The Role of 5-Phosphodiesterase Inhibitors (PDE-5I) in Current Benign Prostatic Hyperplasia Treatment: A Narrative Review

Abstract

Introduction: 5-phosphodiesterase inhibitors (PDE-5I) have been investigated as a treatment for urinary dysfunction for almost a decade. The general perception is that they play a significant role in managing lower urinary tract symptoms (LUTS), particularly those associated with benign prostatic hyperplasia (BPH). However, the specific biochemical processes by which PDE-5I repairs urinary function are still poorly understood and there is little instrumental evidence of significant improvement in urinary symptoms. Therefore, we explore the role of 5-phosphodiesterase inhibitors (PDE-5I) as complementary to the conventional treatment of symptomatic BPH; we provide the suggested biological procedures involved in the association between PDE-5 inhibitor use and improvement in LUTS; and we propose new approaches to this topic. Material and Methods: A systematic search for clinical trials, experimental studies, and systematic reviews was performed in electronic libraries (PubMed, EMBASE, Scopus) using the terms "benign prostate hypertrophy", "benign prostate hyperplasia", "lower urinary tract symptoms", "storage symptoms", "voiding symptoms", "bladder outlet obstruction" and the keywords "mechanism of action", "synergy", "PDE-5 inhibitor", "alpha1-adrenergic antagonist", "5-alpha-reductase inhibitors" in various combinations. There was no restriction on publication date. Results: To date, only a few randomized studies have been published in which the effect of the combination of a conventional drug for the treatment of symptomatic BPH and a PDE-5I was investigated. Almost all showed significant improvement in IPSS and QoL. Some studies showed significant improvements in maximum urine flow (Qmax) and postvoiding residual volume (PVR) with combination therapy compared with a single agent alone. Conclusions: PDE-5I seems effective in relieving symptoms of some BPH patients when administered as complementary to agents currently used to treat BPH. However, the mechanism of action of PDE-5 inhibitors in LUTS remains poorly understood and it is difficult to determine the specific subset of BPH patients who will benefit from the combination of PDE-5 inhibitors with the current treatment. Well-designed, sufficiently informative comparative studies focusing on specific target group profiles (age, urogenital parameters) are needed to define new therapeutic options.

Keywords: 5-alpha-reductase inhibitors; PDE-5 inhibitor; alpha1-adrenergic antagonist; benign prostate hypertrophy; bladder outlet obstruction; lower urinary tract symptoms.

Figure 1

Pooled summary of 4 randomized controlled trials included in this review, comparing the effect of therapy of BPH patients with a combination of alpha1-adrenoceptor antagonists (AB) and 5-phosphodiesterase inhibitors (PDE-5I) vs. AB plus placebo. Forest plots indicate the mean difference of pre-post treatment improvements of (i) IPSS total scores, (ii) peak urinary flow (Qmax) and (iii) post-void residual volume (PVR). Data to the right of the vertical no-effect line of forest plots represent a favorable effect of combination therapy versus single-agent plus placebo. Diamonds represent overall effect sizes extending to the limits of the 95% confidence intervals of mean differences. The significance of the pooled effect sizes (Z statistics) and heterogeneity data (I², Chi-square, p value) are shown. Inverse variance statistics, random effects model. RevMan 5.3. When not disclosed in study reports, standard deviations were calculated using the imputeSD package on the R platform. Bechara 2008 is [9], Gacci 2012 is [10], Regadas 2013 is [11], Tuncel 2010 is [12].