OVERACTIVE BLADDER IN MEN: SPECIAL CONSIDERATIONS FOR EVALUATION AND MANAGEMENT

OVERACTIVE BLADDER IN MEN: SPECIAL
CONSIDERATIONS FOR EVALUATION AND MANAGEMENT
ROGER R. DMOCHOWSKI
AND
DAVID R. STASKIN
ABSTRACT
Lower urinary tract symptoms (LUTS) in men may arise from a variety of underlying causes, including benign
prostatic hyperplasia. LUTS may have a significant component of storage symptoms (urgency, frequency,
urge incontinence) at presentation; however, the absence of overactive bladder (OAB) symptoms does not
necessarily imply pure outlet obstruction nor does their presence indicate the lack thereof. Symptomatic
correlates to urodynamic findings are high when considering isolated OAB symptoms. However, mixed
presentations or more overtly obstructive scenarios have less correlation with baseline symptom appraisal
instruments. The ideal approach for diagnosis and management is predicated on a graded approach, with
more invasive evaluation withheld for those men in whom presumptive therapy fails or who present with
associated complex symptoms and in whom a higher level of intervention is being considered. The increasing
incidence of LUTS with age implies a partial detrusor contribution, which must be considered in the overall
management schema. UROLOGY 60 (Suppl 5A): 56–63, 2002. © 2002, Elsevier Science Inc.
L
ower urinary tract symptoms (LUTS) in men
may be primarily obstructive or irritative in
composition or may be a blend of obstruction and
irritation. These symptoms have a significant effect
on quality of life, and when present in a moderateto-severe degree, they portend poorer overall quality of life and general health status compared with
the unaffected general population.1
Animal studies that have attempted to evaluate
the effect of lower urinary tract outlet obstruction
on storage and emptying parameters have demonstrated a variety of responses, although relatively
recently, in both the rat and minipig. Increasing
obstruction has been found to correlate with increasing bladder contractility until detrusor decompensation results. The chronicity by which
this process occurs in humans and the variable naFrom the Department of Urologic Surgery, Vanderbilt University
Medical Center, Nashville, Tennessee, USA (RRD); and Section of
Voiding Dysfunction, New York Presbyterian Hospital, Weill
Cornell Medical College, New York, New York, USA (DRS).
Roger R. Dmochowski is on the medical advisory board for
Lilly, Watson, and OMP Pharmaceuticals, and he is a study investigator funded by Surx, Lilly, Watson, Roche, and Schwartz.
David R. Staskin is a paid consultant to Ortho-McNeil,
Pfizer, Indevus, Kyowa, Yamanouchi, Roche, and Lilly.
Reprint requests: Roger R. Dmochowski, MD, Department of
Urologic Surgery, Room A1302, Medical Center North, Vanderbilt University Medical Center, Nashville, Tennessee 37232. Email: roger.dmochowski@mcmail.vanderbilt.edu
56
© 2002, ELSEVIER SCIENCE INC.
ALL RIGHTS RESERVED
ture of the symptoms associated with this spectrum of response imply the necessity of more than
superficial evaluation of men with LUTS. Most of
these men (approximately 70%) will be found to
have bladder outlet obstruction on subsequent
evaluation, and the incidence of outlet obstruction
is similar in all men no matter what the primary
complaint.2 Also, the incidence of LUTS increases
with age; voiding and storage symptoms increase,
with a more substantial increase in voiding abnormalities in men compared with women after the
fifth decade of life.3 This finding does not appear to
have Western cultural limitations, because the severity of voiding symptoms is also more frequent
and of greater magnitude in Japanese men compared with Japanese women ⬎50 years old.4
The evaluation and management of men with
symptoms consistent with overactive bladder
(OAB), including urinary urgency, frequency, and
urge urinary incontinence, hinge on the identification and assessment of the magnitude of concomitant lower urinary tract obstruction that may coexist with and be a cause (in part or in entirety) of
the presenting symptoms. This obstruction may
arise from benign prostatic hyperplasia (BPH), primary bladder neck dysfunction, or abnormal voiding dynamics on a learned or pathologic basis
(pseudodyssynergia or true dyssynergia). Chronic
prostatic pain syndromes (eg, abacterial chronic
prostatitis) and other pelvic floor dysfunctions can
0090-4295/02/$22.00
PII S0090-4295(02)01797-1
also present with a component of symptoms compatible with OAB. The complexity of the presenting symptoms and the variety of entities that exist
as possible differential diagnostic entities mandate
a thorough and diligent evaluation of the lower
urinary tract in men to plan optimal therapeutic
intervention. Evaluation is predicated on a complete assessment of voiding dynamics and is best
accomplished with urodynamic studies. These
studies should provide a complete representation
of filling characteristics, pressure and flow criteria,
sphincteric activity, and postvoid residual determination. LUTS are also heterogeneous in their
symptomatic impact. Urgency, nocturia, and hesitancy are most bothersome, whereas weak stream,
urgency, and frequency are the most prevalent in
pooled populations being evaluated for BPH.5
It is now well demonstrated that moderate-tosevere LUTS in men can result in urinary retention.
