ABSTRACT
AIMS: This double-blind, randomized, four-period, two-way crossover study was conducted to evaluate the acute effects of oral sildenafil (100-mg single dose) on sperm motility, count, density, morphology and vitality as well as ejaculate volume and viscosity in healthy male subjects. The concentrations of sildenafil and its primary circulating metabolite UK-103,320 were measured in ejaculate and compared with those in plasma. The study also included assessments of safety and tolerability. METHODS: A total of 17 healthy male volunteers aged 19--34 years were randomized to receive a single 100-mg dose of sildenafil for two periods and a single dose of placebo for two periods, with each period separated by a minimum of 5--7 days. Sperm and ejaculate properties were evaluated from semen samples taken at screening and 1.5 h after dose. An additional semen sample was collected 4 h after dose, and drug and metabolite concentrations were measured in this sample and the sample taken 1.5 h after dose for comparison with plasma concentrations. Blood samples were collected before each dose and 0.25, 0.5, 1, 2, 3, 4 and 6 h after dose for measurement of sildenafil and metabolite concentrations. RESULTS: Sildenafil had no statistically significant effect on sperm motility, count or density; the percentage of abnormal sperm forms; or the percentage of living sperm. It also did not affect ejaculate volume or viscosity. All measures were within normal ranges. Sildenafil distributed into the semen rapidly, resulting in significant correlations between concentrations of sildenafil in the semen and total (R2=0.588) or free (R2=0.454) plasma concentrations (P<0.0001). Total semen concentrations of sildenafil were 18% of total plasma concentrations. UK-103,320 appeared to distribute more slowly from the plasma into the semen, resulting in a lack of correlation between semen and plasma concentrations. The amount of sildenafil and UK-103,320 in the ejaculate was small (< 2x10(-4)% of the administered dose at 1.5 h). Sildenafil was well tolerated; no patient withdrew from the study due to adverse events attributed to sildenafil. CONCLUSIONS: These results indicate that a single 100-mg oral dose of sildenafil does not have an adverse effect on sperm function or ejaculate quality.