Is treatment of men with cyclosporine associated with reduced fertility? Is cyclosporine teratogeni

Fråga: Is treatment of men with cyclosporine associated with reduced fertility? Is cyclosporine teratogenic by toxic action on sperms or spermatogenesis?

Background: A 35-year-old man with an unclear, systemic inflammatory disease will start treatment with cyclosporine. However, the patient now attempts to father a child and wonders about negative effects by cyclosporine on male fertility.

Sammanfattning: Even though the literature is rather limited, the conclusion is that there is no convincing data suggesting that cyclosporine would reduce male fertility. In addition, there is nothing to suggest that cyclosporine would have teratogenic effect on spermatogenesis or mature sperm cells.

Svar: Despite a thorough literature search, surprisingly little information was found on the topic in relation to the wide-spread use of this important immunosuppressant. Early reports on small cohorts have not shown any reduced fertility in male patients treated with cyclosporine (1-3). However, it was later stated in one report that among infertile male renal transplant patients, lower levels of sperms with normal motility were found, as compared to fertile renal transplant patients, and among these non-fertile men a correlation between abnormal sperm counts to high cyclosporine blood levels was claimed (4, 5). No confirmation of this finding has been found in the literature, though. Experiments performed in vitro indicate that extremely high exposure to cyclosporine will reduce sperm motility, but this effect was only seen at concentrations exceeding therapeutic blood concentrations almost 1000-fold (6). No report on reduced male fertility was found in the Swedish adverse drug reactions register (7).

Regarding possible teratogenic effects of cyclosporine, there is no signal in the Medical Birth Register meaning that women exposed to cyclosporine during pregnancy do not have an increased risk of delivering children with malformations (8, 9). This is a strong argument against a teratogenic effect of cyclosporine on male gametes. Furthermore, a toxic effect on sperm cells is believed to have dramatic impact on the chances of successful oocyte fertilization and embryo survival primarily, rather than risk of malformations (10, 11).

Taken together, based on the current knowledge about cyclosporine, treatment with this immunosuppressant is not considered to reduce fertility in male patients. Admittedly, the literature is surprisingly rather limited and the issue is complicated to study. It is important to consider the underlying disease and to what extent this may have an impact on the chances to successfully father a child, and also take into account possible effects of other drugs used or considered for use by the patient in question. Haberman J, Karwa G, Greenstein SM, Soberman R, Glicklich D, Tellis V, Melman A. Male fertility in cyclosporine-treated renal transplant patients. J Urol. 1991;145:294-6 (abstract). Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Intern Med. 2000;160:610-9. Drugline no 04181 (year 1984) Eid MM, Abdel-Hamid IA, Sobh MA, el-Saieded MA. Assessment of sperm motion charactersitcis in infertile renal transplant recipients using computerized analysis. Int J Androl 1996;19(6):338-44 (abstract). RELIS database Misro MM, Chaki SP, Srinivas M, Chaube SK. Effect of cyclosporine on human sperm motility in vitro. Arch Androl 1999;43(3):215-220

SWEDIS, the Swedish adverse drug reactions register
http://www.janusinfo.se/gravXML/template/substancePrn.xml?search
Drugline no 23462 (year 2008)
http://www.janusinfo.se/gravreg/index.asp?file=bakgrund.xml

www.toxbase.org