Context: Dutasteride and finasteride are 5-reductase inhibitors (5ARI) that dramatically reduce serum levels of dihydrotestosterone (DHT).

Objective: As androgens are essential for fertility, we sought to determine the impact of 5ARI administration on serum testosterone (T), DHT, and spermatogenesis.

Design, Setting, Subjects, and Intervention: We conducted a randomized, double-blinded, placebo-controlled trial in 99 healthy men randomly assigned to receive dutasteride (0.5 mg) (n = 33), finasteride (5 mg) (n = 34) or placebo (n = 32) once daily for 1 year.

Main Outcome Measures: Blood and semen samples were collected at baseline, at 26 and 52 weeks of treatment, and at 24 weeks post-treatment, and were assessed for T, DHT, and semen parameters.

Results: Dutasteride (D) and finasteride (F) significantly (P < 0.001) suppressed serum DHT compared with placebo (dutasteride, 94%; finasteride 73%), and transiently increased serum T. In both treatment groups, total sperm count compared to baseline was significantly decreased at 26 weeks (D -28.6%, F -34.3%) but not at 52 weeks (D -24.9%, F -16.2%) nor at the 24 week follow-up (D -23.3%, F -6.2%). At 52 weeks, semen volume was decreased (D -29.7%, F -14.5%, significantly for D) as was sperm concentration (D -13.2%, F -7.4%, neither significant). There was a significant reduction of 6-12% in sperm motility during treatment with both dutasteride and finasteride and at follow-up. Neither treatment had any effect on sperm morphology.

Conclusions: This study demonstrates that the decrease in DHT induced by 5ARIs is associated with mild decreases in semen parameters that appear reversible after discontinuation.