Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization.
Level 2 - randomized trial
Randomized controlled trial in humans accompanied by in vitro mechanistic work
PubMed 28133708 · doi:10.1007/s12020-016-1208-y
What was done
Forty-three nonobese men (mean age 48.5 ± 7 years; BMI 25.5 ± 0.9 kg/m²) with mild erectile dysfunction (ED) and/or lower urinary tract symptoms (LUTS) on stable caloric intake were randomized to receive tadalafil 5 mg daily (n = 23) or 20 mg on-demand (n = 20) for 2 months. Primary outcomes were body composition changes measured by dual-energy X-ray absorptiometry (DXA); secondary outcomes were ED/LUTS questionnaire scores, hormone levels (testosterone, estradiol, insulin), and endothelial function (EndoPAT2000). Mechanism of action was evaluated in vitro in C2C12 skeletal muscle cells exposed to tadalafil (10⁻⁷ to 10⁻⁶ M).
What was found
Daily tadalafil significantly increased abdominal lean mass (p < 0.01), which returned to baseline 2 months after withdrawal. ED scores improved significantly in both groups (p < 0.01), whereas LUTS scores improved in the on-demand group (p < 0.01). Endothelial function improved (p < 0.05), correlating directly with serum insulin (r = 0.3641, p < 0.01) and inversely with estradiol (r = 0.3655, p < 0.01). In C2C12 cells, tadalafil increased androgen receptor mRNA and protein, as well as myogenin protein expression at 24 and 72 hours (2.8 ± 0.4-fold and 1.4 ± 0.02-fold vs. control, respectively, p < 0.05).
Why it matters
These findings suggest daily PDE5 inhibition may promote lean mass accretion and improve vascular function beyond standard urological symptom relief.
Limits
The clinical sample was small (n = 43) and lacked an inert placebo comparison group (comparing daily to on-demand dosing only). Specific numeric values for lean mass changes and hormone levels were omitted in the abstract, and follow-up was limited to a 2-month intervention and 2-month withdrawal.
Cited by
- partial Tadalafil upregulates either the sensitivity or the number of androgen receptors, enhancing the body's response to circulating testosterone.