Sulphasalazine and male infertility: reversibility and possible mechanism.

Abstract

SUMMARY Earlier observations on infertility related to sulphasalazine treatment were extended and semen samples obtained from 28 patients with inflammatory bowel disease on treatment with sulphasalazine at 2-4g per day. Semen was examined for changes in density, motility, and morphology before, during, and after withdrawal of sulphasalazine. Gross semen abnormalities were seen in 18 patients on this drug for more than two months. Semen quality improved after sulphasalazine had been withdrawn for more than two months and 10 pregnancies are reported after sulphasazaine withdrawal. Preliminary endo-rine and acetylator phenotype studies do not elucidate the mechanism of this important new side-effect of this drug. The time course of the drug's effect on semen quality is consistent with the hypothesis that sulphasalazine or a metabolite, possibly sulphapyridine, is directly toxic to developing spermatozoa. These studies confirmed the preliminary report and suggest that prolonged treatment with sulphasalazine may universally depress semen quality and cause reversible infertility.Levi et al.1 gave details of four patients with sulphasalazine-associated infertility. Other reports have appeared in the literature.2-5 The aim of this study was to accumulate additional data on the nature and reversibility of semen abnormalities associated with sul,phasalazine and to elucidate the mechanism involved. Methods CLINICAL STUDYTwenty-eight male patients (age range 22-49 years) with histological and/or radiological documentation of inflammatory bowel disease, either ulcerative colitis or regional enteritis, were able to provide semen samples for the study. Consent was obtained from all patients. Semen was collected in a standardised way by masturbation into a sterile plastic container after at least 48 hours abstinence from seminal emission. Samples were kept at room temperature and analysed after liquefaction for (1) sperm dens,ity (normal range greater than or equal to 40X10') sperm/ml); (2) sperm motility (normal range greater than or equal to 60% progressively motile); (3) sperm morphology (normal range less than or equal to 30% abnormal forms). All samples were analysed

Management of inflammatory bowel disease in pregnancy

“…These findings are dose related and do not improve with supplemental folate [24]. Semen quality returned to normal 2-3 months after discontinuing sulfasalazine [25]. Therefore, it is advised that men with IBD on sulfasalazine considering conception should be switched to another oral mesalamine agent.…”

Inflammatory bowel disease in subfertile men and the effect of mesalazine on fertility

“…Sulphapyridine appears to cause oligozoospermia and has adverse effects on both sperm morphology and motility, but these effects are fully reversible upon drug cessation. Subsequent studies have consistently found not only improvements in sperm count, motility, and morphology but also successful conception after a switch to a different 5-ASA compound without the sulphapyridine component [Chatzinoff et al 1988;Cosentino et al 1984;O'Morain et al 1984;Riley et al 1987;Toovey et al 1981;Zelissen et al 1988]. However, a case of mesalazine-induced oligozoospermia in a young male with UC has been reported in Israel.…”

“…Past research showed that sulphasalazine causes oligozoospermia and has adverse effects on sperm morphology and motility [Cosentino et al 1984;Levi et al 1979;O'Morain et al 1984;Toovey et al 1981]. These effects are reversible, and semen quality can be restored after replacing sulphasalazine with mesalazine [Chatzinoff et al 1988;Riley et al 1987;Zelissen et al 1988].…”

Significance of Poisson distribution theory in analysing the interaction between human spermatozoa and zona-free hamster oocytes

“…As a result, Poisson analysis should find application in a variety of clinical conditions associated with asthenozoospermia, such as oligozoospermia or varicocoele, in permitting analysis of the penetrating ability of the spermatozoa in isolation from the defects in motility. Similarly, such analyses will permit a more effective interpretation of in-vitro fertilization data obtained after treatments which disrupt sperm motility, including cryostorage, ingestion of potential contraceptive agents such as gossypol (Aitken et al, 1983a) and sulphasalazine (Toovey, Hudson, Hendry & Levi, 1981), or in-vitro exposure to pharmacological reagents such as calmodulin inhibitors and adrenergic antagonists.…”