The use of PDE-5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia
- 447 Downloads
The relationship between lower urinary tract symptoms secondary to BPH and ED has recently been the subject of significant research due to the prevalence of both conditions concomitantly existing in older men. Many large-scale studies have demonstrated an association between erectile dysfunction and lower urinary tract symptoms. Although the mechanisms underlying the relationship between LUTS and ED are not fully elucidated, several theories are currently proposed in literature: the nitric oxide/cGMP pathway, RhoA/Rho-kinase signaling, pelvic atherosclerosis associated with chronic hypoxia, and autonomic adrenergic hyperactivity. The mechanisms by which these pathways affect the bladder, prostate, pelvic vasculature and spinal cord are also the subject of current research. In this chapter, we examine the randomized, placebo-controlled trials that have evaluated the use of PDE-5Is in LUTS, as well as randomized, controlled trials (RCTs) researching combination PDE-5Is and alpha blockers.
KeywordsPDE-5 INHIBITORS Benign Prostatic Hyperplasia AUA Symptom Index (AUA-SI) Lower Urinary Tract Symptoms (LUTS)
Compliance with Ethics Guidelines
Conflict of Interest
Dr. Casey Lythgoe reported no potential conflicts of interest relevant to this article.
Dr. Kevin McVary received consultancies and honoraria from Allergan, Lilly/ICOS, NxThera, and Watson Pharmaceuticals. Dr. McVary received honoraria and payment for the development of educational presentations including service on speakers’ bureaus from GSK.
Dr. McVary serves as a Section Editor for Current Urology Reports.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of outstanding importance
- 5.•• Wein AJ, Coyne KS, Tubaro A, et al. The impact of lower urinary tract symptoms on male sexual health: EpiLUTS. BJU Int. 2009;103 Suppl 3:33–41. doi: 10.1111/j.1464-410X.2009.08447.x.19. The EpiLUTS study was one of the first large-scale studies to demonstrate the relationship between LUTS and ED..PubMedCrossRefGoogle Scholar
- 8.Podlasek CA, Bond CW, McVary KT, et al. Analysis of Changes in Nitric Oxide Synthase Signaling in BB/WOR Diabetic Prostate. Androl. Feb 15, 2012.Google Scholar
- 9.Richter K, Heuer O, Uckert S, Stief CG, Jonas U, Wolf G. Immunocytochemical distribution of nitric oxide synthases in the human prostate [Abstract 347]. J Urol. 2004;171(Suppl):262–6.Google Scholar
- 14.Sandra Filippi, Annamaria Morelli, Peter Sandner, Benedetta Fibbi, Rosa Mancina, Mirca Marini, Mauro Gacci, Linda Vignozzi, Gabriella Barbara Vannelli, Marco Carini, Gianni Forti, and Mario Maggi Characterization and Functional Role of Androgen-Dependent PDE5 Activity in the Bladder Endocrinology. 2007;148(3):1019–29.Google Scholar
- 32.Morelli A, Sarchielli E, Comeglio P, Filippi S, Mancina R, Gacci M, et al. 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. 2011;8(10):2746–60.PubMedCrossRefGoogle Scholar
- 33.Füllhase C, Hennenberg M, Giese A, Schmidt M, Strittmatter F, Soler R, Gratzke C, Andersson KE, Stief C. Presence of phosphodiesterase type 5 (PDE5) in the spinal cord and its involvement in bladder outflow obstruction related bladder overactivity. J Urol. 2013 Mar 29. doi: 10.1016/j.juro.2013.03.112.
- 36.• Kevin T. McVary,William Monnig, Joseph L. Camps, Jr., Jay M. Young, Li-Jung Tseng and Gene van den Ende Sildenafil Citrate Improves Erectile Function and Urinary Symptoms in Men With Erectile Dysfunction and Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Randomized, Double-Blind Trial. Journal of Urology March. 2007;177:1071–1077. Randomized placebo-controlled study investigating the effect of Sildenafil on LUTS. Google Scholar
- 37.•• McVary KT, Roehrborn CG, Kaminetsky JC, Auerbach SM, Wachs B, Young JM, et al. Tadalafil Relieves Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. J Urol. 2007;177:1401–7. Randomized placebo-controlled study investigating the effect of Tadalafil on LUTS using dose escalation..PubMedCrossRefGoogle Scholar
- 38.• Stief CG, Porst H, Neuser D, Beneke M, Ulbrich E. A Randomised, Placebo-Controlled Study to Assess the Efficacy of Twice Daily Vardenafil in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. Eur Urol. 2008;53:1236–44. Randomized placebo-controlled study investigating the effect of Vardenafil on LUTS.PubMedCrossRefGoogle Scholar
- 39.• Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil Administered Once Daily for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Dose Finding Study. J Urol. 2008;180:1228–34. Randomized placebo-controlled study investigating the effect of Tadalafil on LUTS, which also examines differences in dosing.PubMedCrossRefGoogle Scholar
- 40.• Porst H, McVary KT, Montorsi F, Sutherland P, Elion-Mboussa A, Wolka AM, et al. Effects of Once-Daily Tadalafil on Erectile Function in Men with Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia. Eur Urol. 2009;56. Randomized placebo-controlled study investigating the effect of Tadalafil on LUTS.Google Scholar
- 41.• Nihad AM, Tamimi, Ivan Mincik, Scott Haughie, Janice Lamb, Anna Crossland and Peter Ellis A placebo-controlled study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia. BJU Int 2010. Randomized placebo-controlled study investigating the effect of UK-369,003 on LUTS.Google Scholar
- 42.• Hartmut Porst, Edward D. Kim, Adolfo R. Casabé, Vincenzo Mirone, Roberta J. Secrest, Lei Xu, David P. Sundin, Lars Viktrup, for the LVHJ study team Efficacy and Safety of Tadalafil Once Daily in the Treatment of Men With Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Results of an International Randomized, Double-Blind, Placebo-Controlled Trial. Eur Urol 2011. Randomized placebo-controlled study investigating the effect of Tadalafil on LUTS. Google Scholar
- 43.Dmochowski R, Roehrborn C, Klise S, Xu L, Kaminetsky J, Kraus S. Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial. J Urol. 2010;183(3):1092–7.PubMedCrossRefGoogle Scholar
- 44.•• 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. Comprehensive meta-analysis of the use of PDE5Is for LUTS, including randomized placebo-controlled trials as well as trials comparing combination therapy with alpha-blockers.PubMedCrossRefGoogle Scholar