Management of Male OAB;

1
Management of Male OAB Current Status in Japan
Department of Urology University of Occupational
and Environmental Health, Japan
Hisae NISHII
2
Introduction LUTS
Lower Urinary Tract Symptoms LUTS
Voiding symptoms Slow stream Intermittency Heite
ncy Straining
Storage symptoms Daytime urinary
frequency Urgency Nocturia Urinary incontinence
Post micturition symptoms Sensation of
incomplete emptying Postmicturition dribble
3
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
4
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
• Storage symptoms often occur independently
• 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
• detrusor dysfunction.

LUTS
5
Epidemiology-Europe
US NOBLE Study
40
35
Male Female
30
25
20
15
10
5
0
18-24
25-34
35-44
45-54
55-64
65-74
75
Age ( y/o)
Age (y/o)
Over 40y/o 16.6 OAB
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
6
Epidemiology-Japan 2002
Daytime urinary frequency

y/o
7
Epidemiology-Japan 2002
Nighttime urinary frequency

y/o
8
Epidemiology-Japan 2002
Frequency of Urgency

y/o
9
Epidemiology-Japan 2002
Grade of Urgency

y/o
10
Epidemiology-Japan 2002
Social impact
11
Epidemiology-Japan 2002
Prevalence of OAB

y/o
12
Epidemiology-Japan 2002
Prevalence of OAB
12.4 of total
13
Epidemiology-Japan 2002
Patients cost for treatment of OAB
14
Epidemiology-Japan 2002
Percentage of OAB patients treated at clinic
y/o
15
Treatment of male OAB in JAPAN
Alpha1-adrenoceptor antagonists
Phosphodiesterase inhibitors
Prazosin Terazosin Urapidil Tamsulosin Naftopidil
Silodosin
Phytotherapeutic drug
Eviprostat
Antimuscarinic agents
Oxybutinin Propiverine Tolterodine Solifenacin Imi
dafenacin
Combination therapy
16
Treatment of male OAB A1-adrenoceptor
antagonists

• Tamsulosin 0.2mg
• Naftopidil 50mg
• Naftopidil 75mg
• Silodosin
• Comparison of Tamsulosin, Natdopidil, Silodosin

17
Treatment of male OAB Alpha1-adrenoceptor
antagonists

• Tamsulosin 0.2mg
• Naftopidil 50mg
• Naftopidil 75mg
• Silodosin
• Comparison of Tamsulosin, Natdopidil, Silodosin

18
0 week
4weeks
Entry criteria Male over 50y/o Clinical BPH
IPSS?8 OABSS?3 and Q3?2 QOL?2
Tamsulosin, 0.2mg/day, daily
Evaluation IPSS QOL Index OABSS
Evaluation IPSS QOL Index OABSS
Yoshida M et al., 2008
19
IPSS-subscore

4.0
0 week
4weeks

3.5


3.2
2.9
2.9
3.0
2.2
2.2

1.8
2.0
1.7
1.6
1.6
1.2
1.1
1.0
0.9
1.0
0.0
Sensation of imcomplete emptying
Urgency
Slow stream
Straining
Nocturia
Daytime Urinary Frequency
Intermittency
plt0.05?plt0.01(Wilcoxon signed-rank test)
20
OABSS

10
8.1
8
6.1
6
4
plt0.01 (Wilcoxon signed-rank test)
2
0
0 week
4 weeks
21
OABSS-subscore
4.0
4??
0 week
4weeks

3.2

3.0
2.3
2.1

2.0
1.8
1.5
1.0
1.0
0.9
1.0
0.0
Urgency
Nocturia
Urgent incontinence
Daytime Urinary Frequency
plt0.01(Wilcoxon signed-rank test)
22
OAB severity
()
100
Severe(12?OABSS)
10
2
Moderate(6?OABSS?11)
Mild(OABSS?5)
51
n41
73
50
46
17
0
0 week
4 weeks
23
Treatment of male OAB Alpha1-adrenoceptor
antagonists

• Tamsulosin 0.2mg
• Naftopidil 50mg
• Naftopidil 75mg
• Silodosin
• Comparison of Tamsulosin, Natdopidil, Silodosin

