Impact of duloxetine on male fertility: A randomised controlled clinical trial

Andrologia. 2021 Nov;53(10):e14207. doi: 10.1111/and.14207. Epub 2021 Aug 9.


This study assessed the impact of duloxetine (serotonin and norepinephrine reuptake inhibitor) on semen parameters, sperm DNA fragmentation and serum hormones. We performed a double-blind, placebo-controlled, randomised clinical trial of duloxetine 60mg or placebo daily for 6 weeks (5 weeks full dose and 1 week taper). The primary outcome was the proportion of men with abnormal DNA fragmentation during and after duloxetine administration. Secondary outcomes were changes in semen parameters and hormones on treatment (2 and 6 weeks) and after discontinuation (8 and 10 weeks). Sixty-eight healthy males aged 18-65 were included. Duloxetine was not associated with an increase in the proportion of participants with abnormal sperm DNA fragmentation terminal deoxynucleotidyl transferase dUTP nick-end labelling scores (>25%) on treatment (p = 0.09) or after treatment (p = 0.56), nor did median sperm DNA fragmentation increase on treatment. Compared with placebo, there were no changes in bulk semen parameters during treatment. Limited changes in hormonal values were detected. This first published human study of a serotonin and norepinephrine reuptake inhibitor on male fertility revealed no clinically meaningful effects on sperm DNA fragmentation, semen parameters or serum hormones. Duloxetine, and possibly other serotonin and norepinephrine reuptake inhibitors, may be considered for men desiring fertility who require antidepressant treatment.

Keywords: DNA fragmentation; SNRIs; duloxetine; semen parameters.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antidepressive Agents*
  • DNA Fragmentation
  • Double-Blind Method
  • Duloxetine Hydrochloride
  • Fertility
  • Humans
  • Male
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Spermatozoa*


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Duloxetine Hydrochloride