An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20 mg: Results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study

Objectives: Assess the effects on spermatogenesis of daily tadalafil 20 mg over three spermatogenesis cycles in men >= 45 yr. Methods: in this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20 mg (n = 125) or placebo (n = 128) for 9 mo followed by a 6-mo, treatment-free period. Semen and serum samples were provided at baseline and every 10-12 wk. The primary outcome was the proportion of subjects with >= 50% reduction in sperm concentration at end point. Secondary outcomes included sperm concentration, number per ejaculate, motility and morphology; serum concentrations of testosterone, luteinizing and follicle-stimulating hormones; and tolerability. Results: Of 253 men enrolled, 191 (75%) completed treatment phase: 2 of 96 (2.1%, placebo) and 12 of 95 (12.6%, tadalafil) subjects had >= 50% reduction in sperm concentration. Tadalafil was noninferior to placebo because the upper 95% confidence interval for the difference in proportions of tadalafil and placebo subjects with a >= 50% reduction in sperm concentration was 17.5%, significantly less than the prespecified noninferiority margin of 20% (p = 0.015). Ninety-four percent (179 of 191) of men completed the 6-mo, treatment-free period: Baseline sperm concentration levels were restored in 8 of 12 (tadalafil) and 1 of 2 (placebo) men. There were no significant differences between groups in secondary end points. Common treatment-emergent adverse events were headache, back pain, dyspepsia, gastroesophageal reflux disease, and myalgia. Twelve (9.6%) tadalafil and seven (5.5%) placebo subjects discontinued because of adverse events. Conclusions: This study demonstrated no deleterious effects of 9 mo of daily tadalafil 20 mg on spermatogenesis or hormones related to testicular function in men >= 45 yr. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.