Effect of antidepressant medications on semen parameters and male fertility

Abstract

Antidepressant medications are commonly used in males of reproductive age for long‐term treatment of depression, as well as other disorders. Although antidepressants are known to be associated with sexual side‐effects, their effects on semen parameters and other markers of male fertility have been less thoroughly described. The majority of available studies have focused on selective serotonin reuptake inhibitors, which have been shown to negatively impact semen quality in in vitro, animal and human studies. Fluoxetine, in particular, has been the subject of multiple studies and has been associated with gonadotoxic effects, including decreased sperm concentration and motility, increased deoxyribonucleic acid fragmentation, and decreased reproductive organ weights. Studies of several other selective serotonin reuptake inhibitors have yielded similar results. Reassuringly, this effect does seem to be reversible. The data regarding serotonin–norepinephrine reuptake inhibitors, norepinephrine–dopamine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors and atypical antidepressants are sparse, varied and conflicting. Given the widespread and often long‐term use of antidepressant medications, there is a clear need for further data regarding their impact on semen quality and male fertility.

The antidepressant Sertraline inhibits CatSper Ca2+ channels in human sperm

“…Among other factors, such previously unexplored side effects of commonly used drugs might be involved in the adverse trends in human reproduction and increasing demand for assisted reproduction ( Skakkebaek et al , 2016 ). Supporting this notion, previous studies suggested that SSRIs reduce male fertility by affecting semen quality (reviewed by Norr et al , 2016 ; Sylvester et al , 2019 ; Beeder and Samplaski, 2020 ). Treatment of rodents with SSRIs reduced the sperm count, sperm motility, testicular weight, length of seminiferous tubules, and, thereby, male fertility ( Bataineh and Daradka, 2007 ; Attia, and Bakheet, 2013 ; Monteiro Filho et al , 2014 ; Galal et al , 2016 ; Lyons et al , 2016 ; Atli et al , 2017 ).…”

“…In men, intake of SSRIs was associated with reduced sperm concentration, a higher number of morphologically abnormal sperm, and an increase in DNA fragmentation. In most of these studies, recovery of normal semen parameters was observed upon cessation of SSRI intake ( Kumar et al, 2006 ; Tanrikut and Schlegel, 2007 ; Safarinejad, 2008 ; Tanrikut et al , 2010 ; Koyuncu et al , 2011 ; Relwani et al , 2011 ; Akasheh et al , 2014 ; Elnazer and Baldwin, 2014 ; Beeder and Samplaski, 2020 ). Whether the intake of SSRIs affects female fertility and/or IVF success is unclear and, in fact, a much-debated question ( Klock et al , 2004 ; Friedman et al , 2009 ; Domar et al , 2013 ; Casilla-Lennon et al , 2016 ; Evans-Hoeker et al , 2018 ; Sylvester et al , 2019 ).…”

Reply to Letter to the Editor by Derakhshan et al. (2021) ‘Vagal nerve stimulation for the treatment of male factor infertility’

“…This indicates that forced manipulation of 5‐HT by VNS may indeed be counterproductive in treating male infertility. The Beeder and Samplaski (2020) study, also referred to by the authors, links anti‐depressants, especially the class of SSRIs (selective serotonin reuptake inhibitors), which act by inhibiting the reuptake of 5‐HT, thereby inducing increased plasma concentrations of 5‐HT, with male infertility. As it is always circumspect to suggest that correlation is equivalent to cause, this study shows that SSRIs increase 5‐HT, but the treatments also caused increased oxidative stress and apoptosis in the testes, decreased FSH, LH, testosterone and oestrogen levels.…”

Vagal nerve stimulation for the treatment of male factor infertility

“…The increase in 5-HT within the normal range is connected with the sperm motility improvement, suggesting that it has a physiologic role (Gonzales et al, 1989). Taking selective serotonin reuptake inhibitor (SSRI) was observed to produce a damaging effect on semen quality and increase oxidative stress in the male reproductive system, suggesting the importance of 5-HT in males reproductivity (Beeder & Samplaski, 2020).…”