An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study.
OBJECTIVE
Assess the effects on spermatogenesis of daily tadalafil 20mg over three spermatogenesis cycles in men >or= 45 yr.


METHODS
In this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20mg (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 >or= 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 >or= 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 >or= 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 20mg on spermatogenesis or hormones related to testicular function in men >or= 45 yr.
Hellstrom
Wayne J G
WJ
Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA. whellst@tulane.edu
Gittelman
Marc
M
Jarow
Jonathan
J
Steidle
Christopher
C
McMurray
James
J
Talley
David
D
Watts
Steven
S
Mitchell
Carol L
CL
McGill
James M
JM
D002243:Carbolines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D007172:Erectile Dysfunction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D012661:Semen / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology*; D000068581:Tadalafil; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D013739:Testosterone; D000068581:Tadalafil; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone