Is there a rationale for the chronic use of phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia?
OBJECTIVE
To critically review the physiological roles of phosphodiesterase-5 (PDE5), to explain and support the putative impact and clinical significance of PDE5 inhibitors (PDE5-Is) in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both highly prevalent in men aged > or =50 years, as PDE5-Is are very effective as a first-line therapy for ED, and attractive for further physiological functional investigations.


METHODS
We searched Medline for peer-reviewed articles in English, from 1991 to 2008, to provide a critical contemporary review of PDE5 pertaining to the potential interest of findings supporting a role for PDE5-Is in LUTS due to BPH. The selection of papers was based on the relevance of subject matter. A critical analysis of available fundamental and clinical data is reported.


RESULTS
Several studies assessed the role of the nitric oxide/cGMP signalling pathway in the regulation of the prostate tone, with the support of clinical observations. PDE5-Is can also represent a potential mode of action allowing the targeting of transcriptional activity implicated in the regulation of the progression of the inflammatory process involved in BPH. PDE5-Is can inhibit human stromal cell proliferation of the prostate mediated by cGMP accumulation. New targeting hypotheses of pathophysiological processes are also reported.


CONCLUSIONS
There is evidence that LUTS and ED are strongly linked. This analysis of the regulatory basis of PDE5 biology could indicate several directions of investigation. However, it is necessary to devise well-designed large prospective studies that would produce significant data before this approach becomes a standard of care.
Roumeguère
Thierry
T
Laboratory of Experimental Medicine, CHU Charleroi, ULB, Montigny -le -Tilleul, Belgium. thierry.roumeguere@ulb.ac.be
Zouaoui Boudjeltia
K
K
Hauzeur
Claude
C
Schulman
Claude
C
Vanhaeverbeek
Michel
M
Wespes
Eric
E
D000368:Aged; D002243:Carbolines / Q000008:administration & dosage / Q000009:adverse effects; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011470:Prostatic Hyperplasia / Q000150:complications*; D053448:Prostatism / Q000188:drug therapy* / Q000209:etiology; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects; D000068581:Tadalafil; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects; D000069058:Vardenafil Dihydrochloride
D002243:Carbolines; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011799:Quinazolines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; C047638:alfuzosin; D000068677:Sildenafil Citrate