The incidence of retention in men with untreated
LUTS in community-based trials is 6.8 per 1000
during longitudinal follow-up of 4 years.6 If only
patients with moderate-to-severe symptoms are
considered, the rate of retention increases to 25 per
1000.7 Therefore, on the basis of these trials, untreated LUTS may place the patient at risk for potential clinical deterioration.
Optimal therapy for these patients may rely on
bladder outlet, bladder storage, or a combination
of outlet and storage therapy to achieve optimal
symptomatic response. However, reassessment
may be required in the case of partial symptomatic
response. The recognition of pelvic pain syndromes in men as contributory to urinary symptoms also requires therapy directed at this entity if
identified by screening evaluation.
EVALUATION OF MEN WITH LOWER
URINARY TRACT SYMPTOMS
Diagnostic evaluation of men with LUTS rests on
an initial estimation of subjective bother and objective data on bladder emptying. Because the occurrence of LUTS does not necessarily indicate
concomitant prostate enlargement and/or obstruction, specific modalities should be used to ascertain the potential for the etiologic role of these
entities.
Diary or voiding log completion by the patient
provides substantial evidence about the normal
urinary habits of that patient, including giving
some estimate of functional bladder capacity and
diurnal and nocturnal frequency. Frequency volume charts provide a strong correlation to cystometric capacities and are reasonably immune to the
effect of detrusor instability in men with LUTS.8
The symptomatic appraisal serves as a correlate to
UROLOGY 60 (Supplement 5A), November 2002
the diary and is assessed by any of several validated
LUTS questionnaires. The American Urologic Association symptom score for BPH (AUA-7) is most
commonly used in North America. However,
equally reproducible data can be obtained from the
International Prostate Symptom Score (IPSS), International Continence Society (ICS)-BPH, and
Danish Prostate Symptom Score (DAN-PSS-1)
scales. General quality-of-life instruments are less
useful, although they do provide incidence assessments that are reproducible.9 Recent evaluation of
the ICS male inventory, which is a derivative of the
ICS-BPH, has shown sensitivity for both incidence
assessment and bother quantification. Interestingly, whereas the highest prevalence of symptoms
centered on voiding, the most bothersome were
those symptoms related to storage. Obviously,
bother is what matters to the patient, because the
mere presence of symptoms of obstruction and urgency is not perceived as problematic by the individual.10 Disappointingly, numerous studies have
failed to demonstrate diagnostic specificity for
global LUTS and identifiable bladder outlet obstruction.11,12
The urinary flow test, which measures peak urinary flow rate and urinary residual volume, has
been used as the objective testing modality for
screening purposes. This modality provides relatively reasonable correlation with obstruction but
may be misinterpreted in the presence of detrusor
hypocontractility or high-flow, high-pressure
voiding (as can be seen in early-phase outlet obstruction associated with detrusor compensatory
changes). However, approximately 88% of men
with peak flow rates of ⱕ10 mL/sec will be found
to be obstructed on urodynamic evaluation.13 Furthermore, in considering symptoms and flow rate,
approximately 1% of men in their fifth decade of
life and 13% in their eighth decade of life will have
combined peak urine flow (Qmax) rates of ⬍10 mL/
sec and IPSS values of ⬍7.14 Overall, therefore, 1%
of men ⬍50 years and 13% of men ⬍80 years will
be obstructed and asymptomatic.15
In considering men with reduced flow rates,
symptoms, and increased age, without urodynamic
evaluation, other parameters become independently predictive of the development of acute urinary retention. Roehrborn et al.,16 –18 in a metaanalysis of predictors of retention in pooled groups
of placebo patients from clinical trials of men with
LUTS undergoing active interventions (4300 patients), found prostate-specific antigen and prostate volume to be strong independent predictors of
urinary retention in men followed up longitudinally in clinical trials. The implications for inclusion of these measures during long-term management of BPH are significant.
