
other LUTS are needed to demonstrate the efficacy
and safety of antimuscarinics in this population of
5.1. Antimuscarinic safety
There is concern that the inhibitory effect of
antimuscarinics on detrusor muscle contraction
could theoretically aggravate the voiding difficul-
ties of, or cause urinary retention in men with
OAB symptoms and possible BOO. However, little
evidence from clinical trials has supported the
concern. In a meta-analysis of randomized con-
trolled trials of antimuscarinics used to treat OAB,
only oxybutynin IR significantly increased the risk
of urinary retention compared with placebo .
Men with BOO and DO who received tolterodine
for 12 weeks demonstrated no change in Qmaxand
a reduction in detrusor pressure at Qmax. Tolter-
odine-treated men demonstrated a statistically
significant increase in PVR compared with placebo,
but whether this increase was clinically relevant is
unclear. In this study, tolterodine was not asso-
ciated with an increase in acute urinary retention
(AUR) that required catheterization . There was
also no incidence of AUR among 39 men with BPH
and LUTS who received open-label tolterodine ER
treatment for six months .
Historically, physicians have used increased PVR
and decreased Qmaxto identify patients at risk for
urinary retention. As noted earlier, PVR may
increase with BOO, but it represents detrusor
decompensation rather than prostatic obstruction
per se. Thus, urodynamic indicators of bladder
dysfunction are more predictive of urinary reten-
tion. For instance, in urodynamic studies of men
with LUTS and BOO, Te et al.  observed
significantly greater pressure of maximum detrusor
with a history of urinary retention than in those
without. Studies also suggest that men with bladder
decompensation (increased mass, decreased com-
pliance, cholinergic denervation) secondary to BOO
or neuropathy secondary to diabetic or peripheral
nerve injury may be at the greatest risk for
developing AUR . Poor compliance, one element
of the decompensatory response, is associated with
DO and BOO . In cases of advanced decom-
pensation secondary to severe, long-term obstruc-
tion, normal bladder function is unlikely to be
restored with a1-receptor antagonists or antimus-
5.2. Combination therapy
Despite the evidence that antimuscarinics may
safely and effectively treat OAB symptoms in men,
only 40% of men with OAB symptoms who receive
drug treatment are prescribed antimuscarinics .
Antimuscarinics can be safely combined with
a1-receptor antagonists to treat men with OAB
symptoms in the presence or absence of BOO
[23,55]. Recent studies suggest that antimuscari-
nic/a1-receptor antagonist combination treatments
may more effectively reduce male LUTS than
a1-receptor antagonists alone. Fifty men with
urodynamically confirmed BOO and DO received
tamsulosin alone. Significant reductions in max-
imum detrusor pressure during micturition and
maximum involuntary contraction pressure were
observed in men who received the combination
treatment for three months. These patients also
demonstrated significantly increased Qmax and
volume at first involuntary contraction, as well as
improvements in a quality of life measure. Changes
in maximum detrusor pressure, maximum invo-
luntary contraction pressure, and quality of life
measures did not reach statistical significance in
patients who received tamsulosin alone. There was
european urology 49 (2006) 651–659
Combinations of antimuscarinics and a1-receptor
antagonists have also proven effective for many
men who have failed treatment with a1-receptor
antagonists alone. Of 44 men with urodynamically
confirmed DO and BOO who failed three-month
treatment with doxazosin, 32 (73%) experienced
treatment with doxazosin and tolterodine. Thirty-
eight percent (6/16) of men with BOO alone also
experienced symptomatic improvements with the
improve with doxazosin alone . One patient in
each treatment group developed AUR that required
overnight catheterization (personal communica-
tion). Patients in the Athanasopoulos et al. 
and Lee et al.  studies were enrolled based, in
part, on the results of urodynamic evaluations. This
aspect limits the applicability of the results to
clinical practice, where patients are initially treated
based on symptoms rather than on urodynamic
endpoints. These studies suggest that antimuscari-
nics alone or in combination with a1-receptor
antagonists or, possibly, 5a-reductase inhibitors
may provide the most efficacious initial therapy
for men with OAB symptoms in the presence or
absence of prostatic pathology. To date, no studies
have evaluated the efficacy of combining antimus-
carinics with 5a-reductase inhibitors. However,
there is no evidence to suggest that 5a-reductase
inhibitors cannot also be safely combined with
antimuscarinics for the treatment of men with BPH
and OAB symptoms. Despite the success of combi-
nation therapy in clinical trials, Jumadilova et al. 
