title: Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study.
abstract: Men with erectile dysfunction (ED) frequently have a disproportionate burden of comorbid vascular disorders including atherosclerotic disease. We investigated whether scheduled tadalafil is better than on-demand (OD) in improving endothelium-dependent vasodilatation of cavernous arteries in men with ED and whether this effect is also exerted on markers of endothelial function. We did an open-label, randomized, crossover study including 20 male outclinic patients aged 18 years or older (mean age 54 years) who had at least a 3-month history of ED of any severity or etiology. Tadalafil (20 mg) on alternate days (ADs) or OD was administered for 4 weeks. Primary end points were variations of basal inflow (peak systolic velocity (PSV)) and flow-mediated dilatation (FMD) of cavernous arteries compared with baseline at penile Duplex ultrasound. Secondary end points were variations of Q13-SIEDY scores regarding morning erections and of markers of endothelial function, that is, vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule, endothelin-1 (ET-1), insulin and C-reactive protein (CRP). PSVs and FMD were higher after AD treatment when compared with OD and baseline, respectively (P=0.0001), and improvements were maintained from 2 weeks after discontinuation (P<0.005). Patients receiving tadalafil AD experienced a significant improvement of morning erections as compared to AD treatment (P<0.0001); ET1, VCAM and CRP showed a robust decrease after chronic vs OD regimes (P<0.05), with concomitant increase in insulin levels (P<0.05), without any variation in blood pressure and other laboratory parameters. Chronic but not OD tadalafil improves endothelial function with sustained effects from its discontinuation. Chronic treatment also produces a dramatic increase in morning erections, which determines better oxygenation to the penis, thus providing a rationale for vascular rehabilitation.
authors.affiliation: Medical Pathophysiology, University of Rome La Sapienza, Rome, Italy. antonio.aversa@uniroma1.it
authors.forename: A
authors.initials: A
authors.lastname: Aversa
authors.forename: E
authors.initials: E
authors.lastname: Greco
authors.forename: R
authors.initials: R
authors.lastname: Bruzziches
authors.forename: M
authors.initials: M
authors.lastname: Pili
authors.forename: G
authors.initials: G
authors.lastname: Rosano
authors.forename: G
authors.initials: G
authors.lastname: Spera
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002243:Carbolines / Q000008:administration & dosage* / Q000627:therapeutic use; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000187:drug effects; D018592:Cross-Over Studies; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010413:Penis / Q000098:blood supply / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D010865:Pilot Projects; D000068581:Tadalafil; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D002243:Carbolines; D019332:Endothelin-1; D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000068581:Tadalafil; D002097:C-Reactive Protein