57
Greater diagnostic specificity is obviously mandated before interventions with permanent connotations (eg, thermotherapy or transurethral resection of the prostate [TURP]) are considered. So,
the diagnostic paradigm continues to evolve.
LUTS IN YOUNG MEN
LUTS in younger men can arise from a multiplicity of causes, including chronic prostatitis,
prostatodynia, and discrete bladder outflow obstruction. Primary bladder neck dysfunction is a
common cause of LUTS in younger men, with or
without pelvic pain.19,20 Functional abnormalities
of striated sphincter relaxation may also occur, further obfuscating the patient’s presentation.21 Because of the bothersome nature of these symptoms,
a variety of metrics have been used to quantitate
symptom magnitude, including the AUA Symptom
Index (AUASI) and the IPSS. Many experts advocate urodynamic evaluation of these patients to assess voiding parameters and also (when combined
with fluoroscopy) to identify discrete areas of obstruction associated with causes, such as primary
bladder neck dysfunction.
In a study of 52 men with LUTS who were ⬍45
years, Nitti and Ficazzola,19 using videourodynamics and the AUASI, identified 3 distinct types of
bladder neck obstruction. Type 1 included men
with fluoroscopic evidence of focal obstruction or
narrowing at the bladder neck with classic highpressure, low-flow voiding parameters (as defined
by the Abrams-Griffiths nomogram). Type 2 had a
similar radiographic appearance with sustained detrusor contraction pressures of ⬎30 cm H2O associated with reduced flows. Type 3 had sustained
high-pressure voiding with delayed opening of
the bladder neck. All had similar bother on the
basis of AUASI; however, detrusor instability was
statistically more likely to be associated with highpressure voiding as seen in types 1 and 2. They
concluded that, although the symptomatic presentation was similar, the findings of the videourodynamics varied and that fluoroscopic evaluation was
additive in discerning these varied voiding patterns.19
Earlier studies by Norlen and Blaivas22 in 23
younger men with a variety of referral diagnoses,
including neurogenic and psychogenic voiding
dysfunction, also found comprehensive videourodynamics to be of value, identifying 16 members of
this group as having findings compatible with
bladder neck obstruction (narrowed bladder neck,
high detrusor voiding pressure). Likewise, Kaplan
et al.,20,23,24 using similar evaluation techniques,
identified this disorder in 31 of 34 patients referred
for refractory prostatitis. Yalla et al.21,25 also identified a group of patients with slowed relaxation of
the bladder neck in response to increased detrusor
58
pressure during the voiding event. These patients
were found to have periurethral striated muscle
extending to the bladder neck, which the clinicians
postulated could be responsible for a pseudoobstructive initiation of voiding, much like that
seen in the patients with type 3 obstruction described by Nitti and Ficazzola.19 Certainly, other
pathophysiologic explanations can be advanced
for the distinct entity of primary bladder neck obstruction, such as smooth muscle hyperplasia and
neurologic dysfunction (sympathetic or neurotransmitter induced).26 Also, the recently described relation between increased intraprostatic
pressures found in men with chronic pelvic pain
and the high correlation of these symptoms with
the inflammatory variant of this disorder would
also tend to implicate the possible exacerbating potential of outlet obstruction in these patients.27
Options for therapy in this population include
␣-blockade and transurethral incision, both of
which have demonstrated reasonable outcomes.
However, results are consistently more significant
and durable with incision of the bladder neck.28
Similarly, ␣-blockers have also been used successfully in men with chronic prostatitis syndromes.28
Pooled results indicate that most ␣-blockers have
similar efficacy, with increasing adverse effects as
dose is increased.29
Surgical therapy for primary bladder obstruction
has produced sustained results in young men with
primary bladder neck dysfunction. In all, 87%
overall improvement in symptoms, urinary flow
rate, and peak voiding pressures has been reported
with unilateral bladder neck incision at a minimal
follow-up time of 1 year in men with this diagnosis.28,30
For those men with functional pelvic floor dyssynergy, directed therapy for the pelvic floor may
produce substantive resolution of symptoms.
Symptomatic improvement in 83% of 35 men with
pseudodyssynergia of the striated sphincter has
been reported with combined behavioral and
biofeedback modulations.24
LUTS IN OLDER MEN
In older men, diagnostic concerns include detrusor hyperactivity, impaired contractility syndrome, detrusor failure, carcinoma of the prostate,
and, of course, BPH. Between 50% and 75% of men
with bladder outlet obstruction will have OAB
symptoms31; however, the converse is not true, although some studies have failed to reveal as high a
prevalence of detrusor overactivity with these
symptoms.32 Moreover, the absence of symptoms
in age-selected men with subsequent urodynamic
evidence of outlet obstruction further lends credence to the significant symptomatic contribution
that irritative complaints supply to global LUTS
UROLOGY 60 (Supplement 5A), November 2002
scores. Walker et al.,15 evaluating a group of 24
men with no urinary symptoms, found 13% with
unequivocal obstruction and another 29% with
equivocal criteria for obstruction. The evaluation
and treatment of older men, however, are hampered by the coexistent onset of age-related detrusor changes, which complicate interpretation of
screening evaluations. The incidence of OAB in
men increases with age, an effect seen in the absence of substantial change as documented on urodynamic evaluation.33–35 It is well documented
that there is a decrease in Qmax attendant with advancing age, which simply may represent increased frequency in this age group or may represent true complex myogenic and neurogenic
ultrastructural changes occurring in the bladder.36 –38 Madersbacher et al.39 have aptly demonstrated this decrease in flow in a cohort of urodynamically unobstructed men with adequate
bladder contraction. Reductions in urine flow to
10 mL/sec of Qmax were shown, with no discernible
obstruction in slightly ⬎60% of the study population.
Severely depressed flow rates, are, however,
more consistent with obstruction, with flow rates
⬍10 mL/sec associated with obstruction in 88% of
patients.40,41 In the same analysis, however, patients with flow rates between 10 and 14 mL/sec
(pressures generally considered to be in the equivocal range) showed essentially equivalent incidences of obstruction (57% obstructed vs 43% unobstructed). Therefore, standard threshold values
for normal and abnormal flow rates may not apply
in this group and also may not be representative of
any outflow impedance. Longitudinal studies of
men with untreated prostatic obstruction and men
with detrusor underactivity have revealed significant worsening of OAB symptoms over baseline in
the absence of discernible changes in these populations. Other urodynamic measures of outlet obstruction have also been used to assess symptomatic LUTS in older men with BPH. Sullivan and
Yalla42 assessed bladder contractility and compliance in a group of 168 men with obstructive and
nonobstructive voiding dysfunction (as defined by
pressure differential between detrusor and urethra). They identified a significant correlation between maximal isovolumetric detrusor contraction
in men with obstruction compared with men without obstruction, independent of detrusor instability. The lowest incidence of compliance abnormalities was seen in the unobstructed patients. The
investigators believed that the detrusor contractility changes represented a detrusor compensation
to obstruction. They also noted that detrusor reserve, as measured by contraction indices and
postvoid residual volume, was lowest in the patients with chronic retention and indicated detruUROLOGY 60 (Supplement 5A), November 2002
sor decompensation. The concept of sustained isovolumetric contraction (stop-flow testing) has
been shown to correlate with bladder outlet obstruction by other groups as well.43
LUTS correlate poorly with most urodynamic
findings. Hyman et al.2 were only able to correlate
urge incontinence with detrusor instability in 160
men with a mean age of 61 years who presented for
evaluation of urinary symptoms. No other symptom correlated with urodynamic diagnosis. Of 109
patients with overt bladder outlet obstruction determined by pressure and flow criteria, 50 (46%)
also had urodynamic evidence of detrusor instability. Similarly, in a group of 565 men with LUTS,
26% had significant residual volume (⬎20% functional capacity), 46% had instability, and 53% were
obstructed.44 These investigators also concluded
that the complexity of presentation of men with
LUTS precluded presumptive diagnosis on the basis of symptoms alone. The disparity between presenting symptoms and urodynamic findings has
also been seen in large groups of patients with
mixed symptoms. Fusco et al.45 evaluated 541 neurologically normal men with LUTS and found 69%
to have some element of obstruction. However,
within the obstructed group, 47% had detrusor instability, and an additional 10% demonstrated poor
bladder contractility, which, at least partially, was
contributory to the overall symptomatic presentation.