reported that only 8% of 4806 men with OAB
symptoms and a BPH diagnosis were prescribed a
A new approach to the treatment of male
Madersbacher  recently wrote that ‘‘Empirical
treatment is considered to be justified when the
symptoms are bothersome and have impact on the
quality of life, when treatments have no or low
morbidity and when early assessment of treatment
success is planned.’’ We
evaluationof the potential
approach to the initial treatment of male OAB
symptoms. Our approach would rely on careful
assessment of OAB symptoms, a physical exam-
ination, and urinalysis. An a1-receptor antagonist
would be prescribed if BOO is suspected based on
symptom assessment or uroflowmetry. In men
with enlarged prostates, a 5a-reductase inhibitor
may also improve symptoms. Adjuctive treatment
with an antimuscarinic would be considered for
patients with a normal urinalysis and no clinically
significant PVR whose symptoms do not respond
sufficiently to this therapy. This approach may
reduce the need forexpensive and
urodynamic procedures in patients whose OAB
symptoms respond to treatment with a1-receptor
antagonists, 5a- reductase inhibitors (where appro-
priate), antimuscarinics, or combination therapy.
Clinicians should use the terms OAB and LUTS to
describe symptoms and to use DO, BPH, and BOO
only when appropriate diagnostic procedures are
completed. We also emphasize that male OAB
symptoms are storage LUTS that may occur with
BPH or BOO without being caused by the prostatic
condition. OAB symptoms may be the results of
primary DO or DO secondary to BOO; thus, pharma-
cotherapies and surgical interventions that target
the prostate may not alleviate OAB symptoms.
antagonists, antimuscarinic agents relieve male
OAB symptoms without increasing the risk for
urinary retention in patients with comorbid BOO.
Successful initial treatment with antimuscarinics
alone or in combination with other agents may
preclude the need for urodynamic testing in men
with OAB symptoms. Urodynamics should be
reserved for cases resistant to therapy or performed
before a more invasive therapeutic intervention,
particularly in men with predominant storage
symptoms. At present, we must conclude that the
literature is based on pilot studies that use urody-
namic criteria for patient selection that do not
necessarily represent real life practice. Some of
these studies are not placebo controlled or are
not adequately powered. Combination therapy with
an anticholinergic and an a1-receptor antagonist
in men with OAB and with suspected BOO is an
interesting potential direction in pharmacotherapy
that requires testing in well-designed clinical trials
before it can be recommended for routine clinical
Disclosures: Dr. Chapple is a scientific consultant to
Pfizer, Schwarz Pharma, Astellas, Novartis and UCB.
Dr. Roehrborn has consulted with Pfizer Inc
regarding the development of anticholinergic drugs
in the treatment of men with lower urinary tract
symptoms, benign prostatic hyperplasia, and over-
european urology 49 (2006) 651–659
 Engstrom G, Henningsohn L, Steineck G, Leppert J. Self-
assessed health, sadness and happiness in relation to the
total burden of symptoms from the lower urinary tract.
BJU Int 2005;95:810–5.
 Hu TW, Wagner TH, Bentkover JD, et al. Estimated
economic costs of overactive bladder in the United States.
 Rosen R, Altwein J, Boyle P, et al. Lower urinary tract
symptoms and male sexual dysfunction: the Multina-
tional Survey of the Aging Male (MSAM-7). Eur Urol
 Abrams P, Cardozo L, Fall M, et al. The standardisation of
terminology in lower urinary tract function: report from
the standardisation sub-committee of the International
Continence Society. Urology 2003;61:37–49.
 Peters TJ, Donovan JL, Kay HE, et al. The International
Continence Society ‘‘Benign Prostatic Hyperplasia’’ Study:
the bothersomeness of urinary symptoms. J Urol 1997;
 Holtgrewe HL. Current trends in management of men
with lower urinary tract symptoms and benign prostatic
hyperplasia. Urology 1998;51:1–7.
 Abrams P. New words for old: lower urinary tract symp-
toms for ‘‘prostatism’’. BMJ 1994;308:929–30.
 Chatelain C, Denis L, Foo KT, Khoury S, McConnell J.
