The Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia

ContextClinical trials of phosphodiesterase type 5 inhibitors (PDE5-Is) have consistently demonstrated a significant reduction in lower urinary tract symptoms (LUTS) and small urinary flow rate changes in men with benign prostatic hyperplasia (BPH).ObjectiveThis review presents the proposed mechanisms of action of PDE5-Is in the treatment of BPH-LUTS focusing on the localization of PDE5 isoenzymes in the pelvic structures; smooth muscle relaxation in the bladder, prostate, and supporting vasculature; increased blood perfusion of the bladder and prostate; and modulation of sensory impulses from these organs.Evidence acquisitionLiterature describing in vitro, preclinical, or clinical studies of pathologic processes contributing to LUTS or effects of PDE5 inhibition on the lower urinary tract (LUT) was selected for review.Evidence synthesisWe objectively assessed and summarized the published data focusing on articles published within the past 10 yr. Articles before the time cut-off were included if historically relevant.ConclusionsThe PDE5 isoenzymes are highly expressed in the LUT including the bladder, prostate, and their supporting vasculature. In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. In animals characterized by ischemia/hypoxia of the genitourinary tract, treatment with PDE5-Is increases bladder and prostate tissue oxygenation. PDE5-Is have been shown to reduce nonvoiding contractions and bladder afferent nerve firing in decerebrate spinal cord–injured rats, and to reduce mechanosensitive afferent activities of both Aδ- and C-fibers in an irritated or overextended bladder model.