Management of Male OAB;
Current Status in Japan
Department of Urology
University of Occupational and Environmental Health, Japan
Hisae NISHII
Introduction; LUTS
Lower Urinary Tract Symptoms
LUTS
Storage symptoms
Daytime urinary
frequency
Urgency
Nocturia
Urinary incontinence
Voiding symptoms
Slow stream
Intermittency
Heitency
Straining
Post micturition
symptoms
Sensation of
incomplete emptying
Postmicturition
dribble
Introduction; OAB
Overactive Bladder (OAB)
Urgency, with or without urge(ncy) incontinence, usually with frequency
and nocturia
Frequency
Urgency
Urge
incontinence
OAB is a gender-independent, multifactorial process with local stuructual and
functional changes of the bladder, and also systemic medical co-morbidity
Introduction; Male OAB
• The treatment of male LUTS is complicated, because the storage and voiding
symptoms frequently coexist.
• Storage symptoms have stronger impact on QOL in men than voiding
symptoms, however, voiding symptoms are most
prevalent in male LUTS
Histologic BPH
• Storage symptoms often occur independently
BPE
of (Bladder outlet obstruction) BOO and
persist in many men despite
pharmacologic and surgical treatment.
• It is unclear whether storage symptoms
may develop secondary to BOO or
BOO
detrusor dysfunction.
LUTS
Epidemiology-Europe
(%)
EU SIFO Study
US NOBLE Study
40
45
40
35
30
Male
Female
35
30
Male
Female
25
20
25
20
15
15
10
10
5
5
0
40-44 45-49 50-54 45-59 60-64 65-69 70-74 75+
0
Age ( y/o)
Over 40y/o 16.6% OAB
18-24 25-34 35-44 45-54 55-64 65-74 75+
Age (y/o)
Over 18y/o
Male
16.0% OAB
Female 16.9% OAB
EPIC study
LUTS were highly prevalent in both men and women
to a similar extent in both sexes
storage LUTS men 51.3%, women 59.2%
voiding LUTS men 25.7%. women 19.5%
postmicturion LUTS men 16.9%, women 14.2%
Epidemiology-Japan 2002
Daytime urinary frequency
％
y/o
Epidemiology-Japan 2002
Nighttime urinary frequency
％
y/o
Epidemiology-Japan 2002
Frequency of Urgency
％
y/o
Epidemiology-Japan 2002
Grade of Urgency
％
y/o
Epidemiology-Japan 2002
Social impact
Epidemiology-Japan 2002
Prevalence of OAB
％
y/o
Epidemiology-Japan 2002
Prevalence of OAB
12.4％ of total
Epidemiology-Japan 2002
Patients’ cost for treatment of OAB
Epidemiology-Japan 2002
Percentage of OAB patients treated at clinic
y/o
Treatment of male OAB in JAPAN
Alpha1-adrenoceptor antagonists
Prazosin
Terazosin
Urapidil
Tamsulosin
Naftopidil
Silodosin
Antimuscarinic agents
Oxybutinin
Propiverine
Tolterodine
Solifenacin
Imidafenacin$
Combination therapy
Phosphodiesterase inhibitors
Phytotherapeutic drug
Eviprostat
Treatment of male OAB; A1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin
Treatment of male OAB; Alpha1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin
Entry criteria
・Male over 50y/o
・Clinical BPH
・IPSS≧8
・OABSS≧3 and
Q3≧2
・QOL≧2
0 week
4weeks
Tamsulosin, 0.2mg/day, daily
Evaluation
IPSS
QOL Index
OABSS
Evaluation
IPSS
QOL Index
OABSS
Yoshida M et al., 2008