Benign Prostatic Hyperplasia. 5th International Con-
sultation on Benign Prostatic Hyperplasia; 2000; Paris,
 Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development
of human benign prostatic hyperplasia with age. J Urol
 Ameda K, Sullivan MP, Bae RJ, Yalla SV. Urodynamic
characterization of nonobstructive voiding dysfunction
in symptomatic elderly men. J Urol 1999;162:142–6.
 Ziada A, Rosenblum M, Crawford ED. Benign prostatic
hyperplasia: an overview. Urology 1999;53:1–6.
ing. BMJ 2001;322:106.
 Laniado ME, Ockrim JL, Marronaro A, Tubaro A, Carter SS.
Serumprostate-specificantigento predictthe presenceof
bladder outlet obstruction in men with urinary symp-
toms. BJU Int 2004;94:1283–6.
 Eckhardt MD, van Venrooij GE, Boon TA. Symptoms,
volunteers without and with LUTS and in patients with
LUTS suggestive of benign prostatic hyperplasia. Urology
 Abdel-AzizKF, LemackGE. Overactive bladderinthe male
patient: bladder, outlet, or both? Curr Urol Rep 2002;3:
 Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence
and burden of overactive bladder in the United States.
World J Urol 2003;20:327–36.
 Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff J,
Wein AJ. How widespread are the symptoms of an over-
active bladder and how are they managed? A population-
based prevalence study. BJU Int 2001;87:760–6.
 Temml C, Heidler S, Ponholzer A, Madersbacher S.
Prevalence of the overactive bladder syndrome by apply-
ing the International Continence Society definition. Eur
 Jolleys JV, Donovan JL, Nanchahal K, Peters TJ, Abrams P.
Urinary symptoms in the community: how bothersome
are they? Br J Urol 1994;74:551–5.
 Wein AJ. Bladder outlet obstruction—an overview. Adv
Exp Med Biol 1995;385:3–5.
 Knutson T, Edlund C, Fall M, Dahlstrand C. BPH with
coexisting overactive bladder dysfunction—an everyday
urological dilemma. Neurourol Urodyn 2001;20:237–47.
 Fusco F, Groutz A, Blaivas JG, Chaikin DC, Weiss JP.
Videourodynamic studies in men with lowerurinary tract
symptoms: a comparison of community based versus
referral urological practices. J Urol 2001;166:910–3.
 Lee JY, Kim HW, Koh JS, Suh HJ, Chancellor MB.
Comparison of doxazosin with or without tolterodine in
men with symptomatic bladder outlet obstruction and an
overactive bladder. BJU Int 2004;94:817–20.
 Hyman MJ, Groutz A, Blaivas JG. Detrusor instability in
men: correlation of lower urinary tract symptoms with
urodynamic findings. J Urol 2001;166:550–2.
 Sibley GN. The physiological response of the detrusor
muscle to experimental bladder outflow obstruction in
the pig. Br J Urol 1987;60:332–6.
 Steers W. Pathophysiology of overactive bladder and urge
urinary incontinence. Rev Urol 2002;4:S7–18.
 Lepor H, Machi G. Comparison of AUA symptom index in
unselected males and females between fifty-five and
seventy-nine years of age. Urology 1993;42:36–40.
 Terai A, Matsui Y, Ichioka K, Ohara H, Terada N,
Yoshimura K. Comparative analysis of lowerurinary tract
symptoms and bother in both sexes. Urology 2004;63:
 Romanzi LJ, Groutz A, Heritz DM, Blaivas JG. Involuntary
detrusor contractions: correlation of urodynamic data to
clinical categories. Neurourol Urodyn 2001;20:249–57.
 Araki I, Matsui M, Ozawa K, Takeda M, Kuno S. Relation-
ship of bladder dysfunction to lesion site in multiple
sclerosis. J Urol 2003;169:1384–7.
 Barry MJ, Cockett AT, Holtgrewe HL, McConnell JD,
Sihelnik SA, Winfield HN. Relationship of symptoms
of prostatism to commonly used physiological and
anatomical measures of the severity of benign prostatic
hyperplasia. J Urol 1993;150:351–8.
