PDE5I in LUTS – how do they work – no proof yet
Reviewed by Gokul Vignesh Kanda Swamy

Phosphodiesterase type 5 (PDE5) inhibitors used in erectile dysfunction (ED) have been shown to improve lower urinary tract symptoms (LUTS) as well. The mechanism is not well understood. One of the hypotheses for benign prostatic hyperplasia (BPH) – LUTS is chronic ischaemia, and single dose tadalafil 20mg has shown to increase prostatic blood perfusion. The objective is to assess effects of 5mg once daily tadalafil (n=47) vs. placebo (n=50), for eight weeks, on prostatic blood flow measured by transrectal ultrasonography (TRUS) in men aged >45 years with moderate-to-severe BPH-LUTS. This was a multicentre, randomised, double-blind, parallel, placebo-controlled trial. Eligible criteria: diagnoses >six months ago, international symptom score (IPSS) >13, Qmax of >4 to <15ml/s (pre-void bladder volume of 150-550ml in ultrasound scan (USS) and voided volume >125ml). Men were excluded if they had saturation biopsy or conditions that could interfere with ultrasonographic blood flow measurement or reduce tolerance to transrectal ultrasound (TRUS). A standardised TRUS protocol was followed – patient position, urine volume in bladder, same probe and machine used for each patient, measurements taken in duplicate at bladder neck and at four sites in prostate in three transverse planes. Indices measured – resistance index (RI), pulsatility index (PI), acceleration time (AT), colour pixel intensity (CPI) and colour pixel density (CPD). The primary efficacy measure was the transition zone (TZ) RI. Secondary efficacy measures were RI in the peripheral zone and bladder neck, and CPI and CPD in all three regions. TRUS examinations were performed at baseline, four and eight weeks. The results showed no statistically significant change from baseline through to eight weeks in TZ RI, TZ CPI or CPD. The adverse event profile was consistent with previous studies. In conclusion, Tadalafil for eight weeks did not result in detectable decreases in arterial RI or increases in CPI or CPD in the prostate or bladder neck. It may be because of low baseline RI, insufficient sensitivity, or confounded by methodological variability across site or other mechanisms not assessed in this study. 

Effect of tadalafil once daily on prostate blood flow and perfusion in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, double-blind, multicenter, placebo-controlled trial.
Pinggera GM, Frauscher F, Paduch DA, et al.
UROLOGY
2014; Epub ahead of print.