PDE5 inhibitors reduce urinary tract symptoms in men with enlarged prostate

Last Updated: 2016-02-04

By Will Boggs MD

NEW YORK (Reuters Health) - Phosphodiesterase type 5 inhibitors (PDE5-Is) reduce lower urinary tract symptoms (LUTS) in men with prostate enlargement with or without erectile dysfunction (ED), according to a systematic review.

"PDE5-Is, and in particular tadalafil, are effective in improving LUTS and erectile function compared with placebo," Dr. Mauro Gacci from University of Florence in Italy told Reuters Health by email. "There is no first-choice drug: all treatments must be tailored for each patient."

Both LUTS and ED are amenable to therapy with PDE5-Is, though the mechanisms behind these improvements remain unclear.

Dr. Gacci and colleagues reviewed the current knowledge on the potential mechanisms of action of PDE5-Is on LUTS/benign prostatic enlargement (BPE) and analyzed relevant data from the current literature on the clinical use of PDE5-Is (especially once-daily tadalafil) for the treatment of LUTS/BPE.

In their January 22 European Urology online report, they say various studies support five possible rationales for using PDE5-Is in men with LUTS/BPE: (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.

Systematic reviews and meta-analyses demonstrated significant improvements in urinary symptoms and erectile function, despite a negligible improvement in maximum urinary flow rates, they note.

Moreover, the combination of PDE5-Is and alpha1-blockers improved urinary symptoms, erectile function, and urinary flow rates compared with the use of alpha1-blockers alone.

A subset analysis of tadalafil studies showed remarkable improvements in LUTS/BPE in men with BPE alone and in those with comorbid ED and BPE, the authors said.

The main reported side effects associated with tadalafil and other PDE5-I use include dyspepsia, back pain, gastroesophageal reflux, and headache.

Dr. Gacci added, "Post-hoc analyses on tadalafil indicate that tadalafil: 1) allows to achieve a clinically meaningful improvement of urinary symptoms; 2) has an effect on nocturia; 3) the activity on urinary symptoms is independent from erectile function/erectile dysfunction and 4) no baseline characteristics are able to predict a favorable or unfavorable clinical outcome (it works in every patient)."

Dr. Germar-Michael Pinggera from Medical University of Innsbruck Austria worked on one of the trials that showed beneficial effects of once-daily tadalafil in men with LUTS/BPE (http://bit.ly/1P9sG2H).

He told Reuters Health by email, "Tadalafil even in the lowest dosage of 5 mg once a day seems in several comparable studies at least equally effective in improvement of urinary flow rate compared to alpha blockers. Albeit both different types of drugs are characterized by only a very small increase in urinary flow rate, they distinguish themselves by a high subjective satisfaction rate measured by different validated symptom scores."

"Whereas the highly prescribed alpha-blockers might exhibit negative effects on several sexual items like ejaculation or orgasmic frequency, tadalafil itself stands out due to simultaneous improvement in such items as well as improved LUTS symptoms," Dr. Pinggera said. "Amazing is the unanimity of results of several studies, including randomized controlled trials."

The study had no external funding. Six coauthors reported disclosures.

SOURCE: http://bit.ly/1PX5zMk

Eur Urol 2016.