Effect of tadalafil in improving bph/luts: preliminary results of a randomized double-blind placebo-controlled clinical trial

To evaluate the effect of in vivo treatment with tadalafil 5mg daily on a population of adult men complaining LUTS/BPH waitlisted for simple prostatectomy in improving clinical and molecular outcomes of prostatic inflammation. 86 subjects on the waiting list for simple prostatectomy have been enrolled and randomized to receive tadalafil 5 mg daily or placebo for 12 weeks. All subjects underwent a visit at baseline (V0) and after 12 weeks of treatment (V1), in which they filled the questionnaires NIH-CPSI (evaluation of prostatitis-like symptoms) and IPSS (lower urinary tract symptoms). Moreover, a trans-rectal ultrasound (TRUS) was performed during each visit. After completing these procedures, patients were admitted to Surgery Division for the execution of prostatectomy and the surgical specimens collected were used for the molecular analysis by RT-PCR. Tadalafil reduced significantly the NIH-CPSI pain and total score (estimated mean difference (EMD)= -1.9[-3.3;-0.6, p=0.004 and -11.6[-16.1; -7.2],p<0.0001; respectively), and IPSS voiding subdomain score (EMD= -1.2[-2.4; -0.1],p=0.04). The study of the ultrasonographic characteristics showed that, despite a non-significant change in prostate total volume, tadalafil has been able to prevent the growth of the prostatic adenoma and of intraprostatic calcifications, as well as to reduce the proportion of subjects with inhomogeneity in the prostatic echotexture. Moreover, tadalafil significantly decreased total cholesterol and triglycerides levels as well as waist circumference. The molecular analysis showed that tadalafil induces an anti-inflammatory effect, promotes tissue remodelling and inhibits stromal trans-differentiation towards a fibroblast phenotype. This randomized, double-blind and placebo-controlled clinical trial demonstrates that the in vivo treatment with tadalafil, in patients waitlisted for surgical treatment for BPH, has an antiinflammatory effect in the prostate associated with an improvement of LUTS. This is proven by the improvement in several markers of prostatic inflammation, including prostatitis-like symptoms, ultrasound markers of prostatitis and gene-expression of inflammatory markers within the prostate. none