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
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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.
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.
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.
KeywordsLower urinary tract symptom Benign prostatic hyperplasia Phosphodiesterase type 5 inhibitor α-Blocker
This work is supported by the grant from the National Natural Science Foundation of China (81671488) and the Beijing Natural Science Foundation (Grant No. 7162152).
HJL: project development and manuscript writing. JZZ: data collection and manuscript writing. XL: data collection and data analysis. BY: data collection and data analysis. CW: data collection. YHF.: data analysis.
This study was funded by the National Natural Science Foundation of China (81671488) and the Beijing Natural Science Foundation (Grant no. 7162152).
Compliance with ethical standards
Conflict of interest
Hongjun Li has received research grants from the National Natural Science Foundation of China (81671488) and the Beijing Natural Science Foundation (Grant no. 7162152).
Informed consent was obtained from all individual participants included in the study.
Research involving human participants and/or animals
For this type of study formal consent is not required. This article does not contain any studies with animals performed by any of the authors.
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 PubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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, W64Google Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar