Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study

Abstract

Objective: To describe the long term effects of the use of oral contraceptives on mortality.

Design: Cohort study with 25 year follow up. Details of oral contraceptive use and of morbidity and mortality were reported six monthly by general practitioners. 75% of the original cohort was "flagged" on the NHS central registers.

Setting: 1400 general practices throughout Britain.

Subjects: 46 000 women, half of whom were using oral contraceptives at recruitment in 1968-9. Median age at end of follow up was 49 years.

Main outcome measures: Relative risks of death adjusted for age, parity, social class, and smoking.

Results: Over the 25 year follow up 1599 deaths were reported. Over the entire period of follow up the risk of death from all causes was similar in ever users and never users of oral contraceptives (relative risk=1.0, 95% confidence interval 0.9 to 1.1; P=0.7) and the risk of death for most specific causes did not differ significantly in the two groups. However, among current and recent (within 10 years) users the relative risk of death from ovarian cancer was 0.2 (0.1 to 0.8; P=0.01), from cervical cancer 2.5 (1.1 to 6.1; P=0.04), and from cerebrovascular disease 1.9 (1.2 to 3.1, P=0.009). By contrast, for women who had stopped use >/= 10 years previously there were no significant excesses or deficits either overall or for any specific cause of death.

Conclusion: Oral contraceptives seem to have their main effect on mortality while they are being used and in the 10 years after use ceases. Ten or more years after use ceases mortality in past users is similar to that in never users.

PIP: The Royal College of General Practitioners' oral contraception (OC) study was launched in 1968 to monitor the health of women who had used OCs. The results of the 25-year follow-up of a cohort of OC users are presented with regard to the effect of PC use upon mortality over the long term. Over 14 months from May 1968, 1400 general practitioners throughout the UK recruited to the study 23,000 women who were using OCs and a similar number who had never used them. The median age of study participants at the end of follow-up was 49 years. Over the follow-up period, 1599 deaths were reported. Over the entire period of follow-up, the risk of death from all causes was similar in ever users and never users of OCs, while the risk of death from most specific causes did not differ significantly in the 2 groups. However, among current users and those who had used OCs within the past 10 years, the relative risk of death from ovarian cancer was 0.2, 2.5 from cervical cancer, and 1.9 from cerebrovascular disease. The P-values for these relative risks are 0.01, 0.04, and 0.009, respectively. Among women who had stopped OC use at least 10 years ago, no significant excesses or deficits were observed either overall or for any specific cause of death. OCs therefore appear to have their main effect upon mortality while they are being used and in the 10 years after use is terminated.