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 Jul;70(1):124-133. doi: 10.1016/j.eururo.2015.12.048. Epub 2016 Jan 22.


Context: Several preclinical reports, randomized controlled trials, systematic reviews, and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of men with lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE).

Objective: Update of the latest evidence on the mechanisms of action, evaluate the current meta-analyses, and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE.

Evidence acquisition: Literature analysis of basic researches on PDE5-Is, systematic literature search in PubMed and Scopus until May 2015 on reviews of trials on PDE5-Is, and collection of pooled data available on tadalafil 5mg.

Evidence synthesis: Latest evidences on the pathophysiology of LUTS/BPE has provided the rationale for use of PDE5-Is: (1) improvement of LUT oxygenation, (2) smooth muscle relaxation, (3) negative regulation of proliferation and transdifferentiation of LUT stroma, (4) reduction of bladder afferent nerve activity, and (5) down-regulation of prostate inflammation are the proven mechanisms of action of PDE5-Is. Data from eight systematic reviews demonstrated that PDE5-Is allow to improve LUTS (International Prostate Symptom Score mean difference vs placebo: 2.35-4.21) and erectile function (International Index of Erectile Function mean difference vs placebo: 2.25-5.66), with negligible change in flow rate (Qmax mean difference vs placebo: 0.01-1.43). Pooled data analyses revealed that tadalafil 5mg once daily allows the clinically-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement.

Conclusions: PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE. Data on the reduction of disease progression, long-term outcomes, and cost-effectiveness analyses are still lacking.

Patient summary: We reviewed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement. We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction.

Keywords: Avanafil; Benign prostatic enlargement; Benign prostatic hyperplasia; Erectile dysfunction; Lower urinary tract symptoms; Phosphodiesterase type 5 inhibitors; Prostate; Sildenafil; Tadalafil; Vardenafil.

Publication types

  • Review

MeSH terms

  • Afferent Pathways / drug effects
  • Animals
  • Cell Proliferation / drug effects
  • Cell Transdifferentiation / drug effects
  • Erectile Dysfunction / drug therapy
  • Humans
  • Male
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects
  • Penile Erection / drug effects
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Prostatism / drug therapy*
  • Prostatitis / drug therapy
  • Urinary Bladder / innervation
  • Urinary Tract Physiological Phenomena / drug effects


  • Phosphodiesterase 5 Inhibitors