 Andersen JT, Nordling J, Walter S. Prostatism. I. The
correlation between symptoms, cystometric and urody-
namic findings. Scand J Urol Nephrol 1979;13:229–36.
 de la Rosette JJ, Witjes WP, Schafer W, et al. Relationships
obstruction: results from the ICS-‘‘BPH’’ study. Neurourol
 Machino R, Kakizaki H, Ameda K, et al. Detrusor instabil-
ity with equivocal obstruction: A predictor of unfavorable
symptomatic outcomes after transurethral prostatect-
omy. Neurourol Urodyn 2002;21:444–9.
 Abrams PH, Farrar DJ, Turner-Warwick RT, Whiteside CG,
Feneley RC. The results of prostatectomy: a symptomatic
european urology 49 (2006) 651–659
 Tiwari A, Krishna NS, Nanda K, Chugh A. Benign prostatic
hyperplasia: an insight into current investigational med-
ical therapies. Expert Opin Investig Drugs 2005;14:1359–
 Goepel M, Wittmann A, Rubben H, Michel MC. Compar-
ison of adrenoceptor subtype expression in porcine and
human bladder and prostate. Urol Res 1997;25:199–206.
 Bouchelouche K, Andersen L, Alvarez S, Nordling J,
Bouchelouche P. Increased contractile response to pheny-
lephrine in detrusor of patients with bladder outlet
obstruction: effect of the alpha1A and alpha1D-adrenergic
receptor antagonist tamsulosin. J Urol 2005;173:657–61.
 Nomiya M, Yamaguchi O. A quantitative analysis of
mRNA expression of alpha 1 and beta-adrenoceptor sub-
types and their functional roles in human normal and
obstructed bladders. J Urol 2003;170:649–53.
 Boyle P, Gould AL, Roehrborn CG. Prostate volume pre-
dicts outcome of treatment of benign prostatic hyperpla-
sia with finasteride: meta-analysis of randomized clinical
trials. Urology 1996;48:398–405.
 Tenover JL, Pagano GA, Morton AS, Liss CL, Byrnes CA.
Efficacy and tolerability of finasteride in symptomatic
benign prostatic hyperplasia: a primary care study.
Primary Care Investigator Study Group. Clin Ther 1997;
 Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G.
Efficacy and safety of a dual inhibitor of 5-alpha-reduc-
tase types 1 and 2 (dutasteride) in men with benign pro-
static hyperplasia. Urology 2002;60:434–41.
 Jumadilova Z, Harris H, del Aguila M, Wagner S,
Boccuzzi S, Bavendam T. Agent selection for overactive
bladder patients with and without documented comorbid
benign prostatic hyperplasia (Read By Title). Presented at:
International Continence Society; Aug 28–Sept 2, 2005;
 Brading A. A myogenic basis for the overactive bladder.
 Mostwin JL. Pathophysiology: the varieties of bladder
overactivity. Urology 2002;60:22–6.
 Reynard JM. Does anticholinergic medication have a role
for men with lower urinary tract symptoms/benign
urodynamicanalysisof 152 patients.J Urol
prostatic hyperplasia either alone or in combination with
other agents? Curr Opin Urol 2004;14:13–6.
 Roehrborn CG, Guan Z, Wang JT, Rovner ES, Kaplan SA.
Efficacy and safety of tolterodine in male patients with
overactive bladder and urinary incontinence. Presented
at: Society for Urodynamics and Female Urology; 2005;
 Marschall-Kehrel D, Abrams P, Guan Z, Wang JT, Hussian
I. Gender analysis of data from two 12-week randomized
controlled trials of tolterodine: tolterodine reduces over-
active bladder-related nocturnal frequency in men and
women with overactive bladder. Eur Urol 2005;4:61.
 Kaplan SA, Walmsley K, Te AE. Tolterodine extended
release attenuates lower urinary tract symptoms in
men with benign prostatic hyperplasia. J Urol 2005;
 Chapple C, Khullar V, Gabriel Z, Dooley JA. The effects of
antimuscarinic treatments in overactive bladder: A sys-
tematic review and meta-analysis. Eur Urol 2005;48:5–26.
and tolerability of tolterodine for the treatment of over-
active bladder in men with bladder outlet obstruction. J
 Te AE, Ghafar MA, Merriweather T, Volpe M, Ikeguchi E,
Kaplan SA. Nomogram and urodynamic predictors of
urinary retention in men with BPH and bladder outlet
obstruction. J Urol 2001;165 (Suppl):267.
