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

doi:10.1136/bmj.g6356

Comparative Study

. 2014 Oct 31;349:g6356.

doi: 10.1136/bmj.g6356.

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

Brittany M Charlton¹, Janet W Rich-Edwards², Graham A Colditz³, Stacey A Missmer⁴, Bernard A Rosner⁵, Susan E Hankinson⁶, Frank E Speizer⁷, Karin B Michels⁸

Affiliations

¹ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, MA, USA Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³ Department of Surgery, Washington University School of Medicine, St Louis, MO.
⁴ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Division of Reproductive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Department of Environmental Health, Harvard School of Public Health, Boston, MA.
⁸ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA kmichels@research.bwh.harvard.edu.

PMID: 25361731
PMCID: PMC4216099
DOI: 10.1136/bmj.g6356

Free PMC article

Comparative Study

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

Brittany M Charlton et al. BMJ. 2014.

Free PMC article

. 2014 Oct 31;349:g6356.

doi: 10.1136/bmj.g6356.

Authors

Brittany M Charlton¹, Janet W Rich-Edwards², Graham A Colditz³, Stacey A Missmer⁴, Bernard A Rosner⁵, Susan E Hankinson⁶, Frank E Speizer⁷, Karin B Michels⁸

Affiliations

¹ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, MA, USA Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³ Department of Surgery, Washington University School of Medicine, St Louis, MO.
⁴ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Division of Reproductive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Department of Environmental Health, Harvard School of Public Health, Boston, MA.
⁸ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA kmichels@research.bwh.harvard.edu.

PMID: 25361731
PMCID: PMC4216099
DOI: 10.1136/bmj.g6356

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.

Conflict of interest statement

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.

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References

1. Cogliano V, Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F. Carcinogenicity of combined oestrogen-progestagen contraceptives and menopausal treatment. Lancet Oncol 2005;6:552-3. - PubMed
1. Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA 2000;284:72-8. - PubMed
1. Khader YS, Rice J, John L, Abueita O. Oral contraceptives use and the risk of myocardial infarction: a meta-analysis. Contraception 2003;68:11-7. - PubMed
1. Beral V, Doll R, Hermon C, Peto R, Reeves G. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 2008;371:303-14. - PubMed
1. Bosetti C, Bravi F, Negri E, La Vecchia C. Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis. Hum Reprod Update 2009;15:489-98. - PubMed

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[1] Cogliano V, Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F. Carcinogenicity of combined oestrogen-progestagen contraceptives and menopausal treatment. Lancet Oncol 2005;6:552-3. - PubMed

[2] Cogliano V, Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F. Carcinogenicity of combined oestrogen-progestagen contraceptives and menopausal treatment. Lancet Oncol 2005;6:552-3. - PubMed

[3] Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA 2000;284:72-8. - PubMed

[4] Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA 2000;284:72-8. - PubMed

[5] Khader YS, Rice J, John L, Abueita O. Oral contraceptives use and the risk of myocardial infarction: a meta-analysis. Contraception 2003;68:11-7. - PubMed

[6] Khader YS, Rice J, John L, Abueita O. Oral contraceptives use and the risk of myocardial infarction: a meta-analysis. Contraception 2003;68:11-7. - PubMed

[7] Beral V, Doll R, Hermon C, Peto R, Reeves G. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 2008;371:303-14. - PubMed

[8] Beral V, Doll R, Hermon C, Peto R, Reeves G. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 2008;371:303-14. - PubMed

[9] Bosetti C, Bravi F, Negri E, La Vecchia C. Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis. Hum Reprod Update 2009;15:489-98. - PubMed

[10] Bosetti C, Bravi F, Negri E, La Vecchia C. Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis. Hum Reprod Update 2009;15:489-98. - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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Cited by 32 articles

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Abstract

Conflict of interest statement

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Cited by 32 articles

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