Abstract
Background: There is limited research into the efficacy and safety of tadalafil combined with tamsulosin for the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), with or without erectile dysfunction (ED). Therefore, we aimed to investigate the efficacy and safety of combination therapy compared to that of monotherapy. Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang Data Service Platform, and ClinicalTrials.gov to identify eligible studies. A total of 639 articles were retrieved, of which 12 were randomized controlled trials (RCTs) published as of February 2023 and included in this meta-analysis. Results: After screening 639 articles, 12 RCTs including 1,531 subjects were considered eligible for the meta-analysis. The results showed that the total International Prostate System Score (total IPSS), maximum flow rate (Qmax), and quality of life (QoL) in tadalafil combined with tamsulosin were significantly better than those in monotherapy. Compared with tadalafil monotherapy, combination therapy mainly improved IPSS voiding. As for postvoid residual urine (PVR), the combination therapy did not improve PVR compared to the tadalafil group, but significantly improved PVR compared to the tamsulosin group. For the International Index of Erectile Function (IIEF), the curative effect of the combined group was better than that of the tamsulosin group but not better than that of the tadalafil group. In terms of safety, the adverse reactions (AEs) in the combined treatment group were significantly higher than those in the monotherapy group. None of the 12 RCTs reported serious adverse events. Conclusions: Tadalafil combined with tamsulosin was more effective in the treatment of male LUTS/BPH, with or without ED, on the improvement of total IPSS, QoL, and Qmax. However, the benefits of combination therapy for ED remain unclear. However, combination therapy seemed to have a higher incidence of adverse reactions.
Journal Section:
Research Article
References
1.
Lerner
LB
, McVary
KT
, Barry
MJ
, Bixler
BR
, Dahm
P
, Das
AK
et al. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA GUIDELINE PART I-initial work-up and medical management
. J Urol
. 2021
;206
(4
):806
–17
.2.
Rosen
RC
, Wei
JT
, Althof
SE
, Seftel
AD
, Miner
M
, Perelman
MA
et al. Association of sexual dysfunction with lower urinary tract symptoms of BPH and BPH medical therapies: results from the BPH Registry
. Urology
. 2009
;73
(3
):562
–6
.3.
Singam
P
, Hong
GE
, Ho
C
, Hee
TG
, Jasman
H
, Inn
FX
et al. Nocturia in patients with benign prostatic hyperplasia: evaluating the significance of ageing, co-morbid illnesses, lifestyle and medical therapy in treatment outcome in real life practice
. Aging Male
. 2015
;18
(2
):112
–7
.4.
Mirone
V
, Sessa
A
, Giuliano
F
, Berges
R
, Kirby
M
, Moncada
I
. Current benign prostatic hyperplasia treatment: impact on sexual function and management of related sexual adverse events
. Int J Clin Pract
. 2011
;65
(9
):1005
–13
.5.
Welliver
C
, Feinstein
L
, Ward
JB
, Fwu
CW
, Kirkali
Z
, Bavendam
T
et al. Trends in lower urinary tract symptoms associated with benign prostatic hyperplasia, 2004 to 2013: the urologic diseases in America project
. J Urol
. 2020
;203
(1
):171
–8
.6.
van Dijk
MM
, de la Rosette
JJ
, Michel
MC
. Effects of alpha(1)-adrenoceptor antagonists on male sexual function
. Drugs
. 2006
;66
(3
):287
–301
.7.
Gacci
M
, Andersson
KE
, Chapple
C
, Maggi
M
, Mirone
V
, Oelke
M
et al. Latest evidence on the use of phosphodiesterase type 5 inhibitors for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia
. Eur Urol
. 2016
;70
(1
):124
–33
.8.
Andersson
KE
, de Groat
WC
, McVary
KT
, Lue
TF
, Maggi
M
, Roehrborn
CG
et al. Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action
. Neurourol Urodyn
. 2011
;30
(3
):292
–301
.9.
Chapple
CR
, Roehrborn
CG
, McVary
K
, Ilo
D
, Henneges
C
, Viktrup
L
. Effect of tadalafil on male lower urinary tract symptoms: an integrated analysis of storage and voiding international prostate symptom subscores from four randomised controlled trials
. Eur Urol
. 2015
;67
(1
):114
–22
.10.
Vignozzi
L
, Gacci
M
, Cellai
I
, Morelli
A
, Maneschi
E
, Comeglio
P
et al. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS
. Prostate
. 2013
;73
(13
):1391
–402
.11.
Giuliano
F
, Ückert
S
, Maggi
M
, Birder
L
, Kissel
J
, Viktrup
L
. The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia
. Eur Urol
. 2013
;63
(3
):506
–16
.12.
Hutton
B
, Salanti
G
, Caldwell
DM
, Chaimani
A
, Schmid
CH
, Cameron
C
et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations
. Ann Intern Med
. 2015
;162
(11
):777
–84
.13.
Higgins
JP
, Altman
DG
, Gøtzsche
PC
, Jüni
P
, Moher
D
, Oxman
AD
et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials
. BMJ
. 2011
343
d5928
.14.
