Oral contraceptive use decreases the risk of ovarian cancer, but no previous studies have assessed the impact of cumulative intake of estrogen and progestin on ovarian cancer risk.

We used data from a population-based case–control study conducted in Denmark in 1995–1999 among women aged 35–79 years; 554 women with epithelial ovarian cancer and 1,564 age-matched controls were included in the analyses. Data were analyzed in multiple logistic regression models.

The use of combined oral contraceptives only and the mixed use of combined and progestin-only pills decreased the risk of ovarian cancer, while no association was found with exclusive use of progestin-only pills. No major differences in risk were found for users of combined oral contraceptives with high- and low-potency estrogen and progestin. There was no effect of cumulative progestin intake, but decreased risks of ovarian cancer with increasing cumulative intake of estrogen (OR = 0.82; 95 % CI 0.67–0.99, per 100 mg estrogen) and increasing duration of oral contraceptive use (OR = 0.95; 95 % CI 0.92–0.98, per year of use) were found. No effect of cumulative estrogen intake was found, however, after adjustment for duration of oral contraceptive use.

The protective effect of oral contraceptives against ovarian cancer may be sufficiently explained by duration of anovulation. This suggests that if the estrogen and progestin doses are sufficient to cause anovulation, a higher intake of estrogen or progestin confers no extra protection against ovarian cancer.