Timing of pregnancy and the risk of epithelial ovarian cancer.

Recent animal studies suggest that progestagen-induced apoptosis of transformed ovarian surface epithelial cells may underlie the observed protective effect of pregnancy on the risk of ovarian cancer. Assuming that increasing numbers of cells are transformed with advancing age, we postulated that the benefits of pregnancy would be greater for older than younger women and tested this hypothesis in a population-based case-control study. We conducted interviews with 620 parous women, ages 18-79 years, with histologically confirmed incident ovarian cancer and 723 parous controls of the same age. Detailed information was collected on reproductive history, as well as hormonal exposures, smoking, medical history, and other factors. We estimated the relative risk of ovarian cancer associated with births at different ages through multiple logistic regression models. After adjusting for parity, older age at first and last births, and shorter time since last birth were all associated with significantly reduced risks of ovarian cancer. Age at first birth and time since last birth were not associated with ovarian cancer when adjusted for each other, whereas age at last birth remained strongly protective [odds ratio (OR), 0.57; 95% confidence interval (CI), 0.36-0.90] among women >35 years versus women less than 25 years. The effect was independent of total parity (per year of age among women with one birth: OR, 0.93; 95%CI, 0.87-1.01; among women with four or more births: OR, 0.96; 95%CI, 0.90-1.02). Our finding that ovarian cancer risk is reduced by pregnancy at older ages is further evidence that pregnancy confers a benefit beyond anovulation and is consistent with the theory that ovarian surface epithelial cell apoptosis induced by pregnancy hormones may be the underlying protective mechanism.