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 (TAD) 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 TAD 5 mg/daily (OAD-TAD; n=23) or 20 mg on-demand (OD-TAD; n=20) for 2 months. Primary outcomes were variations of body composition measured by DEXA; 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. ED and LUTS 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 C2C12 cells upon increasing TAD concentrations (10-7-10-6M) increased total androgen receptor (AR) mRNA and protein expression as well as myogenin protein expression after 24 and 72 hours (2.8±0.4-fold and 1.4±0.02-fold vs control, respectively, p<0.05). Conclusions: Daily TAD 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 AR protein expression in skeletal muscle cells suggests a translational action of phosphodiesterase type-5 on this receptor.
Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization
Fittipaldi S;Bimonte VM;Crescioli C;Di Luigi L;Lenzi A;Migliaccio S.
2017-01-01
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 (TAD) 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 TAD 5 mg/daily (OAD-TAD; n=23) or 20 mg on-demand (OD-TAD; n=20) for 2 months. Primary outcomes were variations of body composition measured by DEXA; 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. ED and LUTS 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 C2C12 cells upon increasing TAD concentrations (10-7-10-6M) increased total androgen receptor (AR) mRNA and protein expression as well as myogenin protein expression after 24 and 72 hours (2.8±0.4-fold and 1.4±0.02-fold vs control, respectively, p<0.05). Conclusions: Daily TAD 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 AR protein expression in skeletal muscle cells suggests a translational action of phosphodiesterase type-5 on this receptor.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
