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Oral contraceptive use and mortality after 36 years of follow-up in the Nurses’ Health Study: prospective cohort study

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g6356 (Published 31 October 2014) Cite this as: BMJ 2014;349:g6356
  1. Brittany M Charlton, postdoctoral research fellow123,
  2. Janet W Rich-Edwards, associate professor145,
  3. Graham A Colditz, professor6,
  4. Stacey A Missmer, associate professor157,
  5. Bernard A Rosner, professor5,
  6. Susan E Hankinson, professor158,
  7. Frank E Speizer, professor59,
  8. Karin B Michels, associate professor1510
  1. 1Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
  2. 2Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital, Boston, MA, USA
  3. 3Department of Pediatrics, Harvard Medical School, Boston, MA, USA
  4. 4Connors Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
  5. 5Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  6. 6Department of Surgery, Washington University School of Medicine, St Louis, MO
  7. 7Division of Reproductive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  8. 8Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA
  9. 9Department of Environmental Health, Harvard School of Public Health, Boston, MA
  10. 10Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  1. Correspondence to: K B Michels kmichels{at}research.bwh.harvard.edu
  • Accepted 4 October 2014

Abstract

Objective To determine whether use of oral contraceptives is associated with all cause and cause specific mortality.

Design Prospective cohort study.

Setting Nurses’ Health Study, data collected between 1976 and 2012.

Population 121 701 participants were prospectively followed for 36 years; lifetime oral contraceptive use was recorded biennially from 1976 to 1982.

Main outcome measures Overall and cause specific mortality, assessed throughout follow-up until 2012. Cox proportional hazards models were used to calculate the relative risks of all cause and cause specific mortality associated with use of oral contraceptives.

Results In our population of 121 577 women with information on oral contraceptive use, 63 626 were never users (52%) and 57 951 were ever users (48%). After 3.6 million person years, we recorded 31 286 deaths. No association was observed between ever use of oral contraceptives and all cause mortality. However, violent or accidental deaths were more common among ever users (hazard ratio 1.20, 95% confidence interval 1.04 to 1.37). Longer duration of use was more strongly associated with certain causes of death, including premature mortality due to breast cancer (test for trend P<0.0001) and decreased mortality rates of ovarian cancer (P=0.002). Longer time since last use was also associated with certain outcomes, including a positive association with violent or accidental deaths (P=0.005).

Conclusions All cause mortality did not differ significantly between women who had ever used oral contraceptives and never users. Oral contraceptive use was associated with certain causes of death, including increased rates of violent or accidental death and deaths due to breast cancer, whereas deaths due to ovarian cancer were less common among women who used oral contraceptives. These results pertain to earlier oral contraceptive formulations with higher hormone doses rather than the now more commonly used third and fourth generation formulations with lower estrogen doses.

Footnotes

  • An abstract of this work was presented as an oral presentation at the annual meeting of the Society for Epidemiological Research on 28 June 2012. We thank the participants and staff of the Nurses’ Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY.

  • Contributors: All authors conceived and designed the study. JWR-E, GAC, SAM, BAR, SEH, FES, and KBM acquired the data. BMC analyzed the data and wrote the manuscript while all authors critically reviewed the manuscript and approved the final version. All authors also had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. The authors are not affiliated with the funding institutions. BMC and KBM act as the guarantors of the study.

  • Funding: The Nurses’ Health Study was supported by research grants P01CA87969, R01HL034594, and R01HL088521 of the National Institutes of Health. BMC was supported by the training grant T32HD060454 in reproductive, perinatal, and pediatric epidemiology from the National Institute of Child Health and Human Development, and the training program in cancer epidemiology under grant T32CA09001 from the National Cancer Institute, National Institutes of Health. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the institutional review board of the Brigham and Women’s Hospital in Boston, MA under protocol No 2010P001451. Informed consent was implied by the return of the baseline questionnaire.

  • Data sharing: Requests for access to data, statistical code, questionnaires, and technical processes may be made to the corresponding author at kmichels@research.bwh.harvard.edu.

  • Transparency: The lead author (BMC) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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