Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study

Background: Oral contraceptives have been used by hundreds of millions of women around the world. Important questions remain regarding the very long-term cancer risks associated with oral contraception. Despite previous research important questions remain about the safety of these contraceptives: i) how long do endometrial, ovarian and colorectal cancer benefits persist for? ii) does combined oral contraceptive use during the reproductive years produce new cancer risks later in life? and iii) what is the overall balance of cancer among past users as they enter the later stages of their lives?
Objectives: To examine the very long-term cancer risks or benefits associated with use of combined oral contraceptives, including the estimated overall life-time balance.
Study design: 46,022 women recruited to the UK Royal College of General Practitioners’ Oral Contraception Study during 1968/69 were followed-up for up to 44 years. Directly standardised rates of specific and any cancer were calculated for ever and never users of combined oral contraceptives; standardised for age, parity, social class and smoking. Attributable risk percentage and preventive fraction percentage were calculated. Poisson regression adjusting for the same variables was used to estimate incidence rate ratios (IRR) between ever and never users, and examine effects by time since last oral contraceptive use
Results: There were 4661 ever users with at least one cancer during 884,895 woman-years of observation and 2341 never users with at least one cancer during 388,505 woman-years of observation. Ever use of oral contraceptives was associated with reduced colorectal (IRR 0·81, 99% confidence interval, CI 0·66 to 0·99), endometrial (IRR 0·66, 99% CI 0·48 to 0·89), ovarian (IRR 0·67, 99% CI 0·50 to 0·89) and lymphatic and haematopoietic cancer (IRR 0·74, 99% CI 0·58 to 0·94). An increased risk of lung cancer was seen only among ever users who smoked at recruitment. An increased risk of breast and cervical cancer seen in current and recent users appeared to be lost within about five years of stopping oral contraception, with no evidence of either cancer recurring at increased risk in ever users with time. There was no evidence of new cancer risks appearing later in life among women who had used oral contraceptives. Thus, the overall balance of cancer risk among past users of oral contraceptives was neutral with the increased risks counterbalanced by the endometrial, ovarian and colorectal cancer benefits that persist at least 30 years.
Conclusions: Most women who choose to use oral contraceptives do not expose themselves to long-term cancer harms; instead many benefit from important reductions in some cancers which persist for many years after stopping.