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

https://doi.org/10.1016/j.ajog.2017.02.002Get rights and content

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 that are associated with oral contraception. Despite previous research, important questions remain about the safety of these contraceptives: (1) How long do endometrial, ovarian, and colorectal cancer benefits persist? (2) Does combined oral contraceptive use during the reproductive years produce new cancer risks later in life? (3) What is the overall balance of cancer among past users as they enter the later stages of their lives?

Objectives

The purpose of this study was to examine the very long-term cancer risks or benefits associated with the use of combined oral contraceptives, including the estimated overall life-time balance.

Study Design

The 46,022 women who were recruited to the UK Royal College of General Practitioners’ Oral Contraception Study in 1968 and 1969 were observed for up to 44 years. Directly standardized rates of specific and any cancer were calculated for “ever” and “never” users of combined oral contraceptives; data were standardized for age, parity, social class, and smoking. Attributable risk and preventive fraction percentages were calculated. Poisson regression that adjusted for the same variables was used to estimate incidence rate ratios between ever and never users and to examine effects by time since last oral contraceptive use.

Results

There were 4661 ever users with at least 1 cancer during 884,895 woman-years of observation and 2341 never users with at least 1 cancer during 388,505 woman-years of observation. Ever use of oral contraceptives was associated with reduced colorectal (incidence rate ratio, 0.81; 99% confidence interval, 0.66–0.99), endometrial (incidence rate ratio, 0.66; 99% confidence interval, 0.48–0.89), ovarian (incidence rate ratio, 0.67; 99% confidence interval, 0.50–0.89), and lymphatic and hematopoietic cancer (incidence rate ratio, 0.74; 99% confidence interval, 0.58–0.94). An increased risk of lung cancer was seen only among ever users who smoked at recruitment. An increased risk of breast and cervical cancer that was seen in current and recent users appeared to be lost within approximately 5 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.

Conclusion

Most women who choose to use oral contraceptives do not expose themselves to long-term cancer harms; instead, with some cancers, many women benefit from important reductions of risk that persist for many years after stopping.

Section snippets

Materials and Methods

Between May 1968 and July 1969, 1400 general practitioners (GPs) throughout the United Kingdom recruited approximately 23,000 women who were using oral contraceptives and 23,000 women who had never used this method of contraception.5 All women were married or co-habiting; most were white, and their mean age at recruitment was 29 years. Information collected at recruitment included previous use of oral contraception, smoking habits, social class (based on partner’s occupation according to the

Results

The dataset contained 4661 ever users with at least 1 cancer during 884,895 woman-years of observation and 2341 never users with at least 1 cancer during 388,505 woman-years of observation, which was an 81% increase in cancers and an 18% increase in periods of observation since our previous cancer analysis.8 Approximately one-tenth of never users who experienced cancer (246 women; 10.5%) and a similar proportion of ever users (458 women; 9.8%) had >1 type of cancer. The mean age of women at

Comment

Our results suggest that users of oral contraceptives are protected from colorectal, endometrial, and ovarian cancer for many years after stopping, perhaps for >35 years for colorectal and ovarian cancer. An increased breast and cervical cancer risk that is seen in current and recent users appears to be lost within approximately 5 years of stopping oral contraception, with no evidence of either cancer recurring at increased risk in ever users with time. An increased risk of lung cancer was seen

Acknowledgments

We thank many general practitioners who contributed data, the University of Aberdeen Data Management Team for database support, and Dr Gordon Prescott for assistance with the time since last use analyses.

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    Supported by the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care Ltd, Wyeth Ayerst International, Ortho Cilag and, Searle. None of these funders have contributed to the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.

    The authors report no conflict of interest.

    Cite this article as: Iversen L, Sivasubramaniam S, Lee AJ, et al. Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study. Am J Obstet Gynecol 2017;216:580.e1-9.

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