Does It Matter How Tadalafil Improves Lower Urinary Tract Symptoms?

Abstract

The phosphodiesterase type 5 (PDE5) inhibitors have an established role in the treatment of erectile dysfunction (ED) [1]. Their mechanism of action involves potentiation of cyclic GMP,which is the active secondmessengermediating cavernosal smooth-muscle relaxation in the penis. For PDE5 inhibitors to be effective, there needs to be a neural stimulus, which means that the drugs have no effect at rest but become effective when the patient is sexually aroused. The target enzyme through which this effect is mediated is PDE5 within the cavernosal and arterial smooth muscle of the penis. Although the drugs can be taken regularly, their activity is essentially an on-demand response to a sexual stimulus. In recent years it has become clear that this class of drugs also provides benefit for men with lower urinary tract symptoms (LUTS). Although this does seem to be a class effect, only tadalafil is currently licensed for this indication, largely reflecting the pharmacokinetic properties of the drug that facilitate single daily dosing. Clinical trials demonstrate significant reductions in symptom scores, but urodynamic effects have been much less marked, with flow-rate changes usually not reaching statistical significance [2]. The current European Association of Urology guidelines state ‘‘PDE5 inhibitors reducemoderate to severe (storage and voiding) LUTS in men with or without erectile dysfunction’’ [2]. In contrast to the use of these drugs in ED, the mechanism of action of PDE5 inhibitors in male LUTS is much less clear, and has been the subject of several extensive reviews of the scientific and clinical data [3–5]. In short, it is assumed that the mechanism of action involves PDE5 inhibition rather than some other pharmacologic mechanism. There is evidence that PDE5 is present