IPSS-subscore
**
4.0
3.5
**
2.2
2.0
*
1.6
1.6
1.1
Sensation of
imcomplete
emptying
2.9
2.2
1.7
1.8
1.2
1.0
1.0
Daytime
Urinary
Frequency
Intermittency
4weeks
**
3.2
2.9
3.0
0.0
**
0 week
0.9
Urgency
Slow stream
Straining
Nocturia
*：p<0.05、**：p<0.01（Wilcoxon signed-rank test）
OABSS
**
10
8
8.1
6.1
6
4
2
**：p<0.01
（Wilcoxon signedrank test）
0
0 week
4 weeks
OABSS-subscore
4.0
3.2
**
04週後
week
4weeks
**
3.0
2.3
2.0
2.1
**
1.8
1.5
1.0
0.0
1.0
1.0
0.9
Daytime
Urinary
Frequency
Nocturia
Urgency
Urgent
incontinence
**：p<0.01（Wilcoxon signed-rank test）
OAB severity
（％）
100
10
2
Severe（12≦OABSS）
Moderate（6≦OABSS≦11）
51
50
73
46
17
0
0 week
4 weeks
Mild（OABSS≦5）
n＝41
Treatment of male OAB; Alpha1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin
12 weeks
0 week
IPSS ≧8 and QOL-Index ≧2
Prostate volume ≧15mL
Clinical BPH with OAB symptoms
Naftpidil, 50mg/day, daily
Evaluation
Evaluation
IPSS
0 week
***
12 weeks
***
Sensation of
imcomplete
emptying
***
***
***
***
***
n＝36
（Wilcoxon signed-rank test）
***：p＜0.001
Intermittency
Daytime
Urinary
Frequency
Slow stream
Nocturia
Urgency
Straining
Awa Y.,et al.. 2008
Treatment of male OAB; Alpha1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin
IPSS ≧8 and QOL-Index ≧2
Prostate volume ≧15mL
Clinical BPH with OAB symptoms
0 week
Naftpidil, 75mg/day, daily
Evaluation
IPSS
Evaluation
Evaluation
***
***
***
8 weeks
4 weeks
***
***
***
n＝31
Mean±S.D.
（Wilcoxon signedrank test）
***：p＜0.0001
Storage
Symptom
Score
Voiding
Symptom
Score
0 week 4 weeks 8 weeks
0 week 4 weeks 8 weeks
Postmicturition
symptom
Score
0 week 4 weeks 8 weeks
Miyamoto K. et al. 2009
Voiding diary
Daytime frequency
(回）
（n＝17）
Nighttime frequency
（n＝17）
(点）
（n＝14）
(点）
**
**
Urgency
*
**
**
*
Mean±S.D.
（Wilcoxon signed-rank test）
**：p＜0.005
* ：p＜0.05
0 week
8 weeks
4 weeks
0 week
8 weeks
4 weeks
0 week
8 weeks
4 weeks
Miyamoto K. et al. 2009
Treatment of male OAB; Alpha1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin
Entry criteria
・Clinical BPH
・Naftopidil or
Tamsulosin
treatment more
than 6 months
0 week
4weeks
12weeks
Silodosin, 8mg/day, daily
Evaluation
IPSS, QOL Index, OABSS,Qmax,
Residual urine volume
IPSS
Tanaka M et al. 2010
IPSS-subscore
No significant changes in the
OABSS (4.4 ± 2.4–4.4 ± 2.6, p = 0.897)
Qmax (11.7 ± 6.1 to 12.7 ± 6.3, P = 0.259)
residual urine volume (38.0 ± 59.4–40.0 ± 58.7, P = 0.526)
Treatment of male OAB; Alpha1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin
0 week
Entry criteria
(n=90)
・Clinical BPH
・Over 50 y/o
・IPSS≥3
・Prostate volume
≥50ml
・Residual urine
volume ≤100ml
12weeks
Tamsulosin 0.2mg/day, daily
Naftopidil 50mg/day, Daily
Silodosin, 8mg/day, daily
Evaluation
IPSS, QOL Index
Kikuchi Y et al. 2010
IPSS-subscore
Total voiding score
10
**
9
8
7
6
5
**
4
3
**
**
2
1
0
Tamsulosin
Naftopidil
Silodosin
IPSS-subscore
8
Total storage score
**
7
*
6
*
5
**
4
3
**
2
1
0
Tamsulosin
Naftopidil
Silodosin
