New Study
Endocrine. 2017 Jan 30. doi: 10.1007/s12020-016-1208-y. [Epub ahead of print]
Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization.
Aversa A1, Fittipaldi S2, Francomano D3, Bimonte VM4, Greco EA3,5, Crescioli C4, Di Luigi L4, Lenzi A3, Migliaccio S4.
1Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy. aversa@unicz.it.
2IRCCS SDN, Napoli, Italy.
3Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, “Sapienza” University of Rome, Rome, Italy.
4Department of Movement, Human and Health Sciences, Section of Health Sciences, “Foro Italico” University of Rome, Rome, Italy.
5LiSa Laboratory, Policlinico Catania, University of Catania, Catania, Italy.
Abstract
PURPOSE:
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 C2C12 skeletal 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 (p0.01) that returned to baseline after 2 months withdrawal. LUTS scores improved (p0.01) in OD-TAD while ED scores improved (p0.01) in both groups. We found significant improvements in endothelial function (p0.05) that directly correlated with serum insulin (p0.01; r=0.3641) and inversely correlated with estradiol levels (p0.01;r=0.3655) even when corrected for potential confounders. Exposure of C2C12 cells upon increasing tadalafil concentrations (10-7 to 10-6 M) 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, p0.05).
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.
Comments