Background: Parity and use of oral contraceptive (OC) are associated with reduced risk of ovarian cancer. However, it is not clear whether these exposures have similar risk effects during different periods of life. In a large consortial analysis, we seek to evaluate the risk reductions associated with pregnancy and with OC use in different periods during the lifetime of a woman.

Methods: We combined data from 17 population-based case-control studies of ovarian cancer that are part of the Ovarian Cancer Association Consortium (OCAC). Odds ratios (ORs) and 95% confidence intervals (CI) for associations between age of pregnancies and duration of OC use were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Analyses were adjusted for age, duration of OC use, number of pregnancies, and race (Caucasian, Black, Asian and other). Studies that matched on ethnicity were additionally adjusted for Hispanic ethnicity (yes/no). All tests were two-sided and P-values less than 0.05 were considered statistically significant.

Results: The analysis included 15,033 ovarian cancer cases and 25,312 controls. The median age for cases was 57 (interquantile range: 50-65) and 56 for controls (interquantile range: 48-64). Approximately 83.4% of cases and 88.5% of controls reported at least one pregnancy and 55.4% of cases and 61.7% of controls reported OCs use for at least one month. On average, each pregnancy was associated with a 17% reduced risk of ovarian cancer (OR=0.83, 95% CI: 0.8-0.85) while each year of OC use was associated with a 6% reduced risk (OR=0.94, CI 0.92-0.95). Among women who reported having at least one pregnancy, older age at last pregnancy was associated with lower risk of ovarian cancer (P<0.0001). Specifically, compared to women whose last pregnancy was before the age of 25, women who had their last pregnancy between the ages of 25-30 had a 15% reduced risk of ovarian cancer (OR=0.85, 95% CI: 0.78-0.93), women who had their last pregnancy between the ages of 30-35 had a 18% reduced risk of ovarian cancer (OR=0.82, 95% CI: 0.74-0.90) and women who had their last pregnancy after the age of 35 had a 21% reduced risk of ovarian cancer (OR=0.79, 95% CI: 0.70-0.90). Similar findings were observed when analyses were stratified by increasing number of pregnancies. With respect to OC use, compared to women who reported the age at last used before the age of 25, those who reported the age at last use to be between the ages of 25-30 had a 15% lower risk of ovarian cancer (OR=0.85, 95% CI: 0.73-0.98) and those who reported the age of last use was after the age of 30 had a 18% reduced risk of ovarian cancer (OR=0.82, 95% CI: 0.66-1.03 for age at last used between 30-35; OR=0.82, 95% CI: 0.63-1.07 for age at last older than 35), but the trend was not significant.

Conclusions: In summary, older age at last pregnancy was significantly associated with reduced risk of ovarian cancer. There was a suggestion that older age at last used of OCs was associated with lower risk of ovarian cancer. These findings suggest that use of OCs to later ages in life can reduce ovarian cancer risk. A joint evaluation of life periods with pregnancies and OC use and ovarian cancer risk is under way.

Citation Format: Clara Bodelon, Harvey Risch, Francesmary Modugno, Penelope Webb, Celeste Leigh Pearce, Malcolm Pike, Nicolas Wentzensen. Timing of pregnancies and oral contraceptive use and risk of ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A27.