Reproductive and Hormonal Factors in Relation to Ovarian Cancer Risk and Survival

Abstract

Ovarian cancer etiology is not fully elucidated and few modifiable risk factors have been identified. Ovarian cancer treatment has changed over time; however, survival is still poor. I investigated reproductive and hormonal factors in relation to ovarian cancer risk and survival. In the Nurses’ Health Study (NHS), NHSII and New England Case-Control Study (NECC), I evaluated reproductive and hormonal factors and incidence of ovarian cancer characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status using polytomous logistic regression. In the NHSII, I investigated oral contraceptive (OC) use and ovarian cancer risk using Cox proportional hazards models. In the NECC, I evaluated the association of pre-diagnostic reproductive and hormonal factors with overall survival and platinum resistance among ovarian cancer cases using Cox proportional hazards models. Postmenopausal status was associated with an increased risk of PR- tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity=0.01) and age at natural menopause was inversely associated with PR- tumors (OR, per 5yr: 0.77; 95%CI: 0.61-0.96; p-het=0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het=0.0009). In OC analyses, OC use of <6 months was associated with an increased risk of ovarian cancer (HR: 1.53; 95%CI: 1.00-2.35) and a suggestion of a decreased risk with >10 years of OC use (HR: 0.84; 95%CI: 0.51-1.39) compared to never use. The increased risk appeared to be driven by duration of mestranol use. In survival analyses, self-reported endometriosis was associated with a 29% (95%CI: 0.54-0.94) decreased risk of total death. Additionally, longer duration of hormone therapy (HT) was associated with a decreased risk of death (HR, ≥5yr vs. never: 0.70; 95%CI: 0.54-0.89). Further >5 years of HT use was associated with a decreased risk of platinum resistance. While our results need to be confirmed in other studies, they suggest that the development of ovarian tumors through hormonal pathways differs by menopausal status, the association between OC use and ovarian cancer differs between younger and older birth cohorts, and that various reproductive and hormonal factors are associated with ovarian cancer survival. These results may help in further understanding ovarian cancer etiology and providing recommendations for ovarian cancer prevention and survival.