Use of oral contraceptives is not associated with increased risk of death in the UK; a net benefit in all-cause mortality was seen in ever users versus never users – RR 0.88, 95% CI 0.82 to 0.93
- Correspondence to Jane Clarke
Faculty of Medical and Health Sciences, School of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand;
The combined oral contraceptive pill (OCP) was first used in 1956 in Puerto Rico and is frequently referred to as ‘the Pill’. It is a combination of oral oestrogen and a progestin (progestogen) taken for contraception by over 100 million women worldwide. The OCPs were perceived as a convenient, effective and reversible means of contraception. Ever since OCPs were first introduced, their relative safety has been the focus of much debate.1 Concerns are derived from the influences that these hormone-based therapies are used upon a series of adverse events including circulatory disease and cancer.2 Since the introduction of OCPs in the 1960s, sufficient time has now elapsed to allow investigators to complete an adequately powered cohort study to determine the RRs associated with the use of OCPs. The Royal College of General Practitioners' Oral Contraception Study is one of the largest studies considering the relative safety of OCPs.
The objective of the prospective cohort study was to establish the mortality risk among women who have used oral contraceptives differs from that of never users. The study commenced in 1968 with mortality data provided by general practitioners from 1400 practices in UK and/or National Health Service central registries. Observation of 46 112 women for up to 39 years, provided data on 378 006 woman-years among never users of oral contraception and 819 175 among ever users. The primary study outcomes were directly standardised adjusted RRs for all-cause and cause-specific mortality between these respective groups.
No association between mortality and oral contraceptive use
Initial findings from this study suggested an increased risk of death among ever users of contraceptives in particular with older users and/or smokers. Subsequent to this, the evidence gleaned from 25 years of additional follow-up indicated that occurrence of most of the mortality effects of oral contraceptives was with current or recent users with few effects seen beyond 10 years after discontinuation.
There were 1747 deaths in never users versus 2864 in ever users. No association between overall mortality and duration of oral contraceptive use was seen, some disease-specific associations were observed. Ever users of oral contraception had a significantly lower rate of all-cause mortality versus never users (adjusted RR 0.88, 95% CI 0.82 to 0.93). Among ever users, the estimated absolute reduction in all-cause mortality was 52 per 100 000 woman-years. Violent death rates were higher in ever users versus never users (adjusted RR 1.49, 95% CI 1.09 to 2.05).
Compared with never users, women younger than 45 years who had stopped using oral contraceptives 5–9 years previously had an increased RR for death from any cause, but those with more distant use did not.
Strengths and weaknesses of the study
The selection of study type was appropriate for the given study objectives. The methodology employed was robust. Adjustments were made for some confounders such as smoking but not for the two very influential lifestyle and familial confounders. Loss-to-follow-up (33%) was very high. The higher violent death rates seen in ever users suggest that the characteristics of individuals within the two groups were not similar. Over the study period, many radical changes have occurred including changes to the hormonal content of the OCP and prescribing practices, and none of these were adjusted for. The impact of this may be that the effect seen may be either a false positive or negative.
The international applicability of these results is debatable as the patterns of oral contraception usage and the prevalence of different diseases vary. As with all non-randomised studies, these findings must be viewed by stakeholders with caution.3