title: Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization.
abstract: OBJECTIVE
  Phosphodiesterase type-5 inhibitor administration in diabetic men with erectile dysfunction (ED) is associated with reduced waist circumference. We evaluated potential effects of daily tadalafil administration on body composition and investigated its possible mechanism(s) of action in C2C12skeletal muscle cells in vitro.
  
  
  METHODS
  Forty-three men on stable caloric intake (mean age 48.5 ± 7; BMI 25.5 ± 0.9 kg/m2) complaining mild ED and/or low urinary tract symptoms (LUTS) were randomly assigned to receive tadalafil (TAD) 5 mg/daily (once-a-day=OAD-TAD; n = 23) or 20 mg on-demand (on-demand=OD-TAD; n = 20) for 2 months. Primary outcomes were variations of body composition measured by Dual-energy X-ray absorptiometry; secondary outcomes were ED/LUTS questionnaire scores along with hormone (testosterone, estradiol, insulin) and endothelial function (Endopat2000) variations.
  
  
  RESULTS
  OAD-TAD increased abdominal lean mass (p < 0.01) that returned to baseline after 2 months withdrawal. LUTS scores improved (p<0.01) in OD-TAD while ED scores improved (p < 0.01) in both groups. We found significant improvements in endothelial function (p < 0.05) that directly correlated with serum insulin (p < 0.01; r = 0.3641) and inversely correlated with estradiol levels (p < 0.01; r = 0.3655) even when corrected for potential confounders. Exposure of C2C12cells upon increasing tadalafil concentrations (10-7to 10-6M) increased total androgen receptor mRNA and protein expression as well as myogenin protein expression after 24 and 72 h (2.8 ± 0.4-fold and 1.4 ± 0.02-fold vs. control, respectively, p < 0.05).
  
  
  CONCLUSIONS
  Daily tadalafil improved lean mass content in non-obese men probably via enhanced insulin secretion, estradiol reduction, and improvement of endothelial function in vivo. The in vitro increased myogenin and androgen receptor protein expression in skeletal muscle cells suggests a translational action of phosphodiesterase type-5 on this receptor.
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy. aversa@unicz.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Aversa
authors.affiliation: IRCCS SDN, Napoli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fittipaldi
authors.affiliation: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Francomano
authors.affiliation: Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Rome, Italy.
authors.forename: Viviana M
authors.initials: VM
authors.lastname: Bimonte
authors.affiliation: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, "Sapienza" University of Rome, Rome, Italy.|LiSa Laboratory, Policlinico Catania, University of Catania, Catania, Italy.
authors.forename: Emanuela A
authors.initials: EA
authors.lastname: Greco
authors.affiliation: Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Rome, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Crescioli
authors.affiliation: Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Luigi
authors.affiliation: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Department of Movement, Human and Health Sciences, Section of Health Sciences, "Foro Italico" University of Rome, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Migliaccio
mesh_terms: D050153:Abdominal Fat / Q000000981:diagnostic imaging / Q000187:drug effects*; D015502:Absorptiometry, Photon; D000328:Adult; D001823:Body Composition / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004958:Estradiol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018008:Myogenin / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011944:Receptors, Androgen / Q000378:metabolism; D000068581:Tadalafil / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007328:Insulin; D018008:Myogenin; D058986:Phosphodiesterase 5 Inhibitors; D011944:Receptors, Androgen; D004958:Estradiol; D000068581:Tadalafil
keywords: Androgen receptor; Erectile Dysfunction; Estradiol; Fat mass; Lower Urinary Tract Symptoms; Phosphodiesterase type-5; Skeletal muscle; Testosterone