Treatment of male OAB; Alpha1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin
Treatment of male OAB; Combination therapy
•Trial of combination treatment with an Alpha-blocker plus
an Anticholinergic for BPH with OAB (TAABO)
•Combination treatment with Tamsulosin and Solifenacine
to OAB symptoms with BPH
Treatment of male OAB; Combination therapy
•Trial of combination treatment with an Alpha-blocker plus
an Anticholinergic for BPH with OAB (TAABO)
•Combination treatment with Tamsulosin and Solifenacine
to OAB symptoms with BPH
Tamsulosin 0.2mg, 1C/day, daily
Tamsulosin 0.2mg
1C/day, daily. 8weeks
Tamsulosin 0.2mg, 1C/day, daily
Propiverine 10mg, 1T/day, daily
Tamsulosin 0.2mg, 1C/day, daily
Propiverine 20mg, 1T/day, daily
N=516
Session Ⅰ
Registration
－8weeks
Age>50
Clinical BPH
IPSS more than8
QOL index more than 2
Qmax<15ml/sec
N=214
Session Ⅱ
4weeks
8weeks
12weeks
Having OAB symptoms after 8 weeks Tamsulosin
Daitime frequency more than 8 times
Urgency once/ 24 hrs at least
Except Qmax<5ml/sec, RV>100ml
Voiding diary
Average voiding time/24hr
Urgency
P=0.0261
*
Tamsulosin
Tamsulosin+Propiverine 20mg
Tamsulosin+Propiverine 10mg
P=0.0093
12wks
（n）
12wks
（mean±SD）
12wks（P）
Tamsulosin
46
10.3±2.9
0.004
+Propiverine10mg
49
9.4±2.3
+Propiverine20mg
45
10.1±2.8
**
12wks
（n）
12wks
（mean±SD）
12wks（P）
Tamsulosin
46
2.3±3.3
0.3024
<.0001
+Propiverine10mg
49
1.0±1.5
<.0001
0.0074
+Propiverine20mg
45
1.4±3.0
0.0103
Combination therapy with Tamsulosin and propiverine 10mg significantly
decrease the average voiding time and urgency times in voiding diary.
Total storage symptoms score in IPSS
Tamsulosin
Tamsulosin+Propiverine 20mg
P=0.0465
IPSS Q4 Urgency
*
*
*
P=0.0252
Tamsulosin+Propiverine 10mg
割付群
12週
（n）
12週
（mean±SD）
12週（P値）
割付群
12週
（n）
12週
（mean±SD）
12週（P値）
Tamsulosin
47
5.7±3.7
0.0009
Tamsulosin
47
1.6±1.6
0.0195
+Propiverine10mg
49
4.7±2.3
<.0001
+Propiverine10mg
49
0.9±1.0
<.0001
+Propiverine20mg
45
4.5±2.8
<.0001
+Propiverine20mg
45
0.9±1.4
<.0001
Combination therapy with Tamsulosin and propiverine 10mg significantly
decrease the storage symptoms scores and urgency score in IPSS.
Total voiding symptoms scores in IPSS
Qmax
Tamsulosin
Tamsulosin+Propiverine 20mg
Tamsulosin+Propiverine 10mg
割付群
12週
（n）
12週
（mean±SD）
12週（P値）
割付群
12週
（n）
12週
（mean±SD）
12週（P値）
Tamsulosin
47
3.9±4.2
0.029
Tamsulosin
47
12.7±5.4
0.3259
+Propiverine10mg
49
3.5±3.1
0.0126
+Propiverine10mg
49
12.2±6.2
0.8853
+Propiverine20mg
45
4.9±3.4
0.4823
+Propiverine20mg
45
13.3±8.9
0.0667
Residual urine volume
* P=0.0325
Tamsulosin
Tamsulosin+Propiverine 20mg
Tamsulosin+Propiverine 10mg
割付群
12週
（n）
12週
（mean±SD）
12週（P値）
Tamsulosin
47
38.0±39.6
0.0016
+Propiverine10mg
49
59.6±55.3
<.0001
+Propiverine20mg
45
62.5±51.9
<.0001
The increase of residual urine volume was 20-25ml
•
Voiding times and urgency times in voiding diary, storage symptom scores and
urgency in IPSS were significantly decreased with combination therapy with
Tamsulosin and propiverine 10mg.
