Phosphodiesterase-5 Inhibitors: Are the Panacea for Several Urologic Diseases?

The urologic literature has never been consumed by the tumult as recently happened for medical expulsive therapy.

According to the meta-analysis published by Bai et al., ¹ tadalafil alone or in combination with tamsulosin for the treatment of distal ureteral stones seems to be effective and safe.

The background behind this concept comes from the identification of nitrergic fibers in the distal ureter and the potential relaxant effects of phosphodiesterase-5 inhibitors on ureteral smooth muscle.

This issue is particularly intriguing especially at this moment in time in which two large randomized double-blind placebo-controlled studies did not show any clinical benefit in favor of tamsulosin for promoting ureteral stone passage. ^2,3

However, the key message postulated by the authors about the adjuvant use of tadalafil should be considered with caution.

As a matter of fact, although well conducted, this meta-analysis lacks several randomized, large sample size, double-blind, placebo-controlled studies to corroborate the validity of the conclusion.

In addition, all the studies used a dosage of 10 mg of taladafil daily that may generate an important concern: is this high dosage correct and safe? In other words, is there a non-negligible risk that pros might be outweighed by cons of this drug with this unusual high dosage?

Furthermore, adverse events, even though mild and well tolerated, should not be underestimated in terms of frequency. As such, in the future, the effectiveness and safety of lower dose of tadalfil on ureteral stone expulsion should also be evaluated.

Moreover, as the authors said, one common bias of all the studies included in the meta-analysis is the lack of information about the frequency of sexual intercourses of the study population that could be an additional supplement of nitric oxide release for ureteral relaxation and consequently stone expulsion in other words neglecting the role of “vis medicatrix naturae” that, as reported in the ancient time by Hippocrates, often helps doctors inadvertently.

The data reported should be incontrovertibly reliable because they might also imply an off-label extensive utilization of this costly drug worldwide that, for instance, is not reimbursed by public health system in many countries.

Consequently, before loading the population of a significant extra cost, evidence of its effectiveness should be robust and clear.

Having said this, is tadalafil really becoming a sort of panacea for several urologic diseases?

To conclude, I would borrow a sentence from a famous Italian poet Alessandro Manzoni: “Is this true glory? Judgement waits posterity.”