The autonomous development of OAB symptoms in the absence of obstructive components is
accompanied by mural changes in the bladder,
which are characteristically seen in aging bladders
and also in obstructed bladders. These changes include loss of detrusor muscle volume, decreased
neuronal density, and increased intramuscular fibrosis, implying a potentially similar pathophysiologic explanation arising from seemingly disparate
causes.36,37
In this population, the overall response to medical therapy is interesting. Although overall symptomatic relief is often attained with ␣-blocker ingestion in men with LUTS, whether they are
obstructed or unobstructed, persistent irritative
symptoms may continue and may worsen with
time. Witjes et al.46 found that medical ␣-blockade
provided symptomatic and urine flow rate improvements in men who were obstructed on the
basis of urodynamic investigation and also in those
who were not obstructed. Interestingly, no significant changes were seen in the peak voiding pressures in the unobstructed group, despite the symptomatic change. Gerber et al.47,48 showed similar
results with short-term (3-month) doxazosin use.
However, with longer follow-up (15 months) time,
symptoms again deteriorated toward baseline. The
combination of isometric detrusor contraction and
59
maximum urinary flow rate has also been shown to
be predictive of obstructive voiding dysfunction in
men with obstructive symptoms and has been advocated as a guide for directed intervention designed to ameliorate those symptoms. Comiter et
al.49 found that this combined value accurately
predicted obstruction in 141 (93%) of 151 symptomatic men with infravesical obstruction. Recent
evaluation of tamsulosin in men unequivocally obstructed on the basis of pressure-flow evaluation
has demonstrated significant decreases in peak
voiding pressures, with concomitant parallelism in
symptomatic response in the study population.
Surprisingly, men with no urodynamic evidence of
obstruction had a similar clinical response with
short-term (3-month) treatment protocols, again
underscoring the reasonability of restricting complex evaluation to those men who do not respond
to presumptive medical therapy.50 The role of
␣-blockade in stimulating prostatic apoptosis,
thereby producing clinical effect, is now gaining
currency in addition to its accepted smooth muscle
relaxation properties.51
Another subgroup of the older male population
that presents a diagnostic challenge is those men
who have had prior prostate intervention (such as
TURP). Altogether, 19% of men will have persistent OAB symptoms after TURP, an effect more
marked in men ⬎80 years old; of these, a significant number are often again treated with surgical
intervention.52 Abrams53 and Nitti et al.,30 in separate analyses, have shown that ⬍20% of these men
have any evidence of recurrent or persistent bladder outlet obstruction. Also, Thomas et al.54 have
recently shown that even in men who have had
resolution of OAB symptoms after TURP, 48 (83%)
of 58 experienced return of their symptoms at
long-term follow-up (mean, 12.6 years after surgery). They also found that even a few men with no
OAB symptoms preoperatively developed de novo
OAB (39 [48%] of 82). No correlation between age
and time since surgery was able to be made in this
cohort. Most of those men with OAB symptoms
preoperatively, who had initial symptomatic resolution after surgery, experienced recurrence of
their symptoms with time. Similar to previously
noted findings in men with untreated obstruction
or underactive detrusor function, OAB symptoms
in these patients worsened in the absence of any
definable urodynamic change. This occurred despite sustained improvement in peak voiding pressures compared with preoperative values (Qmax,
100 vs 45 cm H2O; P ⬍0.05). Others have noted
similar early resolution of detrusor instability after
TURP, although this is not a universal result in all
studies. Pressure flow studies are particularly useful in this population as a means to compare therapies. These studies are reproducible and sensitive
60
for persistent outlet obstruction and provide adequate discrimination from placebo interventions.55
Moreover, the degree of symptomatic and urodynamic improvement with various interventions for
BPH correlates with the magnitude of intervention,
further lending reasonability to the observational
value of urodynamics in the initial and subsequent
evaluation of BPH.14 The pressure flow analysis
also has reliability and minimal intratest variability.56 The role of ambulatory urodynamics may also
further elucidate occult diagnoses in men with
LUTS. Rosario et al.57 found that 24% of 69 men
with LUTS were reclassified by ambulatory studies
compared with findings on complex, nonambulatory study as to presence and degree of obstruction.
