Avoiding Toxins Including Spermatotoxic Medications

Gillian Stearns, MD; Paul J. Turek, MD

Disclosures

Semin Reprod Med. 2013;31(4):286-292. 

In This Article

Inflammatory Bowel Disease Medications

Sulfasalazine

Oligospermia has been reported with use of sulfasalazine as a treatment for inflammatory bowel disease.[43] It may also lower sperm motility and possibly decrease sperm normal morphology beginning 2 months after drug ingestion.[18,43] The exact mechanism is not known, but hormone levels including prolactin, LH, and FSH appear to be unaffected. Therefore, the most likely target is the testis and possibly the epididymis.[45,46] This is supported by recent animal studies that showed premature spermatid migration on histologic examination of rat testes post sulfasalazine administration.[45] These effects do not appear to be dose dependent.[47] Two to three months after discontinuation of the drug, semen parameters may improve though bowel disease may worsen.[18] Nonspermicidal alternatives to sulfasalazine exist, including mesalamine.

Azathioprine/6-mercaptopurine

Azathioprine has not been associated with erectile dysfunction or disruption of spermatogenesis.[47] A 2001 study by Dejaco et al showed no reduction in sperm quality in a cohort of 18 men taking this medication. In addition, during the period of the study, six men fathered children.[48] An animal study showed that treatment with 6-mercaptopurine (6-MP) did not affect sperm morphology or production when compared with controls, but noted an inverse correlation between pregnancy and 6-MP dose. They concluded that there is most likely occult sperm damage at the DNA level but not to basic semen quality.[49] Possibly consistent with this finding, a study by Rajapakse et al demonstrated a link between 6-MP taken by the fathers and an increased rate of congenital anomalies in naturally conceived offspring.[50] Similar findings were found in a Danish study, which also observed that all congenital anomalies in the exposed group were detected in male infants.[51] Thus, until larger studies are done, it is currently recommended that reproductive-age men consider banking sperm before initiating 6-MP therapy and use contraception while on therapy.

Tumor Necrosis Factor-alpha Blockers

Infliximab is a monoclonal antibody to tumor necrosis factor-alpha (TNF-α) that is frequently used to treat Crohn disease and ulcerative colitis. A prospective study demonstrated normal semen volume, concentration, and forward progression in patients on chronic doses of infliximab, but decreased normal sperm morphology by strict criteria.[52] In drug-naive patients beginning therapy, semen analyses revealed increased seminal volume, and a trend toward decreased sperm motility (p = 0.06).[52] More recently, a case study tied elevated TNF-α levels to male infertility, suggesting that more subtle alterations to semen quality may be present that are not reflected in the simple semen analysis with this drug.[53]

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