Efficacy of Selenium and/or N-Acetyl-Cysteine for Improving Semen Parameters in Infertile Men: A Double-Blind, Placebo Controlled, Randomized Study (Publication with Expression of Concern)

Purpose: We explored the efficacy of selenium and/or or N-acetyl-cysteine for improving semen parameters in infertile men, and the associations among semen quality and the concentrations of selenium and N-acetyl-cysteine in seminal plasma. Materials and Methods: The study included 468 infertile men with idiopathic oligo-asthenoteratospermia who were randomized to receive 200 mu g selenium orally daily (selenium group of 116), 600 mg N-acetyl-cysteine orally daily (N-acetyl-cysteine group of 118), 200 mu g selenium plus 600 mg N-acetyl-cysteine orally daily (selenium plus N-acetyl-cysteine group of 116) or similar regimen of placebo (control group of 118) for 26 weeks, followed by a 30-week treatment-free period. These patients provided blood samples for the measurement of serum testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, inhibin B, selenium and N-acetyl-cysteine. Semen samples were also obtained for routine semen analysis, and the measurement of seminal plasma selenium and N-acetyl-cysteine. Results: In response to selenium and N-acetyl-cysteine treatment serum follicle-stimulating hormone decreased but serum testosterone and inhibin B increased. All semen parameters significantly improved with selenium and N-acetyl-cysteine treatment. Administering selenium plus N-acetyl-cysteine resulted in additive beneficial effects. A significant positive correlation existed between the seminal plasma concentrations of selenium and N-acetyl-cysteine, and semen parameters. A strong correlation was observed between the sum of the selenium and N-acetyl-cysteine concentrations, and mean sperm concentration (r = 0.67, p = 0.01), sperm motility (r = 0.64, p = 0.01) and percent normal morphology (r = 0.66, p = 0.01). Conclusions: These results indicate that supplemental selenium and N-acetylcysteine improve semen quality. We advocate their use for male infertility treatment.