Aim: To verify if the efficacy of the triple therapy with tamsulosin, dutasteride, and imidafenacin (TDI) is influenced by any background characteristics in patients with overactive bladder (OAB). Methods: A subanalysis of data from the DIrecT study was conducted. Superiority of TDI over tamsulosin and dutasteride in terms of efficacy based on the Overactive Bladder Symptom Score (OABSS), total International Prostate Symptom Score (IPSS), IPSS quality of life index, and postvoid residual (PVR) was evaluated in binary subgroups. Results: In the treatment groups, there was a significant interaction of total OABSS with testosterone level (≥4.8 vs. <4.8 ng/mL, p = 0.043) and PVR (≥20 vs. <20 mL, p = 0.018). For the total IPSS, no significant interaction was found except for the IPSS QOL index. For the IPSS QOL index, a significant interaction was found with testosterone level (≥4.8 vs. <4.8 ng/mL, p < 0.0001) as well as with total IPSS and total OABSS. For the PVR, no significant interaction was found except with total OABSS. Conclusions: Triple therapy with TDI is suggested to be a therapeutic option for benign prostatic hyperplasia in patients with residual OAB symptoms refractory to tamsulosin and in patients with various background characteristics regardless of severity of OAB symptoms. Trial Registry No. UMIN 000011980.

1.
Yamanishi
T
,
Asakura
H
,
Seki
N
,
Tokunaga
S
.
A 52-week multicenter randomized controlled study of the efficacy and safety of add-on dutasteride and imidafenacin to tamsulosin in patients with benign prostatic hyperplasia with remaining overactive bladder symptoms (DIrecT study)
.
Low Urin Tract Symptoms
.
2019
;
11
(
3
):
115
21
. .
2.
Azadzoi
KM
,
Radisavljevic
ZM
,
Golabek
T
,
Yalla
SV
,
Siroky
MB
.
Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder
.
J Urol
.
2010
;
183
(
1
):
362
9
. .
3.
Yamanishi
T
,
Asakura
H
,
Seki
N
,
Tokunaga
S
.
Efficacy and safety of combination therapy with tamsulosin, dutasteride and imidafenacin for the management of overactive bladder symptoms associated with benign prostatic hyperplasia: a multicenter, randomized, open-label, controlled trial (DIrecT Study)
.
Int J Urol
.
2017
;
24
(
7
):
525
31
. .
4.
Karazindiyanoğlu
S
,
Cayan
S
.
The effect of testosterone therapy on lower urinary tract symptoms/bladder and sexual functions in men with symptomatic late-onset hypogonadism
.
Aging Male
.
2008
;
11
(
3
):
146
9
. .
5.
Hristov
KL
,
Parajuli
SP
,
Provence
A
,
Petkov
GV
.
Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels
.
Am J Physiol Renal Physiol
.
2016
;
311
(
6
):
F1253
9
. .
6.
Koritsiadis
G
,
Stravodimos
K
,
Mitropoulos
D
,
Doumanis
G
,
Fokitis
I
,
Koritsiadis
S
,
Androgens and bladder outlet obstruction: a correlation with pressure-flow variables in a preliminary study
.
BJU Int
.
2008
;
101
(
12
):
1542
6
. .
7.
Bravo
G
,
Massa
H
,
Rose′Meyer
R
,
Chess-Williams
R
,
McDermott
C
,
Sellers
DJ
.
Effect of short-term androgen deficiency on bladder contractility and urothelial mediator release
.
Naunyn Schmiedebergs Arch Pharmacol
.
2017
;
390
(
5
):
547
56
. .
8.
Bonilla-Becerra
SM
,
de Oliveira
MG
,
Calmasini
FB
,
Rojas-Moscoso
JA
,
Zanesco
A
,
Antunes
E
.
Micturition dysfunction in four-month old ovariectomized rats: effects of testosterone replacement
.
Life Sci
.
2017
;
179
:
120
9
. .
9.
Greco
EA
,
Spera
G
,
Aversa
A
.
Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences
.
Eur Urol
.
2006
;
50
(
5
):
940
7
. .
10.
Zhou
Y
,
Ling
EA
.
Neuronal nitric oxide synthase in the neural pathways of the urinary bladder
.
J Anat
.
1999
;
194
(
Pt 4
):
481
96
. .
11.
Hotta
Y
,
Kataoka
T
,
Kimura
K
.
Testosterone deficiency and endothelial dysfunction: nitric oxide, asymmetric dimethylarginine, and endothelial progenitor cells
.
Sex Med Rev
.
2019
;
7
(
4
):
661
8
. .
12.
Persson
K
,
Igawa
Y
,
Mattiasson
A
,
Andersson
KE
.
Effects of inhibition of the L-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro
.
Br J Pharmacol
.
1992
;
107
(
1
):
178
84
. .
13.
Schatzl
G
,
Brössner
C
,
Schmid
S
,
Kugler
W
,
Roehrich
M
,
Treu
T
,
Endocrine status in elderly men with lower urinary tract symptoms: correlation of age, hormonal status, and lower urinary tract function. The Prostate Study Group of the Austrian Society of Urology
.
Urology
.
2000
;
55
(
3
):
397
402
.
14.
Mitterberger
M
,
Pallwein
L
,
Gradl
J
,
Frauscher
F
,
Neuwirt
H
,
Leunhartsberger
N
,
Persistent detrusor overactivity after transurethral resection of the prostate is associated with reduced perfusion of the urinary bladder
.
BJU Int
.
2007
;
99
(
4
):
831
5
. .
15.
Daly
DM
,
Nocchi
L
,
Liaskos
M
,
McKay
NG
,
Chapple
C
,
Grundy
D
.
Age-related changes in afferent pathways and urothelial function in the male mouse bladder
.
J Physiol
.
2014
;
592
(
3
):
537
49
. .
16.
Apostolidis
A
,
Jacques
TS
,
Freeman
A
,
Kalsi
V
,
Popat
R
,
Gonzales
G
,
Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity
.
Eur Urol
.
2008
;
53
(
6
):
1245
53
. .
17.
Chung
SD
,
Liu
HT
,
Lin
H
,
Kuo
HC
.
Elevation of serum C-reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder
.
Neurourol Urodyn
.
2011
;
30
(
3
):
417
20
. .
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.