24
0 week
12 weeks
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







n36 (Wilcoxon signed-rank test) plt0.001
Sensation of imcomplete emptying
Intermittency
Slow stream
Nocturia
Daytime Urinary Frequency
Urgency
Straining
Awa Y.,et al.. 2008
25
Treatment of male OAB Alpha1-adrenoceptor
antagonists

• Tamsulosin 0.2mg
• Naftopidil 50mg
• Naftopidil 75mg
• Silodosin
• Comparison of Tamsulosin, Natdopidil, Silodosin

26
0 week
8 weeks
4 weeks
IPSS ?8 and QOL-Index ?2 Prostate volume
?15mL Clinical BPH with OAB symptoms
Naftpidil, 75mg/day, daily
Evaluation
Evaluation
Evaluation
IPSS
n31 MeanS.D. (Wilcoxon signed-rank
test) plt0.0001
Storage Symptom Score
Postmicturition symptom Score
Voiding Symptom Score
Miyamoto K. et al. 2009
27
Voiding diary
Nighttime frequency (n17)
Urgency (n14)
Daytime frequency (n17)
(?)
(?)
(?)






MeanS.D. (Wilcoxon signed-rank
test) plt0.005 plt0.05
0 week
8 weeks
0 week
8 weeks
0 week
8 weeks
4 weeks
4 weeks
4 weeks
Miyamoto K. et al. 2009
28
Treatment of male OAB Alpha1-adrenoceptor
antagonists

• Tamsulosin 0.2mg
• Naftopidil 50mg
• Naftopidil 75mg
• Silodosin
• Comparison of Tamsulosin, Natdopidil, Silodosin

29
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
30
IPSS-subscore
No significant changes in the OABSS (4.4
2.44.4 2.6, p 0.897) Qmax (11.7 6.1 to
12.7 6.3, P 0.259) residual urine volume
(38.0 59.440.0 58.7, P 0.526)  
31
Treatment of male OAB Alpha1-adrenoceptor
antagonists

• Tamsulosin 0.2mg
• Naftopidil 50mg
• Naftopidil 75mg
• Silodosin
• Comparison of Tamsulosin, Natdopidil, Silodosin

32
0 week
12weeks
Entry criteria (n90) Clinical BPH Over 50
y/o IPSS3 Prostate volume 50ml Residual
urine volume 100ml
Tamsulosin 0.2mg/day, daily Naftopidil 50mg/day,
Daily Silodosin, 8mg/day, daily
Evaluation IPSS, QOL Index
Kikuchi Y et al. 2010
33
IPSS-subscore
Total voiding score
10

9
8
7
6
5


4

3
2
1
0
Tamsulosin
Naftopidil
Silodosin
34
IPSS-subscore
Total storage score
8


7
6

5

4

3
2
1
0
Tamsulosin
Naftopidil
Silodosin
35
Treatment of male OAB Alpha1-adrenoceptor
antagonists

• Tamsulosin 0.2mg
• Naftopidil 50mg
• Naftopidil 75mg
• Silodosin
• Comparison of Tamsulosin, Natdopidil, Silodosin

36
Treatment of male OAB Combination therapy

• Trial of combination treatment with an
  Alpha-blocker plusan Anticholinergic for BPH
  with OAB (TAABO)
• Combination treatment with Tamsulosin and
  Solifenacine
• to OAB symptoms with BPH

37
Treatment of male OAB Combination therapy

• Trial of combination treatment with an
  Alpha-blocker plusan Anticholinergic for BPH
  with OAB (TAABO)
• Combination treatment with Tamsulosin and
  Solifenacine
• to OAB symptoms with BPH

38
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
N516
N214
Session ?
Session ?
Registration
4weeks
-8weeks
8weeks
12weeks
Agegt50 Clinical BPH IPSS more than8 QOL index
more than 2 Qmaxlt15ml/sec
Having OAB symptoms after 8 weeks
Tamsulosin Daitime frequency more than 8
times Urgency once/ 24 hrs at least Except
Qmaxlt5ml/sec, RVgt100ml
39

