Relationship Between Chronic Tadalafil Administration and Improvement of Endothelial Function in Men With Erectile Dysfunction: A Pilot Study

Int J Impot Res. Mar-Apr 2007;19(2):200-7. doi: 10.1038/sj.ijir.3901513. Epub 2006 Aug 31.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Carbolines / administration & dosage*
  • Carbolines / therapeutic use
  • Carotid Arteries / anatomy & histology
  • Carotid Arteries / drug effects
  • Cross-Over Studies
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Erectile Dysfunction / drug therapy*
  • Humans
  • Insulin / blood
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Middle Aged
  • Penis / blood supply
  • Penis / drug effects
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Phosphodiesterase Inhibitors / therapeutic use
  • Pilot Projects
  • Tadalafil
  • Treatment Outcome
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vasodilation


  • Biomarkers
  • Carbolines
  • Endothelin-1
  • Insulin
  • Phosphodiesterase Inhibitors
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Tadalafil
  • C-Reactive Protein