Oral Contraceptives and the Risk of Endometrial Cancer

Summary

A meta-analysis 1 included 36 studies with 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls). The longer women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0.76 (95% CI 0.73 to 0.78; p<0.0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0.69, 95% CI 0.66 to 0.71) than sarcomas (RR 0.83, 95% CI 0.67 to 1.04; case-case comparison: p=0.02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2.3 to 1.3 per 100 women.

The 46 022 women in the UK Royal College of General Practitioners' Oral Contraception Study 2 were observed for up to 44 years to assess very long-term cancer risks or benefits associated with the use of combined oral contraceptives. There were 4661 ever users with at least 1 cancer during 884 895 woman-years of observation and 2341 never users with at least 1 cancer during 388 505 woman-years of observation. Ever use of oral contraceptives was associated with reduced colorectal (incidence rate ratio, 0.81, 99% CI 0.66 to 0.99), endometrial (incidence rate ratio, 0.66, 99% CI 0.48 to 0.89), and ovarian cancer (incidence rate ratio, 0.67, 99% CI 0.50 to 0.89).

An observational study 3 involving a total of 256 661 women from UK Biobank, born between 1939 and 1970 evaluated the long-term oral contraceptive use and cancer risk. The odds were lower among ever users, compared with never users, for ovarian cancer (OR 0.72, 95% CI 0.65 to 0.81) and endometrial cancer (OR 0.68, 95% CI 0.62 to 0.75), an association that was stronger with longer use (P < 0.001). The protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives.