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

Objective: To examine the relationship of ovulation-inducing drugs and ovarian cancer. Design: Retrospective cohort study, with additional follow-up since initial report. Setting: Five 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. (Fertil Steril (R) 2013;100:1660-6. (C)2013 by American Society for Reproductive Medicine.)