This finding suggests several issues. Surgical intervention clearly produces early symptomatic
benefit for irritative symptoms, which may only
partially be because of relief of obstruction. The
potential for some form of deafferentation being
accomplished by these procedures (eg, TURP or
any bladder neck and proximal urethral intervention), leading to improvement in OAB symptoms,
must also be considered. Finally, the disappointing
long-term benefit for symptoms must be weighed
against the extended longitudinal nature of this
study—the fact that presumably ongoing age-related changes continued to occur in these men and
that other factors had potentially become overt,
such as the occurrence of neurologic diseases or
other confounding variables likely because of the
elapsed time of study.
CONCLUSION
The presence of OAB symptoms in men is indicative of many possible origins. Straightforward
screening techniques (quality-of-life assessment,
flow rate, residual urine volume determination)
are useful first-line segregating instruments. However, failure of presumptive medical therapy (or
other targeted therapies) should instigate more
formal evaluation to identify subtle detrusor or
bladder outlet factors that may masquerade as
bladder outlet obstruction, OAB, or both. Both
younger and older men present with unique etiologic possibilities that should be assiduously investigated to initiate apropos salvage therapies. The
role of urinary tract evaluation, as provided by
complex urodynamics, is paramount for a successful diagnostic paradigm to be applied to these patients.
Further knowledge about long-term results of
therapy and about chronic lower urinary tract
changes experienced with aging has demonstrated
the necessity for careful discrimination of presenting OAB symptoms. This tenet is especially true for
UROLOGY 60 (Supplement 5A), November 2002
the older man but has merit also for the younger
man who may experience different pathologic insults with a similar symptomatic response.
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DISCUSSION FOLLOWING DR. DMOCHOWSKI’S
PRESENTATION
Alan J. Wein, MD (Philadelphia, PA): How many male
patients with symptoms of overactive bladder (OAB) do you
see?
Roger R. Dmochowski, MD (Nashville, TN): I think ⱖ60%
of my patients have storage abnormalities in terms of OAB–
like symptoms.
David R. Staskin, MD (New York, NY): If these patients are
not obstructed and ␣-blockers are not working centrally,
should you treat them with an anticholinergic agent? I think
choosing ␣-blockers versus anticholinergics is based on
whether there is an obstruction.
Dr. Wein: I would not treat an older man with an antimuscarinic without giving him an ␣-blocker.
Dr. Staskin: What about the men between 40 and 60 years
of age? They are treated differently from women in the same
age group, despite the fact that the chance that they are obstructed is very low.
Christopher R. Chapple, MD (Sheffield, England): Many
of these men between 40 and 60 years of age do have a bladder
62
neck obstruction or related symptoms. The additional factor,
of course, is that many of these people have a degree of prostatitis. We all see the younger men with bladder neck obstruction with prostatitis, and often, a very pressured lifestyle
seems to relate in some way. So, there is some potential benefit
for using a combination of an anticholinergic agent and an
␣-blocker. Then, of course, clouding the issue even further is
that men with bladder neck obstruction do not do very well
with ␣-blockers as a rule.
Joseph G. Ouslander, MD (Atlanta, GA): I think both
drugs, ␣-blockers and antimuscarinics, are problematic in
older patients with comorbidities. The ␣-blockers make these
people susceptible to falls, and with the antimuscarinics, it is
impossible to tell whether there is any significant degree of
obstruction that puts them at risk for bladder decompensation.
Dr. Wein: I know the type of patient you are talking about.
I tell those patients they need to ask their internist first
whether they can take an ␣-blocker.
UROLOGY 60 (Supplement 5A), November 2002