Azathioprine treatment and male fertility in inflammatory bowel disease

Gastroenterology. 2001 Nov;121(5):1048-53. doi: 10.1053/gast.2001.28692.


Background & aims: Long-term treatment with azathioprine (AZA) is well established in inflammatory bowel disease (IBD). AZA is metabolized to 6-mercaptopurine (6-MP), which interacts in purine metabolism and is therefore considered to have mutagenic potentials. This is the first study to examine the influence of AZA on semen quality.

Methods: Semen quality was examined and compared with World Health Organization (WHO) standards regarding sperm density, motility, morphology, ejaculate volume, and total sperm count in 23 IBD patients treated with AZA. In 10 of these patients, a semen sample was assessed before and during AZA treatment; in another 5, semen analysis was performed twice during at least 2 years of AZA therapy.

Results: In 18 patients treated with 1.5-2 mg/kg AZA daily for at least 3 months but without sulfasalazine, sperm density was 94 +/- 84 Mio/mL (94% within WHO standard), motility was 60% +/- 20% (67% within WHO standard), the proportion of sperm with normal morphology was 44% +/- 21% (67% within WHO standard), ejaculate volume was 3.4 +/- 1.5 mL (89% within WHO standard), and total sperm count was 297 +/- 272 Mio (94% within WHO standard). No changes in semen parameters were noted after 11 +/- 5 months of AZA administration or during long-term treatment (49 +/- 14 months). Sulfasalazine administration in 5 patients was associated with markedly reduced semen morphology. During the study period, 6 patients fathered 7 healthy children.

Conclusions: Our data show that AZA does not reduce semen quality and thereby male fertility in IBD.

MeSH terms

  • Adolescent
  • Adult
  • Azathioprine / adverse effects*
  • Fertility / drug effects*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Inflammatory Bowel Diseases / drug therapy*
  • Leukocyte Count
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Semen / drug effects*


  • Immunosuppressive Agents
  • Azathioprine