Voiding diary
Average voiding time/24hr
Urgency

P0.0261

P0.0093
12wks(n) 12wks(meanSD) 12wks(P)
Tamsulosin 46 10.32.9 0.004
Propiverine10mg 49 9.42.3 lt.0001
Propiverine20mg 45 10.12.8 0.0074
12wks(n) 12wks(meanSD) 12wks(P)
Tamsulosin 46 2.33.3 0.3024
Propiverine10mg 49 1.01.5 lt.0001
Propiverine20mg 45 1.43.0 0.0103
Combination therapy with Tamsulosin and
propiverine 10mg significantly decrease the
average voiding time and urgency times in voiding
diary.
40
Total storage symptoms score in IPSS
IPSS Q4 Urgency


P0.0465

P0.0252
??? 12?(n) 12?(meanSD) 12?(P?)
Tamsulosin 47 5.73.7 0.0009
Propiverine10mg 49 4.72.3 lt.0001
Propiverine20mg 45 4.52.8 lt.0001
??? 12?(n) 12?(meanSD) 12?(P?)
Tamsulosin 47 1.61.6 0.0195
Propiverine10mg 49 0.91.0 lt.0001
Propiverine20mg 45 0.91.4 lt.0001
Combination therapy with Tamsulosin and
propiverine 10mg significantly decrease the
storage symptoms scores and urgency score in IPSS.
41
Total voiding symptoms scores in IPSS
Qmax
??? 12?(n) 12?(meanSD) 12?(P?)
Tamsulosin 47 3.94.2 0.029
Propiverine10mg 49 3.53.1 0.0126
Propiverine20mg 45 4.93.4 0.4823
??? 12?(n) 12?(meanSD) 12?(P?)
Tamsulosin 47 12.75.4 0.3259
Propiverine10mg 49 12.26.2 0.8853
Propiverine20mg 45 13.38.9 0.0667
42

Residual urine volume
P0.0325

??? 12?(n) 12?(meanSD) 12?(P?)
Tamsulosin 47 38.039.6 0.0016
Propiverine10mg 49 59.655.3 lt.0001
Propiverine20mg 45 62.551.9 lt.0001
The increase of residual urine volume was 20-25ml
43

• 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.
44
Treatment of male OAB Combination therapy

• Trial of combination treatment with an
  Alpha-blocker plusan Anticholinergic for BPH
  with OAB (TAABO)
• Combination treatment with Tamsulosin and
  Solifenacine
• to OAB symptoms with BPH

45
OABSS Q3 (Urgency)?2 And OABSS?3
Tamsulosin 0.2mg/day, daiy
Tamsulosin
Clinical BPH
Tamsulosin 0.2mg/day, daiy Solifenacine
2.5mg/day, daily
More than 4 weeks
0 week
4 weeks
Evaluation IPSS, OABSS QOL index
Qmax Residual urine volume
Evaluation IPSS, OABSS QOL index
Qmax Residual urine volume
Kakizaki H et al., 2008
46
Total IPSS
QOL-index
OABSS
15
6

25


NS
5
NS

20
4.0
10
4
3.4
13.9
15
7.3
3.7
3
3.3
11.2
5.0
11.6
10
10.8
6.4
5
2
4.4
5
1
0
0
0 week
4 weeks
0 week
4 weeks
0 week
4 weeks
MeanSD plt0.01 plt0.05 (Wilcoxon signed-rank
test)
47
Qmax
Residual Urine Volume
(mL/s)
(mL)
30
150
NS
NS
NS
NS
20
100
13.2
13.5
52.5
41.4
13.0
12.7
10
50
33.5
31.0
MeanSD paired t-test
0
0
0 week
4 weeks
0 week
4 weeks
The OAB symptoms which were not released by
Tamsulosin monotherapy were significantly
released by adding solifenacine, without major
adverse effects.
48
Treatment of male OAB Combination therapy

• Trial of combination treatment with an
  Alpha-blocker plusan 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
49
Treatment of OAB Japanese guideline
Middle aged male likely with BPH are recommended
to be treated with alpha1-blocker or referred to
urology specialist.
50
Treatment of BPH Japanese guideline (2001)
Therapeutic options

• Alpha1-aderenoceptor antagonist
• Anti-andorogen drug
• Others Phytotherapeutic drugs

51
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

52
Resident Manual, Department of Urology, UOEH
53
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.