BMJ 1999;318:96-100 ( 9 January )

General Practice

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

Editorial by Skegg

Valerie Beral, professor, a Carol Hermon, scientific officer, a Clifford Kay, director, b Philip Hannaford, professor, b Sarah Darby, professor, a Gillian Reeves, statistician. a

a Imperial Cancer Research Fund, Cancer Epidemiology Unit, Radcliffe Infirmary, Oxford OX2 6HE, b Royal College of General Practitioners, Manchester Research Unit, Parkway House, Manchester M22 4DB

Correspondence to: Professor Beral beral{at}icrf.icnet.uk

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.

Key messages

  • This 25 year follow up of 46 000 UK women found a decrease in mortality from ovarian cancer and an increase in mortality from circulatory diseases and cervical cancer among women were using oral contraceptives or had used them in the past 10 years

  • 10 or more years after stopping use mortality was similar in past users and never users

  • Oral contraceptives seem to have their main effect on mortality mainly while they are being used and in the 10 years after stopping use

  • There is little evidence to suggest any persistent adverse effect 10 or more years after use of oral contraceptives ceases




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