1. Management of Male OAB; Current Status in Japan
Department of Urology
University of Occupational and Environmental Health, Japan
Hisae NISHII

2. Lower Urinary Tract Symptoms
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

3. Overactive Bladder (OAB)
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.
BPE
BOO
Histologic BPH
LUTS

5. Epidemiology-Europe EU SIFO Study US NOBLE Study Over 40y/o 16.6% OAB
Male
Female
40-44
45-49
50-54
45-59
60-64
65-69
70-74
75+ 5 10 15 20 25 30 35 40 45
　(%)
EU SIFO Study
US NOBLE Study 40 35
Male
Female 30 25 20 15 10 5
18-24
25-34
35-44
45-54
55-64
65-74
75+
Age ( y/o)
Age (y/o)
Over 40y/o % 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 y/o
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
Imidafenacin$
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. Tamsulosin, 0.2mg/day, daily
　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

19. ** ** ** ** * IPSS-subscore 0 week 4weeks 3.5 3.2 2.9 2.9 2.2 2.2 1.8
4.0 **
0 week
4weeks
3.5 ** **
3.2
2.9
2.9
3.0
2.2
2.2 *
2.0
1.8
1.7
1.6
1.6
1.2
1.1
1.0
1.0
0.9
0.0
Sensation of imcomplete emptying
Daytime
Urinary
Frequency
Intermittency
Urgency
Slow stream
Straining
Nocturia
*：p<0.05、**：p<0.01（Wilcoxon signed-rank test）

20. 8.1 6.1 ** 10 8 6 4 2 OABSS 0 week 4 weeks **：p<0.01
（Wilcoxon signed-rank test）
0 week
4 weeks

21. ** ** ** OABSS-subscore 4週後 0 week 4weeks 3.2 2.3 2.1 1.8 1.5 1.0 1.0
4.0
4週後
0 week
4weeks **
3.2
3.0 **
2.3
2.1 **
2.0
1.8
1.5
1.0
1.0
1.0
0.9
0.0
Daytime
Urinary
Frequency
Nocturia
Urgency
Urgent incontinence
**：p<0.01（Wilcoxon signed-rank test）

22. 10 2 51 73 46 17 0 week 4 weeks OAB severity （％） 100 50
Severe（12≦OABSS） 10 2
Moderate（6≦OABSS≦11）
Mild（OABSS≦5） 51
n＝41 73 50 46 17
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. Naftpidil, 50mg/day, daily
IPSS ≧8　and QOL-Index ≧2
Prostate volume ≧15mL
Clinical BPH with OAB symptoms
0 week
12 weeks
Naftpidil, 50mg/day, daily
Evaluation
Evaluation
IPSS
0 week
12 weeks
***
***
***
***
***
***
***
n＝36
（Wilcoxon signed-rank test）
***：p＜0.001
Sensation of imcomplete emptying
Intermittency
Slow stream
Nocturia
Daytime
Urinary
Frequency
Urgency
Straining
Awa Y.,et al

25. Treatment of male OAB; Alpha1-adrenoceptor antagonists
Tamsulosin 0.2mg
Naftopidil 50mg
Naftopidil 75mg
Silodosin
Comparison of Tamsulosin, Natdopidil, Silodosin

26. Naftpidil, 75mg/day, daily
0 week
4 weeks
8 weeks
IPSS ≧8　and QOL-Index ≧2
Prostate volume ≧15mL
Clinical BPH with OAB symptoms
Naftpidil, 75mg/day, daily
Evaluation
Evaluation
Evaluation
IPSS
***
0 week
8 weeks
4 weeks
***
0 week
8 weeks
4 weeks
***
0 week
8 weeks
4 weeks
n＝31
Mean±S.D.
（Wilcoxon signed-rank test）
***：p＜0.0001
Storage
Symptom
Score
Voiding
Symptom
Score
Postmicturition
symptom
Score
Miyamoto K. et al. 2009

27. Voiding diary Daytime frequency Nighttime frequency Urgency （n＝17）
(回）
(点）
(点） ** ** * ** ** *
Mean±S.D.
（Wilcoxon signed-rank test）
**：p＜0.005
* ：p＜0.05
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. Silodosin, 8mg/day, daily
　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 ± 2.4–4.4 ± 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)  

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 Evaluation Tamsulosin 0.2mg/day, daily
　Entry criteria (n=90)
・Clinical BPH
・Over 50 y/o
・IPSS≥3
・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. ** ** ** ** 10 9 8 7 6 5 4 3 2 1 IPSS-subscore Total voiding score
Tamsulosin
Naftopidil
Silodosin

