Oral Contraception May Not Increase Long-Term Mortality Rate
By Laurie Barclay, MD
Medscape Medical News
March 16, 2010 — Oral contraceptive use is not associated with increased long-term mortality rates, according to the results of a large, prospective UK cohort study reported in the March 11 issue of the BMJ.
"The Royal College of General Practitioners' (RCGP) Oral Contraception Study is one of the world's largest continuing investigations into the health effects of contraceptive pills," write Philip C. Hannaford, MD, from the University of Aberdeen, Foresterhill Health Centre, United Kingdom, and colleagues from the RCGP's Oral Contraception Study.
No Association Between Mortality and Oral Contraceptive Use
"Early reports from the study indicated an increased risk of death among ever users of these contraceptives, mainly because of an excess of vascular events among older users or those who smoked," the study authors write. "A later report, based on up to 25 years of follow-up, suggested that most of the mortality effects of oral contraceptives occurred in current or recent users, with few effects persisting beyond 10 years after stopping use."
The objective of the study was to see if the mortality risk among women who have used oral contraceptives differs from that of never-users. The cohort study began in 1968, with mortality data provided by participating general practitioners at 1400 general practices throughout the United Kingdom, National Health Service central registries, or both.
Participants were 46,112 women observed for up to 39 years, resulting in 378,006 woman-years of observation among never-users of oral contraception and 819,175 among ever-users. The main study endpoints were directly standardized adjusted relative risks for all-cause and cause-specific mortality between never-users and ever-users.
There were 1747 deaths in never-users of oral contraception and 2864 in ever-users. Ever-users of oral contraception had a significantly lower rate of all-cause mortality vs never-users (adjusted relative risk, 0.88; 95% confidence interval; 0.82 - 0.93). Rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynecologic cancers combined; all circulatory disease; ischemic heart disease; and all other diseases were also significantly lower in ever-users vs never-users. However, rates of violent deaths were higher in ever-users vs never-users.
Although there was no apparent association between overall mortality rate and duration of oral contraceptive use, some disease-specific associations were observed. Compared with never-users, women younger than 45 years who had stopped using oral contraceptives 5 to 9 years previously had an increased relative risk for death from any cause, but those with more distant use did not. Among ever-users of oral contraception, the estimated absolute reduction in all-cause mortality rate was 52 per 100,000 woman-years.
Strengths and Limitations of Study
When asked for independent comment by Medscape Ob/Gyn and Women's Health, Ward Cates, MD, MPH, president of research at Family Health International in Durham, North Carolina, noted various strengths and weaknesses of the study.
"[This was a] well done prospective cohort study of long-term complications from contraceptive choices; the exposure variable (contraceptive use) was regularly assessed; and the outcome variable (mortality) is an objective endpoint (indeed, the ultimate endpoint)," Dr. Cates said.
Study limitations noted by Dr. Cates were that exposures were not randomized, creating the potential for unmeasured selection and/or confounding; and previous articles from this database have acknowledged a relatively high rate of loss-to-follow-up (33%).
Do Results Apply to US Women?
Dr. Cates believes that the clinical implications of this study for US women are similar to those for UK women.
"Oral contraception was associated with a decreased long term risk of death in this large UK cohort," Dr. Cates told Medscape Ob/Gyn and Women's Health. "Thus providers can reassure women who have ever used oral contraceptives not only that they are not at increased [risk of] mortality from ever having used combined oral contraceptives but also that they may even have a net mortality benefit from their choice of contraception."
Regarding additional research, Dr. Cates recommended examining other long-term cohort studies of women using contraception to see if the findings are consistent with the findings from this UK study.
"Perceptions about the safety of oral contraception depend on whether current, recent, or more distant use of oral contraception is being assessed," the study authors conclude. "The balance of risks and benefits, however, may vary around the world, depending on patterns of oral contraception usage and the prevalence of different diseases."
The study received funding from the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Cruden Foundation, Schering AG, Schering Health Care, Wyeth Ayerst International, Ortho Cilag, and Searle. The Centre of Academic Primary Care has received payments from Schering-Plough and Wyeth Pharmaceutical for lectures and advisory board work provided by Dr. Hannaford. Dr. Cates is an author of the textbook Contraceptive Technology, now in its 19th edition, and has disclosed no other financial relationships.
