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.
Jensen
Allan
A
Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen N, Denmark. allan@cancer.dk
Sharif
Heidi
H
Kjaer
Susanne K
SK
D000328:Adult; D000368:Aged; D006063:Chorionic Gonadotropin / Q000009:adverse effects; D002996:Clomiphene / Q000009:adverse effects; D015331:Cohort Studies; D016001:Confidence Intervals; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects*; D006062:Gonadotropins / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D010298:Parity; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D055815:Young Adult
D006063:Chorionic Gonadotropin; D005300:Fertility Agents, Female; D006062:Gonadotropins; D002996:Clomiphene