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Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: Pathophysiology and mechanism(s) of action
Author(s) -
Andersson KarlErik,
de Groat William C.,
McVary Kevin T.,
Lue Tom F.,
Maggi Mario,
Roehrborn Claus G.,
Wyndaele Jean Jacques,
Melby Thomas,
Viktrup Lars
Publication year - 2011
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20999
Subject(s) - medicine , tadalafil , lower urinary tract symptoms , pathophysiology , cgmp specific phosphodiesterase type 5 , cyclic guanosine monophosphate , urinary system , hyperplasia , urology , erectile dysfunction , nitric oxide , prostate , cancer
Background The PDE5 inhibitor tadalafil is investigation for the treatment of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Several clinical studies of tadalafil and other PDE5 inhibitors have reported significant symptom reduction but limited urinary flow rate improvement. This manuscript reviews the published literature describing the pathophysiology of male LUTS, with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition. Methods Literature (through March 2010) was obtained via Medline searches and from the individual reviewers files. Articles were selected for review based on describing in vitro, preclinical, or clinical studies of pathological processes contributing to LUTS, or possible effects of PDE5 inhibition in the lower urinary tract. Results Major mechanisms contributing to LUTS include: reduced nitric oxide/cyclic guanosine monophosphate signaling; increased RhoA kinase pathway activity; autonomic overactivity; increased bladder afferent activity; and pelvic ischemia. Tadalafil and other PDE5 inhibitors have demonstrated beneficial effects on smooth muscle relaxation, smooth muscle and endothelial cell proliferation, nerve activity, and tissue perfusion that may impact LUTS in men. Conclusions The pathophysiology of male LUTS is complex and not completely understood. LUTS may occur independently of BPH or secondary to BPH but in both cases involve obstructive or irritative mechanisms with substantial pathophysiological overlap. While the precise mechanism remains unclear, inhibition of PDE5 seems to have an effect on several pathways that may impact LUTS. Neurourol. Urodynam. 30:292–301, 2011. © 2011 Wiley‐Liss, Inc.