Abstract A95: The impact of fertility drug use, infertility, and lifetime ovulation on ovarian cancer risk

Abstract

Abstract Background: Ovarian cancer (OC) risk is associated with factors related to lifetime ovulation including hormone use, pregnancy, and breastfeeding. Factors increasing lifetime ovulation have been found to be positively associated with OC risk. Concern regarding the use of fertility drugs, the majority of which stimulate ovulation, and OC risk has increased over the past several decades as the rate of women seeking fertility treatment rapidly rises. The relationship between fertility drug use and OC is complex because the association may be attributable to several factors including: greater number of lifetime ovulatory cycles among nulliparous women, underlying causes of infertility, shared genetic susceptibility to ovarian cancer and infertility, or a correlate of infertility such as the use of fertility drugs. Controversy has surrounded fertility drug use as it relates to OC risk due to inconclusive results from previous studies, which were unable to account for these factors. Objective: The objective of this study was to evaluate the relationship between fertility drug use and OC risk, distinguish the effect of fertility drugs from underlying causes of infertility, and determine whether the relationship is modified by lifetime ovulation. Methods: The Hormones and Ovarian Cancer Prediction (HOPE) study includes 902 ovarian/peritoneal/fallopian tube cancer cases and 1,802 population-based controls recruited from Pennsylvania, Ohio, and New York and enrolled between 2003 and 2008. Trained interviewers collected detailed reproductive and medical histories through in-person interviews. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for fertility drug use and OC risk. Fertility drug use was classified as either never or ever using fertility drugs. The models were adjusted for age, race, education, site, family history of ovarian and breast cancers, duration of oral contraceptive use, duration of breastfeeding, hormone replacement therapy, tubal ligation, parity, and talc use. Lifetime ovulatory years were estimated by subtracting age of menarche from age of menopause and adjusting this by time spent pregnant, breastfeeding, or taking ovulation-suppressing contraceptives. Lifetime ovulation was classified as low, intermediate and high based on tertiles within age groups (<35, 35–55, and ≥55). Breslow-Day tests of homogeneity were used to assess the relationship between fertility drug use and OC risk with lifetime ovulation stratified by age as well as underlying causes of infertility. Results: Fertility drug use was not significantly associated with OC risk [OR=1.02, 95% CI: 0.70–1.47] when adjusting for known OC risk factors; the relationship remained non-significant when accounting for duration of use [OR=1.00, 95% CI: 0.98–1.01], and cause of infertility [p-heterogeneity=0.85]. Fertility drug use also remained non-significant after stratifying by lifetime ovulatory years for women <35 years old [p-heterogeneity=0.86], women 35–55 years old [p-heterogeneity=0.78], and women ≥55 years old [p-heterogeneity=0.52]. Lifetime ovulatory years were independently associated with OC risk among women <35 [OR=1.13, 95% CI: 1.04–1.23] and women 35–55 years old [OR=1.06, 95% CI: 1.04–1.08], but not for women ≥55 [OR=1.01, 95% CI: 0.99–1.02. Conclusion: These results provide further evidence that fertility drug use does not significantly contribute to overall OC risk when controlling for known risk factors and underlying cause of infertility. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A95.