IPD from 45 studies were included: 13 prospective cohorts (7,726 cases and 32,201 controls) and 32 case-control studies (15,531 cases and 55,102 controls).
Women who had ever used oral contraceptives were significantly less likely to develop ovarian cancer than women who had never used oral contraceptives (RR 0.73, 95% confidence interval, CI: 0.70, 0.76, p<0.001). The longer they had used oral contraceptives, the lower their risk. The overall risk of ovarian cancer decreased by 20% (95% CI: 18, 23, p<0.0001) for each 5 years of use of oral contraceptives. This estimate was altered by less than 1% after adjusting for ethnicity, education, age at first birth, family history of breast cancer, age at menarche, menopausal status, use of hormone replacement therapy, height, weight, body mass index, use of alcohol or smoking, or all of these combined.
Reduced risk persisted but was attenuated over time. Proportional risk reductions per 5 years of use were 29% (95% CI: 23, 34) for use that had ceased less than 10 years previously, 19% (95% CI: 14, 24) for use that had ceased 10 to 19 years previously, and 15% (95% CI: 9, 21) for use that had ceased 20 to 29 years previously.
There was no evidence of a differential effect according to whether contraceptive use took place in the 1960s, 1970s or 1980s, even though the oestrogen dose had decreased substantially over time. Nor did the proportional risk reduction vary among different histological types (other than for mucinous tumours, for which incidence was little affected by oral contraceptive use).
The authors estimated that in high-income countries, 10 years’ use of oral contraceptives would reduce the risk of ovarian cancer before the age of 75 years from 1.2 per 100 users to 0.8 and mortality from 0.7 to 0.5, compared with never-users.
Data from three published studies were not available. The authors estimated that data from these studies would have increased the cases by only another 3%, that their results did not differ from those reported and, consequently, that inclusion would not have materially altered the overall findings of the review.