Cancer risk after exposure to treatments for ovulation induction

R. Calderon-Margalit*, Y. Friedlander, R. Yanetz, K. Kleinhaus, M. C. Perrin, O. Manor, S. Harlap, O. Paltiel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations


Uncertainty continues as to whether treatments for ovulation induction are associated with increased risk of cancer. The authors conducted a long-term population-based historical cohort study of parous women. A total of 15,030 women in the Jerusalem Perinatal Study who gave birth in 1974-1976 participated in a postpartum survey. Cancer incidence through 2004 was analyzed using Cox's proportional hazards models, controlling for age and other covariates. Women who used drugs to induce ovulation (n = 567) had increased risks of cancer at any site (multivariate hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.74). An increased risk of uterine cancer was found among women treated with ovulation-inducing agents (HR = 3.39, 95% CI: 1.28, 8.97), specifically clomiphene (HR = 4.56, 95% CI: 1.56, 13.34). No association was noted between use of ovulation-inducing agents and ovarian cancer (age-adjusted HR = 0.61, 95% CI: 0.08, 4.42). Ovulation induction was associated with a borderline- significant increased risk of breast cancer (multivariate HR = 1.42, 95% CI: 0.99, 2.05). Increased risks were also observed for malignant melanoma and non-Hodgkin lymphoma. These associations appeared stronger among women who waited more than 1 year to conceive. Additional follow-up studies assessing these associations by drug type, dosage, and duration are needed.

Original languageAmerican English
Pages (from-to)365-375
Number of pages11
JournalAmerican Journal of Epidemiology
Issue number3
StatePublished - Feb 2009


  • Breast neoplasms
  • Cohort studies
  • Incidence
  • Lymphoma, non-Hodgkin
  • Melanoma
  • Ovarian neoplasms
  • Ovulation induction
  • Uterine neoplasms


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