BACKGROUND:Oralcontraceptive (OC) use is associated with a reducedriskof developingovarian cancer, but the mechanism for theriskreduction has not been well defined. In this study, we investigate the relationship between theprogestinandestrogenpotencyin combination OCs and theriskof developingovarian cancer.METHODS:The study included 390 case subjects with epithelialovarian cancerand 2865 control subjects, between 20 and 54 years of age, identified from theCancerand Steroid Hormone Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations betweenovarian cancerriskand combination OC formulations while controlling for potential confounders. All statistical tests were two-sided.RESULTS:With users of high-progestin/high-estrogenpotencyOC as the referent group, users of low-progestin/high-estrogenpotencyformulations (adjusted OR = 2.1; 95% CI = 1.2 to 3.7) and low-progestin/low-estrogenpotencyformulations (adjusted OR = 1.6; 95% CI = 0.9 to 3.0) had a higherriskofovarian cancerthan users of high-progestin/high-estrogenpotencyformulation. Low-progestinpotencyOC formulations were associated with a statistically significant higherriskthan high-progestinpotencyformulations (adjusted OR = 2.2; 95% CI = 1.3 to 3.9). This association was seen even among users of short duration.CONCLUSION:The combination OC formulations with high-progestinpotencyappear to be associated with a greater reduction inovarian cancerriskthan those with low-progestinpotency. Mechanisms underlying this reduction may include inhibition of ovulation and/or some direct biologic effects of theprogestin.