Inflammatory Bowel Disease Medications
Oligospermia has been reported with use of sulfasalazine as a treatment for inflammatory bowel disease. 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. These effects do not appear to be dose dependent. Two to three months after discontinuation of the drug, semen parameters may improve though bowel disease may worsen. Nonspermicidal alternatives to sulfasalazine exist, including mesalamine.
Azathioprine has not been associated with erectile dysfunction or disruption of spermatogenesis. 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. 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. 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. Similar findings were found in a Danish study, which also observed that all congenital anomalies in the exposed group were detected in male infants. 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. In drug-naive patients beginning therapy, semen analyses revealed increased seminal volume, and a trend toward decreased sperm motility (p = 0.06). 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.
Semin Reprod Med. 2013;31(4):286-292. © 2013 Thieme Medical Publishers