34. ** * * ** ** 8 7 6 5 4 3 2 1 IPSS-subscore Total storage score
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 plus an 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 plus an Anticholinergic for BPH with OAB (TAABO)
Combination treatment with Tamsulosin and Solifenacine
to OAB symptoms with BPH

38. Having OAB symptoms after 8 weeks Tamsulosin
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
N=214
Session Ⅰ
Session Ⅱ
Registration
－8weeks
4weeks
8weeks
12weeks
Age>50
Clinical BPH
IPSS more than8
QOL index more than 2
Qmax<15ml/sec
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

39. Combination therapy with Tamsulosin and propiverine 10mg significantly
Voiding diary
Average voiding time/24hr
Urgency *
P=0.0261
Tamsulosin
Tamsulosin+Propiverine 10mg
Tamsulosin+Propiverine 20mg **
P=0.0093
12wks（n）
12wks（mean±SD）
12wks（P）
Tamsulosin 46
10.3±2.9
0.004
+Propiverine10mg 49
9.4±2.3
<.0001
+Propiverine20mg 45
10.1±2.8
0.0074
12wks（n）
12wks（mean±SD）
12wks（P）
Tamsulosin 46
2.3±3.3
0.3024
+Propiverine10mg 49
1.0±1.5
<.0001
+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.

40. Total storage symptoms score in IPSS IPSS Q4 Urgency*
Tamsulosin
Tamsulosin+Propiverine 10mg
Tamsulosin+Propiverine 20mg *
P=0.0465 *
P=0.0252　
割付群
12週（n）
12週（mean±SD）
12週（P値）
Tamsulosin 47
5.7±3.7
0.0009
+Propiverine10mg 49
4.7±2.3
<.0001
+Propiverine20mg 45
4.5±2.8
割付群
12週（n）
12週（mean±SD）
12週（P値）
Tamsulosin 47
1.6±1.6
0.0195
+Propiverine10mg 49
0.9±1.0
<.0001
+Propiverine20mg 45
0.9±1.4
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
Tamsulosin
Tamsulosin+Propiverine 10mg
Tamsulosin+Propiverine 20mg
割付群
12週（n）
12週（mean±SD）
12週（P値）
Tamsulosin 47
3.9±4.2
0.029
+Propiverine10mg 49
3.5±3.1
0.0126
+Propiverine20mg 45
4.9±3.4
0.4823
割付群
12週（n）
12週（mean±SD）
12週（P値）
Tamsulosin 47
12.7±5.4
0.3259
+Propiverine10mg 49
12.2±6.2
0.8853
+Propiverine20mg 45
13.3±8.9
0.0667

42. The increase of residual urine volume was 20-25ml
P=0.0325　 *
Tamsulosin
Tamsulosin+Propiverine 10mg
Tamsulosin+Propiverine 20mg
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
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 plus an Anticholinergic for BPH with OAB (TAABO)
Combination treatment with Tamsulosin and Solifenacine
to OAB symptoms with BPH

45. Clinical BPH Tamsulosin 0.2mg/day, daiy Tamsulosin
OABSS
Q3 (Urgency)≧2 And OABSS≧3
Tamsulosin
Tamsulosin 0.2mg/day, daiy
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 5 20 4.0 10 4 3.4 15NS NS 5 ** 20
4.0 10 4
3.4 15
13.9
3.7
7.3 3
3.3
11.2
5.0 10
11.6
10.8
6.4 2 5
4.4 5 1
0 week
4 weeks
0 week
4 weeks
0 week
4 weeks
Tamsulosin + Solifenacine
Tamsulosin
Mean±SD
**：p＜0.01 *：p＜0.05　（Wilcoxon signed-rank test） 　

47. Qmax
Residual Urine Volume
（mL/s）
（mL） 30
150 NS NS NS NS 20
100
13.5
13.2
52.5
13.0
12.7
41.4 10 50
33.5
31.0
Mean±SD
paired t-test　
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 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

49. Treatment of OAB; Japanese guideline
OAB symptoms
Neurogenic disorders
Neurogenic
OAB
Nonneurogenic
Urinalysis and Residual Urine Volume
Hematuria
Pyuria
Normal urinalysis RV<50ml
Normal urinalysis RV≥50ml
UTI treatment
Primary treatment
ineffective
effective
Continue
Consultation to Urology specialist
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.