•
Voiding symptom scores in IPSS and Qmax in uroflowmetrty did not show any
significant difference between Tamsulosin single therapy and combination
therapy with Tamsulosin and propiverine.
•
Residual urine volume had tendency to increase in combination therapy group.
One case of urinary retention was reported in the combination therapy with
Tamsulosin and propiverine 20mg.
•
Adverse effects were observed in 7.6% (15/197) in combination therapy.
The combination therapy with Tamsulosin and Propiverine
10mg significantly decreased male OAB symptoms with BPH
without major adverse effects.
Treatment of male OAB; Combination therapy
•Trial of combination treatment with an Alpha-blocker plus
an Anticholinergic for BPH with OAB (TAABO)
•Combination treatment with Tamsulosin and Solifenacine
to OAB symptoms with BPH
OABSS
Q3 (Urgency)≧2 And
OABSS≧3
Clinical
BPH
Tamsulosin 0.2mg/day, daiy
Tamsulosin
More than 4 weeks
Evaluation
IPSS, OABSS
QOL index
Qmax
Residual urine volume
Tamsulosin 0.2mg/day, daiy
＋Solifenacine 2.5mg/day, daily
0 week
4 weeks
Evaluation
IPSS, OABSS
QOL index
Qmax
Residual urine volume
Kakizaki H et al., 2008
Total IPSS
25
6
**
NS
4
13.9
11.2
10
11.6
10.8
*
OABSS
**
**
4.0
10
3.4
3.7
7.3
3.3
5
2
6.4
5.0
4.4
5
0
3
15
NS
5
20
15
QOL-index
1
0 week
4 weeks
0
0 week
4 weeks
Mean±SD
**：p＜0.01 *：p＜0.05 （Wilcoxon signed-rank test）
0 week
4 weeks
Tamsulosin + Solifenacine
Tamsulosin
Qmax
Residual Urine Volume
（mL/s）
（mL）
30
150
NS
NS
NS
NS
20
10
0
100
13.5
13.2
13.0
12.7
0 week
4 weeks
50
0
41.4
52.5
33.5
31.0
Mean±SD
paired t-test
0 week
4 weeks
The OAB symptoms which were not released by Tamsulosin
monotherapy were significantly released by adding
solifenacine, without major adverse effects.
Treatment of male OAB; Combination therapy
•Trial of combination treatment with an Alpha-blocker plus
an Anticholinergic for BPH with OAB (TAABO)
•Combination treatment with Tamsulosin and Solifenacine
to OAB symptoms with BPH
Effective, but have to be careful of urinary retention or increase in residual
urine volume
Treatment of OAB; Japanese guideline
OAB symptoms
Middle aged male
likely with BPH are
recommended to be
treated with alpha1blocker or referred
to urology specialist.
Neurogenic disorders
Nonneurogenic
OAB
Neurogenic
OAB
Urinalysis and Residual Urine Volume
Hematuria
Pyuria
UTI
treatment
Normal urinalysis
RV<50ml
Normal urinalysis
RV≥50ml
Primary treatment
effective
Continue
Consultation to Urology specialist
ineffective
Treatment of BPH; Japanese guideline (2001)
Therapeutic options
•Alpha1-aderenoceptor antagonist
•Anti-andorogen drug
•Others; Phytotherapeutic drugs
Shift in the treatment of male OAB ?
• Alpha1-receptor antagonist for BOO
• Antimuscarinic agents for Non-responders
• 5alpha-reductase inhibitor for BPE
• Comination therapy Qmax ≥5ml/sec, RV ≤100ml
Resident Manual, Department of Urology, UOEH
Conclusions
• Lower urinary tract symptoms occur commonly in Japanese
population.
• Storage symptoms, in particular urgency and the symptoms
of OAB, are the most bothersome in male LUTS.
• Alpha1-adrenoceptor antagonist monotherapy improves OAB
symptoms in male patients.
• Combination therapy with alpha1-adrenoceptor antagonist
and antimuscarinic agents improve OAB symptoms in male
patients.