The effect of 5α reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men

Context: Dutasteride and finasteride are 5 alpha-reductase inhibitors (5ARIs) that dramatically reduce serum levels of dihydrotestosterone (DHT). Objective: Because 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 (D; 0.5 mg) (n = 33), finasteride (F; 5 mg) (n = 34), or placebo (n = 32) once daily for 1 yr. Main Outcome Measures: Blood and semen samples were collected at baseline and 26 and 52 wk of treatment and 24 wk after treatment and were assessed for T, DHT, and semen parameters. Results: D and F significantly (P < 0.001) suppressed serum DHT, compared with placebo (D, 94%; F, 73%) and transiently increased serum T. In both treatment groups, total sperm count, compared with baseline, was significantly decreased at 26 wk (D, -28.6%; F, -34.3%) but not at 52 wk (D, -24.9%; F, -16.2%) or the 24-wk follow-up (D, -23.3%; F, -6.2%). At 52 wk, 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 to 12% in sperm motility during treatment with both D and F 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.