A meta-analysis included 45 epidemiological studies in 21 countries involving 23 257 women with ovarian cancer (cases) and 87 303 controls. Overall 7 308 (31%) cases and 32 717 (37%) controls had ever used oral contraceptives, for average durations among users of 4.4 and 5.0 years, respectively. For ever vs. never users the overall relative risk was 0.73 (95% CI 0.70 to 0.76). The longer the use of oral contraceptives, the greater the reduction in ovarian cancer risk (p<0.0001). The overall relative risk decreased by 20 % (95% CI 18 to 23%) for each year of use. This reduction attenuated somewhat over time: the 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% (14–24%) for use that had ceased 10–19 years previously, and 15% (9–21%) for use that had ceased 20–29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The proportional risk reduction did not vary much between different histological types (except of mucinous tumours which seemed little affected by oral contraceptives). In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100; for every 5 000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented.
In a UK cohort study the main dataset contained about 339 000 woman years of observation for never users and 744 000 woman years for ever users of oral contraception. Compared with never users ever users had statistically significant lower rates of cancers of ovaries (RR 0.54, 95% CI 0.40 to 0.71), large bowel or rectum, uterine body, main gynaecological cancers combined, and any cancer. Statistically significant trends of increasing risk of cervical and central nervous system or pituitary cancer, and decreasing risk of uterine body and ovarian malignancies were seen with increasing duration of oral contraceptive use.
Comment: The quality of evidence is upgraded by time-response gradient.