Skip to main content
Top
Published in: World Journal of Urology 1/2019

01-01-2019 | Original Article

Alpha-blockers with or without phosphodiesterase type 5 inhibitor for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis

Authors: Jianzhong Zhang, Xiao Li, Bin Yang, Cheng Wu, Yanghua Fan, Hongjun Li

Published in: World Journal of Urology | Issue 1/2019

Login to get access

Abstract

Purpose

Recently, several randomized controlled trials (RCTs) explored the effects of α-blockers with or without phosphodiesterase type 5 inhibitors (PDE5-Is) for lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). However, the results were inconsistent. We performed this meta-analysis to evaluate the role of combination therapy (α-blockers and PDE5-Is) in patients with LUTS/BPH.

Materials and methods

Databases including PubMed, Cochrane library, Web of Science, and Embase were searched for qualified RCTs. Pooled mean differences (MDs) and odds ratios (ORs) were calculated to measure the effects and adverse events in combination therapy. Moreover, subgroup analyses of ethnicity, dosage of PDE5-Is, treatment duration, and severity of LUTS/BPH were performed. In addition, trial sequential analyses (TSAs) were used to assess whether the evidence for the results was sufficient.

Results

Overall, this study identified 11 eligible RCTs, including 855 LUTS/BPH patients. Patients receiving combination therapy had better improvement in international prostate symptom score (IPSS: MD: 1.66, 95% CI − 3.03 to − 0.29), maximum urinary flow rate (Qmax: MD: 0.94, 95% CI 0.24–1.64), and international index of erectile function (IIEF: MD: 4.73, 95% CI 2.95–6.51), comparing those without PDE5-Is. Besides, subgroup analyses indicated that the effects of combination treatment were associated with ethnicity, treatment duration, and severity of LUTS/BPH. By TSA, the findings in the current study were based on sufficient evidence.

Conclusions

Our results indicated that combination therapy can significantly improve IPSS, Qmax, and IIEF in patients with LUTS/BPH. Combination therapy might be more suitable for these patients.

Literature
  1. Gratzke C, Bachmann A, Descazeaud A, Drake MJ, Madersbacher S, Mamoulakis C, Oelke M, Tikkinen KAO, Gravas S (2015) EAU guidelines on the assessment of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 67:1099–1109. https://​doi.​org/​10.​1016/​j.​eururo.​2014.​12.​038 View ArticlePubMed
  2. Martin SA, Haren MT, Marshall VR, Lange K, Wittert GA (2011) Prevalence and factors associated with uncomplicated storage and voiding lower urinary tract symptoms in community-dwelling Australian men. World J Urol 29:179–184. https://​doi.​org/​10.​1007/​s00345-010-0605-8 View ArticlePubMed
  3. Alawamlh OAH, Goueli R, Lee RK (2018) Lower urinary tract symptoms, benign prostatic hyperplasia, and urinary retention. Med Clin N Am 102:301–311. https://​doi.​org/​10.​1016/​j.​mcna.​2017.​10.​005 View ArticlePubMed
  4. Ficarra V, Rossanese M, Zazzara M, Giannarini G, Abbinante M, Bartoletti R, Mirone V, Scaglione F (2014) The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. Curr Urol Rep. 15:463. https://​doi.​org/​10.​1007/​s11934-014-0463-9 View ArticlePubMed
  5. Yuan JQ, Mao C, Wong SY, Yang ZY, Fu XH, Dai XY, Tang JL (2015) Comparative effectiveness and safety of monodrug therapies for lower urinary tract symptoms associated with benign prostatic hyperplasia: a network meta-analysis. Medicine (Baltimore). 94:e974. https://​doi.​org/​10.​1097/​md.​0000000000000974​ View ArticlePubMedPubMed Central
  6. Gacci M, Sebastianelli A, Spatafora P, Corona G, Serni S, De Ridder D, Gravas S, Abrams P (2018) Best practice in the management of storage symptoms in male lower urinary tract symptoms: a review of the evidence base. Ther Adv Urol. 10:79–92. https://​doi.​org/​10.​1177/​1756287217742837​ View ArticlePubMed
  7. MacDonald R, Brasure M, Dahm P, Olson CM, Nelson VA, Fink HA, Risk MC, Rwabasonga B, Wilt TJ (2018) Efficacy of newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a systematic review. Aging Male. https://​doi.​org/​10.​1080/​13685538.​2018.​1434503 View ArticlePubMed
  8. Thomas D, Chughtai B, Kini M, Te A (2017) Emerging drugs for the treatment of benign prostatic hyperplasia. Expert Opin Emerg Drugs. 22:201–212. https://​doi.​org/​10.​1080/​14728214.​2017.​1369953 View ArticlePubMed
  9. Djavan B, Chapple C, Milani S, Marberger M (2004) State of the art on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Urology. 64:1081–1088. https://​doi.​org/​10.​1016/​j.​urology.​2004.​07.​031 View ArticlePubMed
  10. van Dijk MM, de la Rosette JJ, Michel MC (2006) Effects of alpha(1)-adrenoceptor antagonists on male sexual function. Drugs 66:287–301View ArticlePubMed
  11. Giuliano F, Uckert S, Maggi M, Birder L, Kissel J, Viktrup L (2013) The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol 63:506–516. https://​doi.​org/​10.​1016/​j.​eururo.​2012.​09.​006 View ArticlePubMed
  12. Taoka R, Kakehi Y (2017) The influence of asymptomatic inflammatory prostatitis on the onset and progression of lower urinary tract symptoms in men with histologic benign prostatic hyperplasia. Asian J Urol. 4:158–163. https://​doi.​org/​10.​1016/​j.​ajur.​2017.​02.​004 View ArticlePubMedPubMed Central
  13. Morelli A, Sarchielli E, Comeglio P, Filippi S, Mancina R, Gacci M, Vignozzi L, Carini M, Vannelli GB, Maggi M (2011) Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. J Sex Med. 8:2746–2760. https://​doi.​org/​10.​1111/​j.​1743-6109.​2011.​02416.​x View ArticlePubMed
  14. Wang XH, Wang X, Shi MJ, Li S, Liu T, Zhang XH (2015) Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and alpha-adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH. Asian J Androl. 17:1022–1032. https://​doi.​org/​10.​4103/​1008-682x.​154990 View ArticlePubMedPubMed Central
  15. Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, Roehrborn CG, Serni S, Mirone V, Carini M, Maggi M (2012) A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 61:994–1003. https://​doi.​org/​10.​1016/​j.​eururo.​2012.​02.​033 View ArticlePubMed
  16. Oelke M, Shinghal R, Sontag A, Baygani SK, Donatucci CF (2015) Time to onset of clinically meaningful improvement with tadalafil 5 mg once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: analysis of data pooled from 4 pivotal, double-blind, placebo controlled studies. J Urol 193:1581–1589. https://​doi.​org/​10.​1016/​j.​juro.​2014.​11.​094 View ArticlePubMed
  17. Takeda M, Yokoyama O, Yoshida M, Nishizawa O, Hirata K, Nakaoka R, Takita Y, Murakami M (2017) Safety and efficacy of the combination of once-daily tadalafil and alpha-1 blocker in Japanese men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a randomized, placebo-controlled, cross-over study. Int J Urol 24:539–547. https://​doi.​org/​10.​1111/​iju.​13357 View ArticlePubMed
  18. Karami H, Hassanzadeh-Hadad A, Fallah-Karkan M (2016) Comparing monotherapy with tadalafil or tamsulosin and their combination therapy in men with benign prostatic hyperplasia: a randomized clinical trial. Urol J. 13:2920–2926PubMed
  19. Fawzi A, Kamel M, Salem E, Desoky E, Omran M, Elgalaly H, Sakr A, Maarouf A, Khalil S (2017) Sildenafil citrate in combination with tamsulosin versus tamsulosin monotherapy for management of male lower urinary tract symptoms due to benign prostatic hyperplasia: a randomised, double-blind, placebo-controlled trial. Arab J Urol. 15:53–59. https://​doi.​org/​10.​1016/​j.​aju.​2016.​11.​001 View ArticlePubMed
