Elsevier

The Lancet Oncology

Volume 16, Issue 9, September 2015, Pages 1061-1070
The Lancet Oncology

Articles
Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies

https://doi.org/10.1016/S1470-2045(15)00212-0Get rights and content

Summary

Background

Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors.

Methods

Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy.

Findings

The median age of cases was 63 years (IQR 57–68) and the median year of cancer diagnosis was 2001 (IQR 1994–2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1–7) and 4·4 years (IQR 2–9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73–0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66–0·71) than sarcomas (0·83, 0·67–1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women.

Interpretation

Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965–2014) by oral contraceptives, including 200 000 in the past decade (2005–14).

Funding

Medical Research Council, Cancer Research UK.

Introduction

Use of oral contraceptives is known to reduce the incidence of endometrial cancer.1 Because endometrial cancer is uncommon in young women but its incidence increases sharply with age, the public health effects of this inverse association depend mainly on the extent to which the reduced risk of endometrial cancer persists long after use ceases. To investigate the association between use of oral contraceptives and the subsequent risk of endometrial cancer, individual participant data from 36 epidemiological studies of endometrial cancer have been brought together and analysed centrally.

Section snippets

Identification of studies and collection of data

This collaboration was established in 2005. Since 2012, epidemiological studies were eligible for inclusion if they collected individual data about use of hormonal contraceptives and reproductive history from at least 400 women with endometrial cancer in retrospective studies, and at least 200 women in prospective studies. Before 2012, retrospective studies with fewer than 400 cases of endometrial cancer had been eligible, so some studies with fewer cases are included in this analysis. Eligible

Results

Table 1 presents the details of the 36 participating studies. The studies are listed by their design and, within each type of design, by the median year when the endometrial cancers were diagnosed in each study. Most studies were done in Europe or North America, with three from Asia, one from Australia, one from South Africa, and one multinational study. Together, the analyses included 27 276 women with endometrial cancer (cases) and 115 743 women without endometrial cancer (controls). The

Discussion

This international collaboration has brought together and re-analysed almost all of the available epidemiological evidence on the reduction in endometrial cancer incidence associated with oral contraceptive use, and includes data from 27 000 women with endometrial cancer from 36 studies. Overall, the longer women had used oral contraceptives, the greater the reduction in the risk of endometrial cancer. On average, every 5 years of oral contraceptive use was associated with a relative risk of

References (60)

  • KJ Wernli et al.

    Menstrual and reproductive factors in relation to risk of endometrial cancer in Chinese women

    Cancer Causes Control

    (2006)
  • VW Setiawan et al.

    Racial/ethnic differences in endometrial cancer risk: the multiethnic cohort study

    Am J Epidemiol

    (2007)
  • HP Yang et al.

    Endometrial cancer risk factors by 2 main histologic subtypes: the NIH-AARP Diet and Health Study

    Am J Epidemiol

    (2013)
  • L Dossus et al.

    Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

    Int J Cancer

    (2010)
  • NR Cook et al.

    Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial

    JAMA

    (2005)
  • L Gren et al.

    Recruitment methods employed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    Clin Trials

    (2009)
  • E Epstein et al.

    A population-based cohort study on the use of hormone treatment and endometrial cancer in southern Sweden

    Int J Cancer

    (2009)
  • M Lof et al.

    Birth weight in relation to endometrial and breast cancer risks in Swedish women

    Br J Cancer

    (2007)
  • E Friberg et al.

    Coffee drinking and risk of endometrial cancer—a population-based cohort study

    Int J Cancer

    (2009)
  • V Beral et al.

    Endometrial cancer and hormone-replacement therapy in the Million Women Study

    Lancet

    (2005)
  • Combination oral contraceptive use and the risk of endometrial cancer. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development

    JAMA

    (1987)
  • JL Stanford et al.

    Oral contraceptives and endometrial cancer: do other risk factors modify the association?

    Int J Cancer

    (1993)
  • MC Pike et al.

    Estrogen-progestin replacement therapy and endometrial cancer

    J Natl Cancer Inst

    (1997)
  • PA Newcomb et al.

    Patterns of postmenopausal progestin use with estrogen in relation to endometrial cancer (United States)

    Cancer Causes Control

    (2003)
  • E Weiderpass et al.

    Use of oral contraceptives and endometrial cancer risk (Sweden)

    Cancer Causes Control

    (1999)
  • E Weiderpass et al.

    Organochlorines and endometrial cancer risk

    Cancer Epidemiol Biomarkers Prev

    (2000)
  • BL Strom et al.

    Case-control study of postmenopausal hormone replacement therapy and endometrial cancer

    Am J Epidemiol

    (2006)
  • MH Tao et al.

    Oral contraceptive and IUD use and endometrial cancer: a population-based case-control study in Shanghai, China

    Int J Cancer

    (2006)
  • LA Brinton et al.

    Reproductive risk factors for endometrial cancer among Polish women

    Br J Cancer

    (2007)
  • LS Cook et al.

    Hormone contraception before the first birth and endometrial cancer risk

    Cancer Epidemiol Biomarkers Prev

    (2014)
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    Collaborators listed in appendix p 3

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