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

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 > or =6 cycles, RR = 1.96, 95% CI: 1.03, 3.72) and human chorionic gonadotropin (for > or =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.