American Journal of Epidemiology Advance Access published online on November 26, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn318
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Original Contribution |
Cancer Risk After Exposure to Treatments for Ovulation Induction
Correspondence to Dr. Ronit Calderon-Margalit, Braun School of Public Health and Community Medicine, Hadassah-Hebrew University, P.O. Box 12272, 91120 Jerusalem, Israel (e-mail: ronitc{at}ekmd.huji.ac.il).
Received for publication January 23, 2008. Accepted for publication September 11, 2008.
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.
breast neoplasms; cohort studies; incidence; lymphoma, non-Hodgkin; melanoma; ovarian neoplasms; ovulation induction; uterine neoplasms
Abbreviations: CI, confidence interval; HR, hazard ratio; ICDO-3, International Classification of Diseases for Oncology, Third Edition
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