Phosphodiesterase type-5 inhibitors for lower urinary tract symptoms: A story to tell or not?

No fully accepted mechanism of action has been accepted to explain the unusual dossier that PDE-5 inhibitors exhibit in male LUTS.

A recent abstract by Roehrborn et al further supports the notion that PDE-5 inhibitors and specifically tadalafil (Cialis) improve both LUTS and erectile function (see "Phosphodiesterase type-5 inhibitor improves both erectile dysfunction, benign prostatic hyperplasia symptoms"). The randomized study found that both the 2.5-mg and 5-mg dose of tadalafil improved the International Index of Erectile Function erectile function domain versus placebo; only the 5-mg dose improved International Prostate Symptom Score (–6.1 vs. –3.8 for placebo).

What has been troubling about the PDE-5 story is that, frankly, there is no story. No fully accepted mechanism of action has been accepted to explain the unusual dossier that these drugs exhibit in male LUTS. Do they work on the bladder? Given that obstructive (voiding) symptoms improve with these agents as opposed to antimuscarinic agents, which only alleviate storage symptoms, that is unlikely. Do they work on the prostate? If so, then why doesn't flow rate increase and/or detrusor pressure at maximum flow decrease?

Finally, we know that improvement in sexual function improves LUTS and vice versa. Although the study authors report that baseline sexual function does not predict improvement in urinary symptom scores, it is based on a categorical evaluation of erectile function; ie, a yes or no answer to having a history of ED. One can imagine that if the manufacturers of PDE-5 inhibitors had gone to the FDA for drug approval and their datasets were based solely on a yes or no answer on the presence of ED, approval of these drugs would not have been granted.

Until a clearly delineated mechanism of action explaining the unusual clinical profile of tadalafil is established, its role in male LUTS will be questioned.

Dr. Kaplan, a member of the Urology Times Editorial Council, is professor of urology at Weill Cornell Medical College, New York.