Cancer risk after exposure to treatments for ovulation induction

Am J Epidemiol. 2009 Feb 1;169(3):365-75. doi: 10.1093/aje/kwn318. Epub 2008 Nov 26.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / etiology
  • Causality
  • Cohort Studies
  • Female
  • Humans
  • Incidence
  • Israel / epidemiology
  • Lymphoma, Non-Hodgkin / epidemiology*
  • Lymphoma, Non-Hodgkin / etiology
  • Melanoma / epidemiology*
  • Melanoma / etiology
  • Ovarian Neoplasms / epidemiology*
  • Ovarian Neoplasms / etiology
  • Ovulation Induction / adverse effects
  • Ovulation Induction / statistics & numerical data*
  • Proportional Hazards Models
  • Risk Assessment
  • Skin Neoplasms / epidemiology*
  • Skin Neoplasms / etiology
  • Uterine Neoplasms / epidemiology*
  • Uterine Neoplasms / etiology