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American Journal of Epidemiology Advance Access published online on November 1, 2009
American Journal of Epidemiology, doi:10.1093/aje/kwp290
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American Journal of Epidemiology © The Author 2009. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Original Contribution

Use of Fertility Drugs and Risk of Uterine Cancer: Results From a Large Danish Population-based Cohort Study

Allan Jensen*, Heidi Sharif and Susanne K. Kjaer

* Correspondence to Dr. Allan Jensen, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen N, Denmark (e-mail: allan{at}cancer.dk).

Received for publication April 7, 2009. Accepted for publication August 13, 2009.

Some epidemiologic studies have indicated that uterine cancer risk may be increased after use of fertility drugs. To further assess this association, the authors used data from a large cohort of 54,362 women diagnosed with infertility who were referred to Danish fertility clinics between 1965 and 1998. In a case-cohort study, rate ratios and 95% confidence intervals were used to assess the effects of 4 groups of fertility drugs on overall risk of uterine cancer after adjustment for potentially confounding factors. Through mid-2006, 83 uterine cancers were identified. Ever use of any fertility drug was not associated with uterine cancer risk (rate ratio (RR) = 1.10, 95% confidence interval (CI): 0.69, 1.76). However, ever use of gonadotropins (follicle-stimulating hormone and human menopausal gonadotropin) increased uterine cancer risk (RR = 2.21, 95% CI: 1.08, 4.50); the risk was primarily observed after 10 years of follow-up. Furthermore, uterine cancer risk increased with number of cycles of use for clomiphene (for ≥6 cycles, RR = 1.96, 95% CI: 1.03, 3.72) and human chorionic gonadotropin (for ≥6 cycles, RR = 2.18, 95% CI: 1.16, 4.08) but not for other gonadotropins. Use of gonadotropin-releasing hormone analogs was not associated with risk. Gonadotropins, and possibly clomiphene and human chorionic gonadotropin, may increase the risk of uterine cancer, with higher doses and longer follow-up leading to greater risk.

clomiphene; cohort studies; Denmark; fertility agents; gonadotropins; infertility; uterine neoplasms

Abbreviations: CI, confidence interval; GnRH, gonadotropin-releasing hormone; hCG, human chorionic gonadotropin; RR, rate ratio


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