The aims of the present study are to further examine the complex associations between childbearing and ovarian cancer risk. We will evaluate the hypothesis that pregnancy-dependent clearance effect reduces ovarian cancer risk by examining whether the protective effect of childbearing diminishes over time. We will examine indirectly whether exposure to progesterone contributes to the protective effect of childbearing by evaluating the effect of twinning (dizygotic twins in particular) and birth spacing. We will utilize a linked database from Swedish nation-wide registries (the Fertility Register, the Cancer Register, and the Twin Register). Members of the study cohort are all women who were born from 1925 and on and listed in the Fertility Register. We adopt a nested case-control sampling design to allow more efficient analyses. Case subjects are more than 9,000 cohort members diagnosed with invasive ovarian cancer tumors from 1961 to 1999 as identified by the Cancer Register. Control subjects are approximately 45,000 women randomly selected from the Fertility Register and matched by birth year with the index cases. We will model the data through conditional logistic regression to estimate odds ratios associated with reproductive study characteristics. Further analyses will examine the effect of age at last birth in different age groups and assess postpartum time-dependent ovarian cancer risk. This study seeks to further our understanding of the mechanisms behind the protective effect of childbearing utilizing the uniquely large database, the ability to determine the zygosity of twins, the analyses within specific age groups of women, and the known endocrine physiology associated with the study variables. Examination of the effect of delayed childbearing in younger women could provide further insight into the potential mechanism attributable to its putative protective effect against ovarian cancer occurrence, while examination of the effect of childbearing in older women can better document whether the pregnancy-dependent clearance effect diminishes with time. Improved understanding of the etiology and carcinogenic process of ovarian cancer could lead to the development of hormonal prevention methods that mimic relevant aspects of the protective effect of childbearing.