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.

Ariana Smith

Ariana Smith

Ariana Smith

+ -1 Evaluators

Tadalafil, a phosphodiesterase type 5 (PDE-5) inhibitor, has been prescribed for daily use in the treatment of erectile dysfunction; a positive impact on lower urinary tract symptoms has been noted. This randomized, double-blind, placebo-controlled, multicenter trial compared tadalafil 20mg daily to placebo for the treatment of lower urinary tract symptoms secondary to prostatic hyperplasia. Noninvasive and invasive urodynamics, international prostate symptom score (IPSS) and adverse effects were assessed. The primary endpoint for this study was detrusor pressure at maximum urinary flow rate. Despite objective measures of bladder function being unchanged by tadalafil, significant subjective improvement in the IPSS was noted. Side effects were generally mild. While the mechanism of improvement in bladder symptoms cannot be elucidated from the data in this study, it does appear that this drug works differently from alpha-blockers. Alpha-blockers generally cause an increase in maximum flow rate, an effect not seen in this trial. Level-one evidence suggests that tadalafil can be offered for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Clinical judgment would suggest that this treatment would not be adequate or appropriate for men in retention or those with very high post-void residual urine volumes since no objective changes were seen in this study.

Alexander Roosen

Alexander Roosen

Alexander Roosen

+ -1 Evaluators

This is a commendable multicenter, randomized, double blind, placebo-controlled clinical trial comparing once-daily tadalafil 20mg vs. placebo during 12 weeks in men with lower urinary tract symptoms (LUTS) secondary to clinical benign prostatic hyperplasia (BPH) with or without bladder outlet obstruction. Detrusor pressure at maximum urinary flow rate (primary study endpoint) remained unchanged during the study with no statistically significant difference between tadalafil and placebo as were all other urodynamic parameters including maximum urinary flow rate, maximum detrusor pressure, bladder outlet obstruction index or bladder capacity. However, there was a significant improvement in international prostate symptom score (IPSS). It can be concluded that treatment with tadalafil for BPH-induced LUTS significantly improves symptoms but has no impact on objective voiding parameters. This study gives additional information for the use of phosphodiesterase type 5 (PDE-5) inhibitors in BPH/LUTS treatment.

Howard Goldman

Howard Goldman

Howard Goldman

+ -1 Evaluators

Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, has been shown in prior studies to cause symptomatic improvement in lower urinary tract symptoms (LUTS) in men as measured by the International Prostate Symptom Score (IPSS). The mechanism by which this occurs is not fully understood, but it is thought to involve relaxation of the bladder smooth muscle. There are few data to evaluate whether there are urodynamic changes occurring as, potentially, bladder muscle relaxation in the setting of obstruction could lead to untoward effects. This study compared urodynamic findings in men with LUTS related to benign prostatic hyperplasia (BPH) with or without obstruction given 20mg tadalafil daily versus those who received placebo. There were no significant urodynamic changes noted. When appropriate, it appears reasonable to use tadalafil, a PDE5 inhibitor, to ameliorate LUTS without worrying that is will impact the patient's ability to void.

Francisco Cruz

Francisco Cruz

Francisco Cruz

+ -1 Evaluators

Tadalafil once a day is now one option for the treatment of male lower urinary tract symptoms (LUTS). Interestingly, systematic improvement of LUTS has been observed by the several randomised controlled trials (RCTs) that have so far compared tadalafil (and other phosphodiesterase 5 inhibitors [PDE5-i]) in men with LUTS attributed to benign prostatic hyperplasia (BPH). That was confirmed by a recent meta-analysis {1}. Surprisingly, such increment was not associated with an improvement in urinary free flow. This RCT explores the possibility of tadalafil causing an unrecognized impairment of detrusor contractility. The study randomised 99 patients to tadalafil 20mg and 101 patients to placebo. Data were available for 83 and 89 patients, respectively. No statistically significant difference between tadalafil and placebo was observed in detrusor pressure at maximum urinary flow rate (primary outcome) or any other urodynamic parameter assessed including maximum urinary flow rate, maximum detrusor pressure, bladder outlet obstruction index or bladder capacity. As in previous studies, a large difference in the final American Urological Association (AUA) score (-4.2 points) was observed between tadalafil and placebo. In conclusion, there is no evidence that continuous administration of tadalafil 20mg for 12 weeks causes any deleterious effect of bladder contractility.

Andreas Skolarikos

Andreas Skolarikos

Andreas Skolarikos

Grigoris Athanasiadis

Grigoris Athanasiadis

Grigoris Athanasiadis

+ 0 Evaluators

We have chosen this article because it investigates an area of increasing interest regarding the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH LUTS). Interestingly, although tadalafil and other phosphodiesterase 5 (PDE5) inhibitors seem to significantly improve BPH LUTS compared to placebo in various studies, as demonstrated through International Prostate Symptom Score (IPSS) assessment, these findings have not been demonstrated through statistically significant Qmax improvement either. This study explores invasive and non-invasive urodynamic parameters, IPSS and safety, comparing tadalafil 20mg once daily versus placebo for 12 weeks in 172 men with BPH LUTS with or without bladder outlet obstruction. No significant difference was noted between tadalafil and placebo in any of the urodynamic measures investigated, leading to the conclusion that there is no suggestion of negative impact on bladder function. Once more, significant improvement in IPSS was noted (p<0.001) with an overall relatively safe profile. A few significant limitations of the study, though, should be taken into account, such as the fairly large number of patients included without bladder outlet obstruction and the tadalafil dose chosen, which can definitely call for discussion. Obviously, thorough investigation of the exact mechanism of action through which PDE5 inhibitors impact BPH LUTS becomes necessary.

Ryuji Sakakibara

Ryuji Sakakibara

Ryuji Sakakibara

+ -1 Evaluators

NOergic pathways affect prostate and lower urinary tract function. Although urodynamic changes were minimal in this noteworthy study, NOergic pathways are worth investigating since they are beneficial for vascular supply as well.