Ovulation-inducing drugs and ovarian cancer risk: results from an extended follow-up of a large United States infertility cohort

ObjectiveTo examine the relationship of ovulation-inducing drugs and ovarian cancer.DesignRetrospective cohort study, with additional follow-up since initial report.SettingFive large reproductive endocrinology practices.Patient(s)In a retrospective cohort of 9,825 women evaluated for infertility at five clinical sites in the United States between 1965 and 1988 with follow-up through 2010, we examined the relationship of ovulation-inducing drugs and ovarian cancer (n = 85).Intervention(s)None.Main Outcome Measure(s)Hazard rate ratios (RR) and 95% confidence intervals (CI) for ovarian cancer.Result(s)Among women evaluated for infertility, there was no association of ovarian cancer risk with ever use of clomiphene citrate (CC) (adjusted RR 1.34, 95% CI 0.86–2.07) or gonadotropins (RR 1.00, 95% CI 0.48–2.08) and no evidence that any of several more detailed subgroups of usage were related to an increased risk with one exception: women who used CC and remained nulligravid did demonstrate much higher risks than those who successfully conceived compared with nonusers (respectively, RR 3.63, 95% CI 1.36–9.72 vs. RR 0.88, 95% CI 0.47–1.63).Conclusion(s)Our overall results were reassuring and consistent with other studies. A reason for an association between CC use and ovarian cancer among persistently nulligravid women remains to be determined. Given the large and increasing number of women treated with ovulation-inducing drugs, the increased risk of ovarian cancer among the subset of women who remained nulligravid should be further monitored.