Deleterious Effects Of Antidepressants On Semen Parameters: A Case Report

Khaled Shehatto, MD, Manal Abed, MD, Ahmed Elaghoury*, MDAbbassia Hospital for Mental Health, Cairo, Egypt

REFERENCES:1. Aronson J.K. MA DPhil MBChB FRCP HonFBPhS HonFFPM, Mechanistic and clinical

descriptions of adverse drug effects, adverse drug reactions, and drug interactions, Meyler'sSide Effects of Drugs (16th Ed), edited by Aronson J.K. MA DPhil MBChB FRCP HonFBPhSHonFFPM, 2016, Pages xxiii-xxvi

2. Attia, S. M., & Bakheet, S. A. (2013). Citalopram at the recommended human doses afterlong-term treatment is genotoxic for male germ cell. Food and chemical toxicology, 53, 281-285.

3. Elnazer, H. Y., & Baldwin, D. S. (2014). Treatment with citalopram, but not with agomelatine,adversely affects sperm parameters: a case report and translational review. Actaneuropsychiatrica, 26(2), 125-129.

4. Erdemir, F., Atilgan, D., Firat, F., Markoc, F., Parlaktas, B. S., & Sogut, E. (2014). The effect ofsertraline, paroxetine, fluoxetine and escitalopram on testicular tissue and oxidative stressparameters in rats. International braz j urol, 40(1), 100-108.

5. Evans-Hoeker E.A.,Eisenberg E.,Legro R.S.,Diamond M.P.,Steiner A.Z., Depressivesymptoms, antidepressant use and fertility treatment outcomes, Fertility and Sterility,Volume 108, Issue 3, 2017, Pages e298-e299

6. Hall Elise M.D.,Burt Vivien K. M.D. Ph.D., Male fertility: psychiatric considerations,Fertility and Sterility, Volume 97, Issue 2, 2012, Pages 434-439

7. Hendrick V, Gitlin M, Altshuler L, Korenman S. Antidepressant medications,mood and malefertility. Psychoneuroendocrinology. 2000 Jan;25(1):37-51. Review. PubMed PMID:10633534.

8. Impact of Duloxetine on Male Fertility. NCT03038867, Submitted in 20179. Jalali, A. S. (2017). Antidepressants and Male Infertility: Involvement of Spermatogonial

Stem Cells Self-renewal Disruption. J. stem cell Bio. transplant, 1, 1.10.Jannini, E. A., Ciocca, G., Limoncin, E., Mollaioli, D., Di Sante, S., Gianfrilli, D., ... & Lenzi, A.

(2015). Premature ejaculation: old story, new insights. Fertility and sterility, 104(5), 1061-1073.

11.Koyuncu, H., Serefoglu, E. C., Ozdemir, A. T., & Hellstrom, W. J. (2012). Deleterious effects ofselective serotonin reuptake inhibitor treatment on semen parameters in patients withlifelong premature ejaculation. International journal of impotence research, 24(5), 171.

12.Koyuncu, H., Serefoglu, E. C., Yencilek, E., Atalay, H., Akbas, N. B., & Sarica, K. (2011).Escitalopram treatment for premature ejaculation has a negative effect on semenparameters. International journal of impotence research, 23(6), 257.

13.Nørr, L., Bennedsen, B., Fedder, J., & Larsen, E. R. (2016). Use of selective serotoninreuptake inhibitors reduces fertility in men. Andrology, 4(3), 389-394.

14.Ozbek, E., Otunctemur, A., Simsek, A., Polat, E. C., Ozcan, L., Köse, O., & Cekmen, M. (2014).Genetic polymorphism in the serotonin transporter gene-linked polymorphic region andresponse to serotonin reuptake inhibitors in patients with premature ejaculation. Clinics,69(11), 710-713.

15.Pourmasumi, S., Sabeti, P., Rahiminia, T., Mangoli, E., Tabibnejad, N., & Talebi, A. R. (2017).The etiologies of sperm DNA abnormalities in male infertility: An assessment and review.Iranian Journal of Reproductive Medicine, 15(6), 331.

16.Relwani, R., Berger, D., Santoro, N., Hickmon, C., Nihsen, M., Zapantis, A., ... & Jindal, S.(2011). Semen parameters are unrelated to BMI but vary with SSRI use and prior urologicalsurgery. Reproductive Sciences, 18(4), 391-397.

17.Riggin, L., & Koren, G. (2015). Effects of selective serotonin reuptake inhibitors on spermand male fertility. Canadian Family Physician, 61(6), 529-530.

18.Safarinejad, M. R. (2007). Safety and efficacy of escitalopram in the treatment of prematureejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study. Journal ofclinical psychopharmacology, 27(5), 444-450.

19.Safarinejad, M. R. (2008). Sperm DNA damage and semen quality impairment aftertreatment with selective serotonin reuptake inhibitors detected using semen analysis andsperm chromatin structure assay. The Journal of urology, 180(5), 2124-2128.

20.Semen abnormalities with SSRI antidepressants. Prescrire Int. 2015 Jan;24(156):16-7.PubMed PMID: 25729824.

21.SSRI Effects on Semen Parameters in Men. NCT00385762, Submitted in 200622.Takeshima T, Kuroda S, Kobayashi M, Kato Y, Yumura Y, Noguchi K, Iwasaki A. [A case of male

infertility caused by drug-induced hyperprolactinemia]. Hinyokika Kiyo. 2013 Jan;59(1):65-7.Japanese. PubMed PMID: 23412129.

23.Tanrikut Cigdem,Schlegel Peter N., Antidepressant-Associated Changes in SemenParameters, Urology, Volume 69, Issue 1, 2007, Pages 185.e5-185.e7

Email: drkhaled06@hotmail.com

PS: The authors have seen three cases with definitive antidepressant-induced male fertility problems. The case presented here is a coauthor (AE), not the onesubmitted by leading author (KS) in the abstract. Due to major health condition along the past few months, KS was unable to edit the submitted case report for finalpublication. Please, be in contact (Email: drkhaled06@hotmail.com) to know the further details of the case.

▪ “Definitive case report” has been suggested as a concept for the strong evidence of adverse drug effects. One mechanism ofthe definitive case report is the evidence of cell disruption, whether structurally or physiologically. (1)

▪ Many antidepressants (AD) esp., serotonin reuptake inhibitors (SRI) have been observed to be associated with fertilityproblems in male patients, in addition to the well-known adverse sexual dysfunction: anorgasmia, erectile dysfunction,decreased libido.

▪ Preclinical animal studies showed the harmful effects of SRI on sperm parameters and DNA structure. (4)▪ Males with fertility problems are highly comorbid with both premature ejaculation (PE) and depression/anxiety.▪ AD are commonly prescribed for PE (10,12), plus their use in depression/anxiety symptoms comorbid with male infertility.▪ Is it a Confounding by indication? Depression itself may harm the sperm parameters, NOT the AD. However, this can be

questioned in many cases observed with the temporal relationship between the onset of AD therapy and fertility problems,plus their improvement after AD discontinuation. (5,6,7)

▪ What are the specific mechanisms of AD harm on sperms? (9) Are they short term / long term? Are they reversible or not?Are questions under current investigations. For example there are two unpublished studies about this clinical problemsponsored by the Weill Medical College of Cornell University, US. One is completed with results (21), and the other is stillongoing (8).

▪ Sulpiride is approved for depression in some countries (Germany and Japan), with reported cases of secondary infertility dueto the hyperprolactinemia. This problem needs caution when an antipsychotic is used as an augmentation of AD therapy. (22)

▪ Citalopram and its enantiomer escitalopram have special warning and dose-related observations due to their genotoxiceffects on sperm. (2,3,18,20).

Case report:➢ A 49 yo man with moderate, mixed anxiety-depression disorder, was put

on paroxetine for four years.

➢ Secondary infertility was observed for the last two years, which is

currently followed up by an andrologist.

➢ The patient does not suffer any other medical conditions, including

varicocele.

➢ He is trying to get children with his wife along the past three years.

➢ Paroxetine was discontinued, and followup with andrology is still

running.

RECOMMENDATIONS:❖Long-term AD use with male patients suffering

from fertility problems needs clinical caution

and close follow-up of sperm parameters.

❖Pharmacologically speaking, AD have a

definitive disruptive effect on spermatogenesis,

which cannot be undermined by the few

published data.

❖The same problem has been observed with

antipsychotic augmentation due to

hyperprolactinemia.

❖Observations with citalopram and escitalopram

are more than other AD.