Dell’Atti
L
, Cuneo
A
. Use of 5-phosphodiesterase inhibitors in patients with luts secondary to bph: our experience and review of the literature
. Urologia
. 2013
;80
(4
):307
–16
.15.
Karami
H
, Hassanzadeh-Hadad
A
, Fallah-Karkan
M
. Comparing monotherapy with tadalafil or tamsulosin and their combination therapy in men with benign prostatic hyperplasia: a randomized clinical trial
. Urol J
. 2016
;13
(6
):2920
–6
.16.
Kim
SW
, Park
NC
, Lee
SW
, Yang
DY
, Park
JK
, Moon
DG
et al. Efficacy and safety of a fixed-dose combination therapy of tamsulosin and tadalafil for patients with lower urinary tract symptoms and erectile dysfunction: results of a randomized, double-blinded, active-controlled trial
. J Sex Med
. 2017
;14
(8
):1018
–27
.17.
Nagasubramanian
S
, John
NT
, Antonisamy
B
, Mukha
RP
, Jeyachandra Berry
CS
, Kumar
S
et al. Tamsulosin and placebo vs. tamsulosin and tadalafil in male lower urinary tract symptoms: a double-blinded, randomised controlled trial
. BJU Int
. 2020
;125
(5
):718
–24
.18.
Nasef
OM
, Ebid
AEE
, Koritenah
AK
. Effect of tadalafil add-on therapy in patients with lower urinary tract symptoms due to benign prostatic hyperplasia refractory to tamsulosin monotherapy: randomized, controlled trial
. Al-Azhar Med J
. 2021
;50
(3
):1659
–70
.19.
Regadas
RP
, Reges
R
, Cerqueira
JB
, Sucupira
DG
, Josino
IR
, Nogueira
EA
et al. Urodynamic effects of the combination of tamsulosin and daily tadalafil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, placebo-controlled clinical trial
. Int Urol Nephrol
. 2013
;45
(1
):39
–43
.20.
Sebastianelli
A
, Spatafora
P
, Frizzi
J
, Saleh
O
, Sessa
M
, De Nunzio
C
et al. Tadalafil 5 mg alone or in combination with tamsulosin 0.4 mg for the management of men with lower urinary tract symptoms and erectile dysfunction: results of a prospective observational trial
. J Clin Med
. 2019
;8
(8
):1126
.21.
Sharma
V
, Kumar
A
, Vasudevan
S
. Efficacy of tamsulosin and tadalafil combination therapy for lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) without erectile dysfunction (ED)
. Kerala Med J
. 2016
;9
(4
):156
–9
.22.
Singh
DV
, Mete
UK
, Mandal
AK
, Singh
SK
. A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs. tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia
. J Sex Med
. 2014
;11
(1
):187
–96
.23.
Wang
XH
, Shen
JW
. Clinical efficacy of tadalafil combined with tamsulosin in the treatment of male lower urinary tract symptoms
. Zhejiang Pract Med
. 2020
;25
(4
):258
–60
.24.
Wei
LJ
, Huang
KX
, Liu
H
, Li
XS
, Liu
ZW
, Qu
X
et al. Effect of low-dose tadalafil on lower urinary tract tymptoms with erectile
. Dysfunction
. 2020
;20
(52
):1
–3
.25.
Ye
XT
, Huang
H
, Huang
WP
, Zhang
FY
. Therapeutic effect of tadalafil on lower urinary tract symptoms with erectile dysfunction
. Zhonghua Nan Ke Xue
. 2019
;25
(6
):514
–21
.26.
Kallidonis
P
, Adamou
C
, Kotsiris
D
, Ntasiotis
P
, Verze
P
, Athanasopoulos
A
et al. Combination therapy with alpha-blocker and phosphodiesterase-5 inhibitor for improving lower urinary tract symptoms and erectile dysfunction in comparison with monotherapy: a systematic review and meta-analysis
. Eur Urol Focus
. 2020
;6
(3
):537
–58
.27.
Kloner
RA
. Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction
. Circulation
. 2004
;110
(19
):3149
–55
.28.
McVary
K
. Lower urinary tract symptoms and sexual dysfunction: epidemiology and pathophysiology
. BJU Int
. 2006
97
Suppl 2
23
8
; discussion 44–529.
Fusco
F
, D’Anzeo
G
, Sessa
A
, Pace
G
, Rossi
A
, Capece
M
et al. BPH/LUTS and ED: common pharmacological pathways for a common treatment
. J Sex Med
. 2013
;10
(10
):2382
–93
.30.
Angulo
J
, Cuevas
P
, Fernández
A
, La Fuente
JM
, Allona
A
, Moncada
I
et al. Tadalafil enhances the inhibitory effects of tamsulosin on neurogenic contractions of human prostate and bladder neck
. J Sex Med
. 2012
;9
(9
):2293
–306
.31.
Gacci
M
, Corona
G
, Salvi
M
, Vignozzi
L
, McVary
KT
, Kaplan
SA
et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia
. Eur Urol
. 2012
;61
(5
):994
–1003
.© 2023 S. Karger AG, Basel
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.
2023
You do not currently have access to this content.