  20. Kumar S, Kondareddy C, Ganesamoni R, Nanjappa B, Singh SK (2014) Randomized Controlled trial to assess the efficacy of the combination therapy of alfuzosin and tadalafil in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. Low Urin Tract Symptoms. 6:35–40. https://​doi.​org/​10.​1111/​luts.​12016 View ArticlePubMed
  21. Regadas RP, Reges R, Cerqueira JB, Sucupira DG, Josino IR, Nogueira EA, Jamacaru FV, de Moraes MO, Silva LF (2013) 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 45:39–43. https://​doi.​org/​10.​1007/​s11255-012-0317-7 View ArticlePubMed
  22. Abolyosr A, Elsagheer GA, Abdel-Kader MS, Hassan AM, Abou-Zeid AM (2013) Evaluation of the effect of sildenafil and/or doxazosin on Benign prostatic hyperplasia-related lower urinary tract symptoms and erectile dysfunction. Urol Ann. 5:237–240. https://​doi.​org/​10.​4103/​0974-7796.​120293 View ArticlePubMedPubMed Central
  23. Gacci M, Vittori G, Tosi N, Siena G, Rossetti MA, Lapini A, Vignozzi L, Serni S, Maggi M, Carini M (2012) A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med. 9:1624–1633. https://​doi.​org/​10.​1111/​j.​1743-6109.​2012.​02718.​x View ArticlePubMed
  24. Ozturk MI, Kalkan S, Koca O, Gunes M, Akyuz M, Karaman MI (2012) Efficacy of alfuzosin and sildenafil combination in male patients with lower urinary tract symptoms. Andrologia. 44(Suppl 1):791–795. https://​doi.​org/​10.​1111/​j.​1439-0272.​2011.​01268.​x View ArticlePubMed
  25. Tuncel A, Nalcacioglu V, Ener K, Aslan Y, Aydin O, Atan A (2010) Sildenafil citrate and tamsulosin combination is not superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. World J Urol 28:17–22. https://​doi.​org/​10.​1007/​s00345-009-0484-z View ArticlePubMed
  26. Bechara A, Romano S, Casabe A, Haime S, Dedola P, Hernandez C, Rey H (2008) Comparative efficacy assessment of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study. J Sex Med. 5:2170–2178. https://​doi.​org/​10.​1111/​j.​1743-6109.​2008.​00940.​x View ArticlePubMed
  27. Kaplan SA, Gonzalez RR, Te AE (2007) Combination of alfuzosin and sildenafil is superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. Eur Urol 51:1717–1723. https://​doi.​org/​10.​1016/​j.​eururo.​2007.​01.​033 View ArticlePubMed
  28. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269, W64
  29. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 340:c869. https://​doi.​org/​10.​1136/​bmj.​c869 View ArticlePubMedPubMed Central
  30. Zhang J, Yang B, Xiao W, Li X, Li H (2018) Effects of testosterone supplement treatment in hypogonadal adult males with T2DM: a meta-analysis and systematic review. World J Urol. https://​doi.​org/​10.​1007/​s00345-018-2256-0 View ArticlePubMedPubMed Central
  31. Li X, Shen M, Cai H, Liu K, Liu Y, Huang Z, Liang C, Deng X, Ye J, Zou Q, Li J (2016) Association between manganese superoxide dismutase (MnSOD) polymorphism and prostate cancer susceptibility: a meta-analysis. Int J Biol Markers 31:e422–e430. https://​doi.​org/​10.​5301/​jbm.​5000188 View ArticlePubMed
  32. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, Gluud LL, Als-Nielsen B, Gluud C (2009) Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses? Int J Epidemiol 38:276–286. https://​doi.​org/​10.​1093/​ije/​dyn179 View Article
  33. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://​doi.​org/​10.​1136/​bmj.​327.​7414.​557 View ArticlePubMedPubMed Central
  34. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials. 7:177–188View ArticlePubMed
  35. DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 28:105–114. https://​doi.​org/​10.​1016/​j.​cct.​2006.​04.​004 View Article
  36. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ. 315:629–634View ArticlePubMedPubMed Central
  37. Uckert S, Kuthe A, Jonas U, Stief CG (2001) Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol. 166:2484–2490View ArticlePubMed
  38. Francis SH, Busch JL, Corbin JD, Sibley D (2010) cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 62:525–563. https://​doi.​org/​10.​1124/​pr.​110.​002907 View ArticlePubMedPubMed Central
  39. Yokoyama O, Igawa Y, Takeda M, Yamaguchi T, Murakami M, Viktrup L (2015) Tadalafil for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a review of clinical data in Asian men and an update on the mechanism of action. Ther Adv Urol. 7:249–264. https://​doi.​org/​10.​1177/​1756287215589238​ View ArticlePubMedPubMed Central
  40. Kolontarev K, Govorov A, Kasyan G, Priymak D, Pushkar D (2016) Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors. Cent Eur J Urol 69:398–403. https://​doi.​org/​10.​5173/​ceju.​2016.​879 View Article
  41. Shim SR, Kim JH, Chang IH, Shin IS, Hwang SD, Kim KH, Yoon SJ, Song YS (2016) Is tamsulosin 0.2 mg effective and safe as a first-line treatment compared with other alpha blockers? A meta-analysis and a moderator focused study. Yonsei Med J 57:407–418. https://​doi.​org/​10.​3349/​ymj.​2016.​57.​2.​407 View ArticlePubMedPubMed Central
Metadata
Title
Alpha-blockers with or without phosphodiesterase type 5 inhibitor for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis
Authors
Jianzhong Zhang
Xiao Li
Bin Yang
Cheng Wu
Yanghua Fan
Hongjun Li
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 1/2019
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-018-2370-z

Other articles of this Issue 1/2019

World Journal of Urology 1/2019 Go to the issue