N, et al. Mechanisms of bladder smooth-muscle hyper-
trophy and decompensation: lessons from normal devel-
opment and the response to outlet obstruction. World J
 Sullivan MP, Yalla SV. Detrusor contractility and compli-
ance characteristics in adult male patients with obstruc-
tive and nonobstructive voiding dysfunction. J Urol 1996;
 Athanasopoulos A, Gyftopoulos K, Giannitsas K, Fisfis J,
Perimenis P, Barbalias G. Combination treatment with an
alpha-blocker plus an anticholinergic for bladder outlet
obstruction: a prospective, randomized, controlled study.
J Urol 2003;169:2253–6.
 Madersbacher H. Overactive bladder: a clinical entity or a
marketing hype? Eur Urol 2005;47:273–6.
european urology 49 (2006) 651–659
Vincenzo Ficarra, Department of Urology,
University of Verona, Italy
Lower urinary tract symptoms (LUTS) cannot be
used to make a definitive diagnosis . In men with
LUTS, the definitions of benign prostatic hyperpla-
sia (BPH) and bladder outlet obstruction (BOO)
require histological and urodynamic confirma-
tions, respectively. Although voiding and postmic-
turition symptoms may be related to BOO caused
by benign prostatic enlargement/BPH, a relevant
percentage of patients also experience storage
In this review, Chapple and Roehrborn highlight
that overactive bladder (OAB) symptoms are a
subset of storage LUTS that may be caused by a
poorly functioning detrusor rather than by pro-
static pathology. Specifically, OAB symptoms may
be the results of primary or secondary BOO or
detrusor overactivity (DO), but can also occur
because of other forms of urinary dysfunction.
An attractive possibility is that urgency might be
european urology 49 (2006) 651–659 Download full-text
related to the activation of non-detrusor muscari-
nic receptors, localised on urothelial or interstitial
cells, in the absence of DO . That explains
why medical or surgical therapies that target the
prostate may not improve storage symptoms. The
logical consequence of the shifted paradigm that
focuses on the bladder is the potential use of
antimuscarinic drugs, alone or in combination
with a1-receptor antagonists, in patients with
bothersome OAB symptoms. This is clearly an
interesting expert opinion that is supported by two
recent studies that investigated the role of tolter-
odine in combination with tamsulosin  or
doxazosin  in men withBOO. Those pilot studies,
which analysed fewer than 100 patients, demon-
strated favourable preliminary results in terms of
both efficacy and safety. Specifically, tolterodine
was not associated with an increased risk of
urinary retention. This issue could be explained
by considering that antimuscarinics act mainly
during the storage phase, while their effects
decrease during the voiding phase when a massive
release of acetylcholine is present .
The results obtained in the pilot studies that
combined tolterodine and a1-receptor antagonists
can be generalized only to patients with urodyna-
mically confirmed DO and BOO. Those patients are
different from those described in the scenario of
the proposed new ‘‘empirical’’ approach to the
treatment of OAB symptoms in patients with LUTS
that are suggestive of BPH. Antimuscarinic drugs
are proposed for the patients with normal urina-
lysis, absent postvoid residual and storage symp-
toms, who do not respond sufficiently to a1-
receptor antagonists, regardless of an invasive
The new pharmacological approach to the
treatment of OAB in patients with suspected BOO
might be wise advice, based on a valid rationale. Its
application in real-life practice, however, has to be
based on larger and well-designed randomised
controlled trials, which are still lacking.
terminology of lower urinary tract function: report from
the standardization sub-committee of the International
Continence Society. Neurol Urodyn 2002;21:167–78.
 Reynard JM. Does anticholinergic medication havea role
for men with lower urinary tract symptoms/benign pro-
static hyperplasia either alone or in combination with
other agents? Curr Opin Urol 2004;14:13–6.
 Andersson KE. Antimuscarinics for treatment of over-
active bladder. Lancet Neurol 2004;3:46–53.
 Lee JY, Kim HK, Koh JS, et al. Comparison of doxazosin
with or without tolterodine in men with symptomatic
bladder outlet obstruction and an overactive bladder.
BJU Int 2004;94:817–20.
 Athanasopoulos A, Gyftopoulos K, Giannitsas K, et al.
Combination treatment with an alpha-blocker plus an
anticholinergic for bladder outlet obstruction: a pros-
pective, randomised, controlled study. J Urol 2003;169: