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Cancer Epidemiology, Biomarkers & Prevention
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Review

Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review

Jennifer M. Gierisch, Remy R. Coeytaux, Rachel Peragallo Urrutia, Laura J. Havrilesky, Patricia G. Moorman, William J. Lowery, Michaela Dinan, Amanda J. McBroom, Vic Hasselblad, Gillian D. Sanders and Evan R. Myers
Jennifer M. Gierisch
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Remy R. Coeytaux
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Rachel Peragallo Urrutia
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Laura J. Havrilesky
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Patricia G. Moorman
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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William J. Lowery
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Michaela Dinan
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Amanda J. McBroom
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Vic Hasselblad
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Gillian D. Sanders
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Evan R. Myers
1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; 2Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of 3Medicine, 4Community and Family Medicine, 5Obstetrics and Gynecology, and 6Biostatistics and Bioinformatics, Duke University School of Medicine; 7Duke Cancer Institute, Duke University Health System; 8Duke Clinical Research Institute, Durham; and 9Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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DOI: 10.1158/1055-9965.EPI-13-0298 Published November 2013
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Abstract

Oral contraceptives may influence the risk of certain cancers. As part of the AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, we conducted a systematic review to estimate associations between oral contraceptive use and breast, cervical, colorectal, and endometrial cancer incidence. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews. Study inclusion criteria were women taking oral contraceptives for contraception or ovarian cancer prevention; includes comparison group with no oral contraceptive use; study reports quantitative associations between oral contraceptive exposure and relevant cancers; controlled study or pooled patient-level meta-analyses; sample size for nonrandomized studies ≥100; peer-reviewed, English-language; published from January 1, 2000 forward. Random-effects meta-analyses were conducted by estimating pooled ORs with 95% confidence intervals (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial cancers studies. Breast cancer incidence was slightly but significantly increased in users (OR, 1.08; CI, 1.00–1.17); results show a higher risk associated with more recent use of oral contraceptives. Risk of cervical cancer was increased with duration of oral contraceptive use in women with human papillomavirus infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86; CI, 0.79–0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43–0.77) were significantly reduced by oral contraceptive use. Compared with never use, ever use of oral contraceptives is significantly associated with decreases in colorectal and endometrial cancers and increases in breast cancers. Although elevated breast cancer risk was small, relatively high incidence of breast cancers means that oral contraceptives may contribute to a substantial number of cases. Cancer Epidemiol Biomarkers Prev; 22(11); 1931–43. ©2013 AACR.

Introduction

Oral contraceptives, the most common form of effective and reversible contraception in the United States (1), significantly decrease the personal and societal burdens associated with unintended or unwanted pregnancy (2, 3). Oral contraceptives also have significant noncontraceptive health benefits such as improving acne and regulating dysmenorrhea (4–7). However, oral contraceptive use is not without risks. Many studies show serious adverse events associated with oral contraceptive use including venous thromboembolic disease, myocardial infarction, and stroke (8–10).

In addition to the risk of acute harms, the use of oral contraceptives may influence the risk of certain cancers (11). Oral contraceptive use may promote or initiate tumors of the breast or cervix (12–14). For breast cancer, these risks may be even greater for women at elevated risk due to family history of cancer or genetic mutation carrier status (e.g., BRCA1/2); however, results from studies are inconclusive (15, 16). Oral contraceptive use has also been associated with a greater risk of certain clinically challenging types of breast tumors (17). Conversely, oral contraceptive use is associated with significant reductions in colorectal, endometrial, and ovarian cancers (11, 18–20). A recent systematic review and meta-analysis supports a significant risk reduction for ovarian cancer incidence and mortality associated with the use of oral contraceptives (20).

Assessing the risk of cancer associated with oral contraceptive use is fraught with difficulties. For example, cancer is a disease with a long latency period, and the time between exposure to oral contraceptives and diagnosis of cancer may span decades. Also, temporal variations in oral contraceptive formulations available on the market and used over a woman's lifetime may influence associations between cancer risk and oral contraceptive use. Furthermore, patterns of oral contraceptive use over a lifetime may be influenced by factors that also affect cancer risks (e.g., gravidity, parity, breastfeeding). Duration of oral contraceptive use or length of time since ceasing use (i.e., recency) may also modify the risk of cancers associated with oral contraceptives (13, 21).

We conducted a systematic review and meta-analysis, sponsored by the Agency for Healthcare Research and Quality (AHRQ) and the Centers for Disease Control and Prevention (CDC), to inform the use of oral contraceptives to reduce the risk of ovarian cancer (20). In addition to the primary question regarding ovarian cancer, we also addressed other harms and benefits of oral contraceptive use. In this article, we examine the evidence for associations between oral contraceptive use and the risks of developing 4 cancers: breast, cervical, colorectal, and endometrial. When possible, we conducted meta-analyses of the literature to assess the risk of developing these cancers following oral contraceptive use; we also examined risk by duration of oral contraceptive use and time since last oral contraceptive use (20).

Materials and Methods

We followed the methodology recommended in AHRQ's “Methods Guide for Effectiveness and Comparative Effectiveness Reviews” (22). Methods are summarized here, with complete details provided in the full AHRQ report (20).

Search strategy

In collaboration with an experienced librarian, we conducted searches of PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov to identify relevant published literature. Our searches were date-limited to articles published from January 1, 1990 to June 29, 2012. For the outcomes presented in this article, we restricted the results to 2000 forward for the following reason. Formulations of oral contraceptives have been changed and updated almost continuously since their introduction to the U.S. market in 1957; such changes have not occurred at discrete time points. Also, year-by-year market share, duration of use, and patterns of use are not readily available and would vary based on the country in which a given study was conducted. Realizing the inaccuracy of any discrete cutoff date with regard to current oral contraceptive formulations, we limited the publication years of included studies to those published from 2000 forward to try to maximize the proportion of subjects who used oral contraceptive formulations similar to those currently on the market. We supplemented electronic searches with a manual search of citations from key review articles. Exact search strings are provided in Appendix A of the full AHRQ report (20).

Selection criteria

Inclusion criteria for studies relevant to this article were: (i) study includes women taking oral contraceptives for contraception or primary prevention of ovarian cancer; (ii) study includes comparison group with no use of combination or progestin-only oral contraceptives (either no contraceptive method at all or contraceptive methods other than combination or progestin-only oral contraceptives); (iii) study reports quantitative associations between exposure to oral contraceptives and breast, cervical, colorectal, or endometrial cancer incidence; (iv) controlled study (randomized trials, cohort studies, case–control studies) or pooled patient-level meta-analyses; (v) sample size for nonrandomized studies ≥100 subjects; (vi) study is peer-reviewed and English-language; and (vii) published on or after January 1, 2000. Exclusion criteria were: (i) study reports outcomes related to the use of oral contraceptives only for contraception, or in specialized populations such as women immediately post-termination of pregnancy, or women receiving assisted reproductive technologies; (ii) study does not provide a description of the oral contraceptive formulation(s) or length of oral contraceptive use; or (iii) publication type is editorial, review, or letter to the editor.

Reviewer pairs used prespecified criteria to assess titles and abstracts. Full-text articles included by either reviewer underwent further evaluation. Eligibility decisions and disagreements were reconciled through discussion or by a third reviewer. For included studies, we abstracted data on study populations, interventions, outcomes, quality, and applicability. We used criteria developed by AHRQ to assess study quality, summarized as good, fair, or poor (22). Quality ratings for individual articles within study groupings could differ based on articles' reporting quality, evaluated outcomes, and statistical and analytical methods used. We screened and abstracted data using DistillerSR software (Evidence Partners Inc.).

Data synthesis

When at least 3 studies were available with comparable study designs and outcomes, we conducted random-effects meta-analyses grouped by study design (case–control or cohort study) and estimated pooled ORs with 95% confidence intervals (CI). As there were no significant differences by design, we used a random-effects model to combine subgroups and estimate the overall effect. When studies reported multiple models, we used the most adjusted model. We evaluated heterogeneity visually and with the Cochran Q statistic using a threshold P < 0.10. We included pooled analyses in our meta-analyses if all these conditions were met by the pooled analysis: none of the individual articles were already included in the meta-analysis, at least half of the studies were published on or after January 1, 2000, and data were presented such that their inclusion in meta-analysis was feasible.

Not all studies meeting criteria for inclusion in the review were included in meta-analyses. The reasons for exclusion from meta-analysis were (i) study populations that represented specialized subgroups (e.g., BRCA mutation, family history, age at diagnosis ≤ 45 years, cancer subtype); (ii) studies that reported a subset of results from the same study as another article already included in the analysis; and (iii) studies that did not report an OR for ever oral contraceptive use versus never oral contraceptive use. When studies gave results only by subgroup (premenopausal, postmenopausal), we combined subgroups to generate an estimate only when the combined group represented a broad population. When possible, we conducted sensitivity analyses by including only U.S.-based studies. These analyses were conducted using Comprehensive Meta-Analysis Version 2 (23).

We estimated the increase or decrease in absolute risk of cancer from estimates of the lifetime incidence of malignant cases for women beginning at age 45 years generated using the National Cancer Institute's DevCan software (24), estimated lifetime ever use of oral contraceptives from the National Survey of Family Growth (25), and the ORs (with 95% CIs) produced in our meta-analyses. We then calculated the number needed to treat (NNT) or number needed to harm (NNH) by taking the inverse of the absolute risk. Because we were unable to conduct meta-analysis of the association of oral contraceptive use and cervical cancer among populations that were selected for HPV-positive status, we were unable to generate estimates of change in absolute risk.

When we had sufficient studies to assess the effect of duration of oral contraceptive use, we used a random-effects model to compute ORs. We required that the ORs were given relative to no oral contraceptive use and that the population studied was not restricted to a particular subpopulation. The challenge of conducting a meta-analysis on duration of oral contraceptive use is that individual studies reported ORs for different duration intervals. We assumed that the logarithm of each OR could be described by a linear model. The model included a random-effects term, σ2, as well as terms for time point intervals. We then used independent variables to create the time period desired. The model was fitted using SAS PROC NLMIXED (SAS Institute Inc.; 2009) with “subject” set to the particular study.

We evaluated strength of evidence using the approach described in AHRQ's “Methods Guide” (22, 26).

Results

Of the 6,476 unique citations screened, we identified 44 studies relevant to breast, 12 to cervical, 11 to colorectal, and 9 to endometrial cancers (Fig. 1). Several included studies were relevant to more than one outcome of interest. All studies were observational; we did not identify any eligible randomized controlled trials. We did not identify any qualitative difference between breast, cervical, colorectal, or endometrial cancers and oral contraceptive use based on probable dates of exposure when examined by study recruitment date versus publication date.

Figure 1.
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Figure 1.

Literature flow diagram. *Note that a given study may address more than one outcome group. MI, myocardial infarction; OC, oral contraceptive; RCT, randomized controlled trial; VTE, venous thromboembolism.

Breast cancer incidence

Forty-four studies (19 good quality, 25 fair, and 3 poor) evaluated the association between oral contraceptive use and breast cancer incidence (16, 17, 27–78). Of these, 29 were case–control studies, 14 were cohort studies, and 1 was a pooled analysis (Supplementary Table S1). Fifteen case–control studies (38,682 women; refs. 16, 27–30, 33, 37, 48, 49, 51, 54, 56, 73, 74, 78) and 8 cohort studies (317,341 women across 5 studies and 3,981,072 person-years across 3 studies; refs. 59–61, 63, 65, 67–69) met criteria for meta-analysis examining ever versus never oral contraceptive use. Figure 2 shows the results suggesting that a history of oral contraceptive use slightly but significantly increases breast cancer incidence compared with never oral contraceptive use (OR, 1.08; 95% CI, 1.00–1.17), with a Q value of 73.35 for 21 degrees of freedom (DF); P < 0.001. In a sensitivity analysis of only U.S.-based studies, effect sizes were smaller and no longer statistically significant (OR, 1.03; CI, 0.93–1.14). On the basis of the point estimates of the meta-analyses, the approximate increase in estimated lifetime absolute risk of breast cancer from ever use of oral contraceptives is 0.89% (NNH, 113).

Figure 2.
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Figure 2.

Forest plot of ever versus never oral contraceptive use and breast cancer incidence.

Fourteen studies (16, 27, 30, 36, 37, 44, 48, 49, 54, 59–61, 63, 69, 78) met criteria for the meta-analysis examining duration of oral contraceptive use. We found no time-dependent relationship as a function of duration of use: 1–12 months (OR, 0.95; CI, 0.83–1.09); 13–60 months (OR, 1.03; CI, 0.92–1.15); 61–120 months (OR, 1.01; CI, 0.90–1.13); and >120 months (OR, 1.04; CI, 0.93–1.17). Heterogeneity was significant (t = 5.84, 19 DF, P < 0.0001).

Eleven studies (16, 27, 30, 33, 37, 38, 46, 49, 51, 53, 59, 61) met criteria for the meta-analysis examining time since last oral contraceptive use. Results show a time-dependent relationship as a function of time since last oral contraceptive use, with higher risk associated with more recent use of oral contraceptives and ORs that approach 1 (no effect) by ≥20 years of use: 0–5 years (OR, 1.21; CI, 1.04–1.41); 5–10 years (OR, 1.17; CI, 0.98–1.38); 10–20 years (OR, 1.13; CI, 0.97–1.31); >20 years (OR, 1.02; CI, 0.88–1.18). Heterogeneity was significant (σ = 0.12; t = 4.95, 11 DF, P = 0.0004).

The strength of evidence for the effect of ever oral contraceptive use on breast cancer incidence was moderate. Most studies were of good or fair quality, exhibited consistent findings, and confidence interval for summary estimate were precise. However, all included studies were observational; thus there may be some risk of bias due to limitations of the study designs. The strength of evidence was low for both duration of use and time since last use for risk of breast cancer incidence; results were inconsistent with a high level of heterogeneity across studies.

Cervical cancer incidence

Twelve studies (5 good, 4 fair, 4 poor quality) evaluated the association between oral contraceptive use and cervical cancer incidence (63, 65, 66, 69, 70, 73, 79–87), including 2 articles from an International Agency for Research on Cancer (IARC) study representing distinct populations (86, 87). Of these, 9 were case–control studies, 3 were cohort studies, and 1 was a pooled analysis. Only 2 studies were conducted with U.S.-based populations (Supplementary Table S2).

Persistent infection with one or more oncogenic HPV types is required for cervical carcinogenesis; thus, women who are HPV-positive represent the most relevant population to assess the risks for cervical cancer associated with oral contraceptive use. Only 3 studies (80, 83, 86) assessed the association between oral contraceptive use and cervical cancer among women who are HPV-positive. Limited studies across comparisons precluded quantitative synthesis; we summarize each study below.

One fair-quality study (86) pooled data from 8 case–control studies of HPV-positive patients with cervical cancer. Ever use of oral contraceptives was associated with a statistically nonsignificant increase in invasive cervical cancer (OR, 1.29; CI, 0.88–1.91) and cervical cancer in situ (OR, 2.54; CI, 0.95–6.78). However, duration of use was significantly associated with cancer incidence such that HPV-positive women who used oral contraceptives for 5 to 9 years (OR, 2.82; CI, 1.46–5.42) and ≥10 years (OR, 4.03; CI, 2.09–8.02) experienced a significant increase in the risk of cervical cancers compared with never users. This estimate did not vary by time since first or last use; the trend was not observed for women who used oral contraceptives for <5 years.

Two case–control studies (80, 83), both rated poor quality, also assessed the risk of cervical cancer associated with oral contraceptive use among HPV-positive women. One study (80) recruited hospital-based HPV-positive cases and controls in Lima, Peru. Results of this study were included in the pooled analysis above and, thus, could not be combined again. Compared with HPV-positive controls, HPV-positive women who had ever used oral contraceptives were at elevated risk of cervical cancer compared with women who had never used oral contraceptives (OR, 2.7; CI, 0.90–8.4), but the contrast was not significant. This study did not compute any analysis by duration of use.

The other case–control study (83) assessed the association between oral contraceptive use and cervical cancer among hospital-based HPV-positive cases and HPV-positive community controls in the United States. This study assessed duration of oral contraceptive use; ever use versus never use was not calculated. Increasing the duration of oral contraceptive use—categorized as <5, 5–10, and >10 years—was associated with a decrease in cervical cancers. This trend was significant only in women with <5 years of use compared with never users (OR, 0.6; CI, 0.4–0.9).

In populations that were not selected for HPV-positive status, 6 case–control studies representing 5,436 women (73, 79, 81, 82, 84, 85) and 3 cohort studies (63, 65, 69) representing 3,981,072 person-years met criteria for the meta-analysis examining ever versus never oral contraceptive use. Figure 3 shows results indicating increased odds of cervical cancer for women who had ever used oral contraceptives compared with women who never used oral contraceptives (OR, 1.21; CI, 0.91–1.61), but the comparison was not significant. There was a large amount of heterogeneity (Q = 25.52, 7 DF, P < 0.001), possibly due to differences in HPV status among studies, which made the estimates unstable. We could not conduct sensitivity analysis by U.S.-based studies because only one study was conducted within the United States. Results from this case–control study (79) show a statistically significant increase in risk with ever use of oral contraceptives (OR, 2.7; CI, 1.2–5.8).

Figure 3.
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Figure 3.

Forest plot of ever versus never oral contraceptive use and cervical cancer incidence.

Six studies (63, 79, 81, 82, 85, 87) met criteria for the meta-analysis examining duration of oral contraceptive use. Results show no time-dependent relationship as a function of duration: 1–60 months (OR, 0.99; CI, 0.58–1.70) and >60 months (OR, 1.47; CI, 0.91–2.38). Heterogeneity was significant (t = 4.72; 5 DF, P = 0.0033).

The strength of evidence for the effect of ever oral contraceptive use on cervical cancer incidence among HPV-positive women was insufficient. Only 3 studies assessed risk in HPV-positive women, and most were of poor quality. Results were inconsistent, sensitivity analysis yielded qualitatively different estimates of effects, and CIs were wide. Studies did not control for factors that may influence risk such as age at first use by duration or age at sexual debut, which is likely highly correlated with age at first use. Future studies could influence magnitude and, possibly, direction of effect.

Colorectal cancer incidence

Eleven studies (4 good, 6 fair, 1 poor quality) evaluated the association between oral contraceptive use and colorectal cancer incidence (63, 65, 66, 68, 88–95). Of these, 3 were case–control studies, 7 were cohort studies, and 1 was a pooled analysis. Nine studies were conducted in Western countries and 2 in China (Supplementary Table S3).

Three case–control studies (88–90), 1 pooled analysis (94), and 7 cohort studies (63, 65, 68, 91–93, 95) representing 503,816 women across 8 studies and 2,969,189 person-years across 3 studies met criteria for the meta-analysis examining ever versus never oral contraceptive use. Figure 4 shows the results showing a decrease in the risk of colorectal cancers among women who ever used oral contraceptives compared with women who never used oral contraceptives (OR, 0.86; CI, 0.79–0.95; Q = 17.17, P < 0.046). We conducted sensitivity analyses of studies that included only patients from the United States; results were similar to analyses containing all studies, but the confidence interval eclipsed 1 (OR, 0.83; CI, 0.69–1.01). On the basis of the point estimates of the meta-analyses, the approximate decrease in absolute risk of colorectal cancer is 0.76% (NNT 132).

Figure 4.
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Figure 4.

Forest plot of ever versus never oral contraceptive use and colorectal cancer incidence.

Ten studies (63, 65, 68, 88–92, 94, 95) met criteria for the meta-analysis examining duration of oral contraceptive use. We categorized duration of use into 2 intervals and found no time-dependent relationship as a function of duration: 1–60 months (OR, 0.88; CI, 0.77–1.01) and >60 months (OR, 0.88; CI, 0.76–1.01). There was no significant heterogeneity (t = 1.52; 9 DF, P = 0.164).

The strength of evidence for the effect of oral contraceptive use on colorectal cancer incidence was moderate. Results were consistent across studies, and the summary estimate showed high precision with a tight CI. Future studies will not likely have an impact on the direction of effect but may slightly influence the magnitude of the effect. The strength of evidence for duration was insufficient; the test was underpowered and we found significant heterogeneity.

Endometrial cancer incidence

Nine studies (6 good, 2 fair, 1 poor quality) evaluated the association between oral contraceptive use and endometrial cancer incidence (63, 65, 66, 69, 70, 73, 96–100). Of these, 4 were case–control studies and 5 were cohort studies. Only 2 studies were conducted in the United States (Supplementary Table S4).

Three case–control studies (73, 97, 100) and 4 cohort studies (63, 65, 69, 98) representing 308,198 women (within 4 studies) and an additional 3,981,072 person-years (within the other 3 studies) were included in this meta-analysis examining ever versus never oral contraceptive use. Figure 5 shows results indicating a protective effect for endometrial cancer associated with ever oral contraceptive use (OR, 0.57; CI, 0.43–0.77). Heterogeneity was significant (Q = 26.11, 6 DF, P < 0.001). We also explored how our findings changed when including only U.S.-based studies. Only one study was conducted with patients from the United States and reported a somewhat greater protective effect than summary estimates for all studies (OR, 0.34; CI, 0.25–0.47). On the basis of the point estimates of the meta-analyses, the approximate decrease in absolute risk of endometrial cancer is 1.77% (NNT 60).

Figure 5.
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Figure 5.

Forest plot of ever versus never oral contraceptive use and endometrial cancer incidence.

Discussion

Our results are confirmatory of initial analyses and reviews, including those which included studies published before 2000. This evidence synthesis highlights some of the tradeoffs about nonreproductive outcomes that patients and providers need to consider with the use of oral contraceptives: increased risk for some cancers (breast and cervical) but decreased risk for others (colorectal and endometrial). Other considerations include decreased risk of ovarian cancer (101) and increased risk for thromboembolic events (102). Estimating the overall balance of benefit and harm is difficult from a technical sense and because the timing of the outcomes affected by oral contraceptive use is variable—some risks and benefits are seen only during use, whereas others occur 20 to 30 years in the future. Moreover, different patients may well have different values for those outcomes.

We found that the risk of breast cancer was slightly—but significantly—elevated for women who have ever used oral contraceptives compared with women who have never used oral contraceptives. Although the relative increase in risk was small (OR, 1.08), the relatively high incidence of breast cancer diagnosis means that oral contraceptive use may contribute to a substantial number of cases. We found no time-dependent relationship as a function of duration of oral contraceptive use. Duration results should be interpreted with caution; there was significant heterogeneity, and the test was underpowered—which is not surprising, given that breast cancer is relatively uncommon during the ages when women are most likely to be using oral contraceptives. We also found that women with more recent use had an elevated risk of breast cancer, with decreasing risk over time, so that by 10 years since last use, the risk among users was equivalent to never users.

Our results are consistent with results of other meta-analyses and pooled analyses that identified a small increase in the relative risk of breast cancer associated with having ever used oral contraceptives—a risk that diminishes over time since last use (12, 103). The Collaborative Group on Hormonal Factors in Breast Cancer, a collaborative reanalysis of individual data in 153,536 women, found a small but significant increase in the relative risk of breast cancer (OR, 1.07 ± 0.02; ref. 12). Similar to our results, the Collaborative Group did not identify an increase in risk with increasing duration of use or after discontinuation of use for ≥10 years. Another recent meta-analysis of premenopausal breast cancer across 37 studies found a somewhat larger increase in the risk (OR, 1.19; CI, 1.09–1.29), with the greatest risk associated with oral contraceptive use before first full-term pregnancy (OR, 1.44; CI, 1.28–1.62; ref. 104). These results support our finding that recent use (≤5 years) is associated with an increased risk of breast cancer. Women who delay first full-term pregnancies may also be more likely to be recent users of oral contraceptives relative to a breast cancer diagnosis. These results cannot be directly compared with ours, as this meta-analysis was restricted to premenopausal women or women <50 years who may be at elevated risk due to other factors (e.g., genetic mutations) or represent cancer subtypes that differentially affect younger women. An alternative explanation of an association between oral contraceptive use and increased incidence may be more surveillance in women who use oral contraceptives. Women who use oral contraceptives must come in contact with the health care system on a regular basis, thus increasing their chances of receiving referrals for preventive screenings such as mammography.

We found no significant increase in the risk of cervical cancer among ever oral contraceptive users compared with never users across 9 pooled studies. We also found no time-dependent relationship as a function of duration of oral contraceptive use. It is important to note that this contrast was underpowered with only 5 included studies. However, women having long-term use of oral contraceptives (≥5 years) were at an elevated but not statistically significant risk of cervical cancer compared with never users.

Three studies (2,592 women) assessed oral contraceptive use and cervical cancer incidence among HPV-positive women. Results were similar to those of women not selected for HPV status. Many studies did not control for factors that may influence risk, such as age at first oral contraceptive use by duration or age at sexual debut, which is likely highly correlated with age at first use. Future research is needed to assess the additional cervical cancer risk associated with oral contraceptive use among HPV-positive women. However, both studies reported statistically significant increased risk of death with ≥8 years of oral contraceptive use compared with never use.

Our cervical cancer results differ in some ways from other evidence syntheses published over the last 10 years. Smith and colleagues (13) pooled study-level data across 28 studies and found an overall significant increase in the risk of cervical cancer when comparing ever versus never users of hormonal contraceptives [relative risk (RR), 1.2; CI, 1.1–1.3). We found a similar increase in the risk of cervical cancers, but our summary estimate was not significant. Both our review and the Smith study found the risk of cervical cancer increased with prolonged exposure. This effect weakened but remained significant when stratifying duration by time since use. For our review, this effect was significant only for women who used oral contraceptives for ≥5 years compared with never users; we did not have sufficient studies to stratify by time since last use. The International Collaborative of Epidemiological Studies of Cervical Cancer undertook a collaborative patient-level reanalysis of 24 observational studies (105). Results expand the duration by recency effect. The analysis found that excess risk of cervical cancers increases with duration of use, but this effect declined after discontinuing oral contraceptives and was equivalent to the risk of nonusers after 10 years of nonuse.

Key methodological differences between our study and the 2 recent syntheses preclude drawing exact comparisons. First, we included only studies of invasive cervical cancers; other studies also included carcinoma in situ and cervical intraepithelial neoplasia grade 3. It is likely that effects differ between invasive cancers and cancer precursor lesions. In fact, a case–case comparison in the collaborative reanalysis showed significant differences in the risks for in situ and invasive cervical cancers for nearly every category of time since last use by duration of use. Second, we included studies that assessed only the effects of oral contraceptives; the 2 other recent syntheses included all forms of hormonal contraceptives. It is possible that formulation differences contribute to some of the differences between our results and their findings. However, the collaborative reanalysis reported separate findings for progestin-only injectable contraceptives and found a similar pattern to those reported for oral contraceptives. Third, we did not include the 3 studies conducted with women selected for HPV infection status. The effects of this decision appear to be negligible; both prior reviews noted similar patterns of findings when controlling for HPV status as a covariate (13) compared with HPV uncontrolled studies or among the subset of women with a confirmed HPV infection compared with populations not selected for HPV status (105). Last, we date-limited our search from 2000 forward to minimize the effect of older formulations; other studies had no such date restrictions. Despite these differences, we found similar patterns of increased risk by duration of use. There is no direct evidence to suggest that cervical cancer screening recommendations should be different based on duration of oral contraceptive use.

We found that the risk of colorectal cancer was significantly decreased for women who have ever used oral contraceptives compared with women who have never used oral contraceptives. However, we found no evidence of a time-dependent relationship as a function of duration. Duration results should be interpreted with caution; the test was underpowered.

Our results are similar to 2 other evidence syntheses that also assessed the risk of colorectal cancers associated with oral contraceptive use (11, 106). These meta-analyses both found a pooled relative risk of approximately 0.82, which is comparable to our pooled findings. These reviews also found no increase in the protective effect by duration of use. The similarity between our findings and those of the other 2 reviews is noteworthy. We limited our studies from January 2000 forward so that we had a greater probability of capturing a set of studies with newer oral contraceptive formulations that may confer differential effects. Thus, we shared no studies in common with the study by Fernandez and colleagues (106), and we excluded 12 older or non-English studies and included 5 newer studies (63, 68, 90, 93, 95) compared with the systematic review by Bosetti and colleagues (11). Similarity in our findings with these earlier evidence syntheses suggests that oral contraceptives confer a significant protective effect for colorectal cancer, and future research could investigate oral contraceptives potential as a beneficial therapy for chemoprevention.

We identified 9 studies that evaluated the association between oral contraceptive use and the incidence of endometrial cancers; 7 were included in our meta-analysis to assess ever versus never oral contraceptive use. We found a significant protective effect with ever oral contraceptive use and a time-dependent relationship as a function of duration categorized as <60 and ≥60 months of total use.

Our study is one of the few systematic reviews and meta-analyses to summarize the evidence on the effects of oral contraceptives on endometrial cancers. Grimes and colleagues (107) conducted a systematic review and qualitative synthesis of studies up to 1993. They identified 13 case–control studies with protective ORs ranging from 0.1 to 0.6, with most effects clustering around 0.5. Two of the 3 cohort studies identified also found protective effects of oral contraceptive use. Schlesselman and colleagues (108) conducted a meta-analysis of 11 case–control studies. A significant duration trend was reported such that longer durations of use conferred greater protection (RR, 0.44 for 4 years of use; RR, 0.33 for 8 years of use; RR, 0.28 for 12 years of use; P < 0.0001). We found a similar trend but used a different analytic approach; direct comparisons are difficult to draw. This meta-analysis also reported on time since last use and found that the protective effect of oral contraceptives is diminished after they are discontinued but still persists even 20 years after cessation. We did not have sufficient studies to assess the effect of time since last use. Protective effects of oral contraceptives may vary with formulation. However, our results are similar to other studies conducted in the 1990s that may have included different formulations based on market availability. Unfortunately, there are limited data on the formulations used in the majority of the studies reviewed, and it is likely that the distribution of formulations in the studies included in this review is different compared to contemporary oral contraceptive formulation distribution. If the association between oral contraceptive use and cancer varies based on formulation, particularly estrogen dosage, and type of progestin, then estimates of reduction or increases in future cancer risk among current pill users are subject to considerable additional uncertainty. Our results—in combination with other evidence reviews—confirm that oral contraceptives confer a significant protective effect on the risk of endometrial cancers.

Limitations

While we conducted a comprehensive systematic review and evidence synthesis of the current research on oral contraceptive use and the incidence of breast, cervical, colorectal, and endometrial cancers, there are limitations to our approach and findings. As expected, we identified no randomized trials; such studies are not likely feasible. Thus, we included only observational studies in our meta-analyses. Even the highest quality observational studies are susceptible to multiple forms of bias (e.g., confounding). Most included studies adjusted for multiple likely sources of cofounding; when possible, we used the most adjusted point estimates in our meta-analyses. Recall bias is also a common source of diminished quality in observational studies. Our findings were remarkably similar across case–control studies and cohort studies, which suggests a lack of evidence for recall bias of oral contraceptive use across study types. Also, we found significant heterogeneity across many of our comparisons. We included a diverse group of studies conducted across the world; differences in study populations and geographic variability in other risk factors not routinely assessed (e.g., access to health care) likely contributed to this heterogeneity. This may be particularly true for cancers such as breast, cervical, and colorectal, where screening can affect both incidence and mortality and where there may be associations between oral contraceptive use and screening behaviors. Sensitivity analyses using only U.S.-based studies (or with patients from the United States) showed similar patterns to unrestricted analyses. Also, studies varied considerably in the type and specification of covariates, which may be a likely source of heterogeneity. To try to maximize the proportion of subjects who used oral contraceptive formulations similar to those currently on the market, we included only studies published in 2000 and later. However, study publication date is a gross estimate of oral contraceptive formulation exposure because observational studies published since 2000 still represents some cohorts exposed to earlier formulations. It may have been preferable to limit studies by year of diagnosis instead of publication date. Yet many of our findings are consistent with other meta-analyses without date restrictions, which suggest that current oral contraceptive formulations may have similar carcinogenic or protective effects compared with older formulations. Still, given the long latent period between exposure and tumor development, it is likely that recent publications may not fully assess the effect of formulations introduced in the past 20 years.

Conclusion

This systematic review of the literature identified several gaps in the evidence that warrant future investigation. Several subgroups deserve further attention; there are limited data on the effects of oral contraceptives on cancer risk in women at elevated risk of malignancy due to behavioral risk factors such as smoking, heavy alcohol consumption, obesity, or physical inactivity. These factors are known to be associated with cancer development, and so behavioral risk factors may modify the association between oral contraceptives and cancers. We found that duration of use conferred a different pattern of risk, but we found limited support of a time-dependent relationship. Because the benefits and risks associated with oral contraceptive use differ by pattern of use, more research is needed on the interaction of different patterns of use (e.g., duration by time since last use, age at initiation by duration) on the risk of breast, cervical, colorectal, and endometrial cancers to optimize the risks and benefits of oral contraceptive use.

Quantifying the potential impact of changes in oral contraceptive formulations is difficult. Although our analyses were based on more recently published data, and we did not identify an obvious association based on probable dates of exposure within these studies, the long lag time between “typical” exposure to oral contraceptives and incident cancers means that the distribution of formulations among subjects in even the most recent literature is likely to be different than the distribution among current oral contraceptive users. This uncertainty affects both estimated harms (increased risk of breast cancer) and benefits (decreased risk of endometrial and colorectal cancer).

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Disclaimer

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by AHRQ, CDC, the U.S. Department of Health and Human Services, or the U.S. Department of Veterans Affairs.

Authors' Contributions

Conception and design: J.M. Gierisch, R.M. Coeytaux, R.P. Urrutia, L.J. Havrilesky, A.J. McBroom, G.D. Sanders, E.R. Myers

Development of methodology: J.M. Gierisch, R.M. Coeytaux, R.P. Urrutia, L.J. Havrilesky, A.J. McBroom, G.D. Sanders, E.R. Myers

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): J.M. Gierisch, R.M. Coeytaux, R.P. Urrutia, L.J. Havrilesky, P.G. Moorman, W.J. Lowery, A.J. McBroom, G.D. Sanders

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): J.M. Gierisch, R.M. Coeytaux, R.P. Urrutia, P.G. Moorman, W.J. Lowery, M. Dinan, A.J. McBroom, V. Hasselblad, G.D. Sanders, E.R. Myers

Writing, review, and/or revision of the manuscript: J.M. Gierisch, R.M. Coeytaux, R.P. Urrutia, L.J. Havrilesky, P.G. Moorman, W.J. Lowery, M. Dinan, A.J. McBroom, G.D. Sanders, E.R. Myers

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): J.M. Gierisch, A.J. McBroom

Study supervision: G.D. Sanders

Grant Support

All authors received support and this project was funded under Contract No. 290-2007-10066-I from the Agency for Healthcare Research and Quality (AHRQ) and the Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services.

Acknowledgments

The authors thank Liz Wing, for editorial assistance; Kathryn Roth Lallinger and Michael Musty, for project coordination; and Megan von Isenburg, for help with the literature search and retrieval.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Received March 19, 2013.
  • Revision received August 21, 2013.
  • Accepted August 27, 2013.
  • ©2013 American Association for Cancer Research.

References

  1. 1.↵
    1. Mosher WD,
    2. Jones J
    . Use of contraception in the United States: 1982–2008. Vital Health Stat 23 2010;1–44.
  2. 2.↵
    1. Dinger J,
    2. Do Minh T,
    3. Buttmann N,
    4. Bardenheuer K
    . Effectiveness of oral contraceptive pills in a large U.S. cohort comparing progestogen and regimen. Obstet Gynecol 2011;117:33–40.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Dinger JC,
    2. Cronin M,
    3. Mohner S,
    4. Schellschmidt I,
    5. Minh TD,
    6. Westhoff C
    . Oral contraceptive effectiveness according to body mass index, weight, age, and other factors. Am J Obstet Gynecol 2009;201:263.e1–9.
    OpenUrlPubMed
  4. 4.↵
    1. Spencer AL,
    2. Bonnema R,
    3. McNamara MC
    . Helping women choose appropriate hormonal contraception: update on risks, benefits, and indications. Am J Med 2009;122:497–506.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Haider A,
    2. Shaw JC
    . Treatment of acne vulgaris. JAMA 2004;292:726–35.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Lindh I,
    2. Ellstrom AA,
    3. Milsom I
    . The effect of combined oral contraceptives and age on dysmenorrhoea: an epidemiological study. Hum Reprod 2012;27:676–82.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. La Vecchia C,
    2. Altieri A,
    3. Franceschi S,
    4. Tavani A
    . Oral contraceptives and cancer: an update. Drug Saf 2001;24:741–54.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Gillum LA,
    2. Mamidipudi SK,
    3. Johnston SC
    . Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA 2000;284:72–8.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Gillum LA,
    2. Mamidipudi SK,
    3. Johnston SC
    . Review: current oral contraceptive use increases the risk for ischaemic stroke. Evidence-Based Med 2001;6:60.
    OpenUrlFREE Full Text
  10. 10.↵
    Anonymous. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1995;346:1575–82.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Bosetti C,
    2. Bravi F,
    3. Negri E,
    4. La Vecchia C
    . Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis. Hum Reprod Update 2009;15:489–98.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    Anonymous. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1996;347:1713–27.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Smith JS,
    2. Green J,
    3. Berrington de Gonzalez A,
    4. Appleby P,
    5. Peto J,
    6. Plummer M,
    7. et al.
    Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003;361:1159–67.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Cibula D,
    2. Gompel A,
    3. Mueck AO,
    4. La Vecchia C,
    5. Hannaford PC,
    6. Skouby SO,
    7. et al.
    Hormonal contraception and risk of cancer. Hum Reprod Update 2010;16:631–50.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. Cibula D,
    2. Zikan M,
    3. Dusek L,
    4. Majek O
    . Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis. Expert Rev Anticancer Ther 2011;11:1197–207.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Marchbanks PA,
    2. McDonald JA,
    3. Wilson HG,
    4. Folger SG,
    5. Mandel MG,
    6. Daling JR,
    7. et al.
    Oral contraceptives and the risk of breast cancer. N Engl J Med 2002;346:2025–32.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Dolle JM,
    2. Daling JR,
    3. White E,
    4. Brinton LA,
    5. Doody DR,
    6. Porter PL,
    7. et al.
    Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev 2009;18:1157–66.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Mueck AO,
    2. Seeger H,
    3. Rabe T
    . Hormonal contraception and risk of endometrial cancer: a systematic review. Endocr Relat Cancer 2010;17:R263–71.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Beral V,
    2. Doll R,
    3. Hermon C,
    4. Peto R,
    5. 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.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Havrilesky LJ,
    2. Gierisch JM,
    3. Moorman PG,
    4. Coeytaux RR,
    5. Peragallo Urrutia R,
    6. Lowery WJ,
    7. et al.
    Oral contraceptive use for the primary prevention of ovarian cancer. Evidence Report #101. (Prepared by the Duke Evidence-based Practice Center under Contract No. 290-2007-10066-I.) AHRQ Publication No. 13-EHC033-EF. Rockville, MD: Agency for Healthcare Research and Quality. Available from: http://www.effectivehealthcare.ahrq.gov/ehc/products/416/1528/cancer-ovarian-contraceptives-report-130607.pdf.
  21. 21.↵
    1. Moorman PG,
    2. Calingaert B,
    3. Palmieri RT,
    4. Iversen ES,
    5. Bentley RC,
    6. Halabi S,
    7. et al.
    Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women. Am J Epidemiol 2008;167:1059–69.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    Agency for Healthcare Research and Quality. Methods guide for effectiveness and comparative effectiveness reviews. AHRQ Publication No. 10(12)-EHC063-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2012. Available from: www.effectivehealthcare.ahrq.gov.
  23. 23.↵
    1. Borenstein M,
    2. Hedges L,
    3. Higgins J,
    4. Rothstein H
    . Comprehensive Meta-analysis Version 2. Englewood, NJ: Biostat; 2005.
  24. 24.↵
    National Cancer Institute. Surveillance Research–Cancer Control and Population Sciences. DevCan: Probability of Developing or Dying of Cancer. [cited 2013 Jan 3]; Available from: http://surveillance.cancer.gov/devcan/.
  25. 25.↵
    Centers for Disease Control and Prevention. National Survey of Family Growth. 2006–2010 NSFG: Public Use Data Files, Codebooks, and Documentation. [cited 2013 Jan 3]; Available from: http://www.cdc.gov/nchs/nsfg/nsfg_2006_2010_puf.htm.
  26. 26.↵
    1. Owens DK,
    2. Lohr KN,
    3. Atkins D,
    4. Treadwell JR,
    5. Reston JT,
    6. Bass EB,
    7. et al.
    AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—Agency for Healthcare Research and Quality and the Effective Health-Care Program. J Clin Epidemiol 2010;63:513–23.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Shapiro S,
    2. Rosenberg L,
    3. Hoffman M,
    4. Truter H,
    5. Cooper D,
    6. Rao S,
    7. et al.
    Risk of breast cancer in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen contraceptives. Am J Epidemiol 2000;151:396–403.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Van Hoften C,
    2. Burger H,
    3. Peeters PH,
    4. Grobbee DE,
    5. Van Noord PA,
    6. Leufkens HG
    . Long-term oral contraceptive use increases breast cancer risk in women over 55 years of age: the DOM cohort. Int J Cancer 2000;87:591–4.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Gomes AL,
    2. Guimaraes MD,
    3. Gomes CC,
    4. Chaves IG,
    5. Gobbi H,
    6. Camargos AF
    . Risk factors for breast cancer among pre- or post-menopausal women in Belo Horizonte, Brazil. Gynecol Obstet Invest 2001;52:173–9.
    OpenUrlPubMed
  30. 30.↵
    1. Moorman PG,
    2. Millikan RC,
    3. Newman B
    . Oral contraceptives and breast cancer among African-American women and white women. J Natl Med Assoc 2001;93:329–34.
    OpenUrlPubMed
  31. 31.↵
    1. Heimdal K,
    2. Skovlund E,
    3. Moller P
    . Oral contraceptives and risk of familial breast cancer. Cancer Detect Prev 2002;26:23–7.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Narod SA,
    2. Dube MP,
    3. Klijn J,
    4. Lubinski J,
    5. Lynch HT,
    6. Ghadirian P,
    7. et al.
    Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2002;94:1773–9.
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    1. Althuis MD,
    2. Brogan DD,
    3. Coates RJ,
    4. Daling JR,
    5. Gammon MD,
    6. Malone KE,
    7. et al.
    Breast cancers among very young premenopausal women (United States). Cancer Causes Control 2003;14:151–60.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Althuis MD,
    2. Brogan DR,
    3. Coates RJ,
    4. Daling JR,
    5. Gammon MD,
    6. Malone KE,
    7. et al.
    Hormonal content and potency of oral contraceptives and breast cancer risk among young women. Br J Cancer 2003;88:50–7.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Newcomer LM,
    2. Newcomb PA,
    3. Trentham-Dietz A,
    4. Longnecker MP,
    5. Greenberg ER
    . Oral contraceptive use and risk of breast cancer by histologic type. Int J Cancer 2003;106:961–4.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Norman SA,
    2. Berlin JA,
    3. Weber AL,
    4. Strom BL,
    5. Daling JR,
    6. Weiss LK,
    7. et al.
    Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women. Cancer Causes Control 2003;14:933–43.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Suter NM,
    2. Malone KE,
    3. Daling JR,
    4. Doody DR,
    5. Ostrander EA
    . Androgen receptor (CAG)n and (GGC)n polymorphisms and breast cancer risk in a population-based case-control study of young women. Cancer Epidemiol Biomarkers Prev 2003;12:127–35.
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    1. Fowke JH,
    2. Shu XO,
    3. Dai Q,
    4. Jin F,
    5. Cai Q,
    6. Gao YT,
    7. et al.
    Oral contraceptive use and breast cancer risk: modification by NAD(P)H:quinone oxoreductase (NQO1) genetic polymorphisms. Cancer Epidemiol Biomarkers Prev 2004;13:1308–15.
    OpenUrlAbstract/FREE Full Text
  39. 39.↵
    1. Jernstrom H,
    2. Loman N,
    3. Johannsson OT,
    4. Borg A,
    5. Olsson H
    . Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing. Eur J Cancer 2005;41:2312–20.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Milne RL,
    2. Knight JA,
    3. John EM,
    4. Dite GS,
    5. Balbuena R,
    6. Ziogas A,
    7. et al.
    Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 2005;14:350–6.
    OpenUrlAbstract/FREE Full Text
  41. 41.↵
    1. Gronwald J,
    2. Byrski T,
    3. Huzarski T,
    4. Cybulski C,
    5. Sun P,
    6. Tulman A,
    7. et al.
    Influence of selected lifestyle factors on breast and ovarian cancer risk in BRCA1 mutation carriers from Poland. Breast Cancer Res Treat 2006;95:105–9.
    OpenUrlCrossRefPubMed
  42. 42.↵
    1. Haile RW,
    2. Thomas DC,
    3. McGuire V,
    4. Felberg A,
    5. John EM,
    6. Milne RL,
    7. et al.
    BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 2006;15:1863–70.
    OpenUrlAbstract/FREE Full Text
  43. 43.↵
    1. Rosenberg LU,
    2. Magnusson C,
    3. Lindstrom E,
    4. Wedren S,
    5. Hall P,
    6. Dickman PW
    . Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study. Breast Cancer Res 2006;8:R11.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Ma H,
    2. Bernstein L,
    3. Ross RK,
    4. Ursin G
    . Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case-control and a case-case comparison. Breast Cancer Res 2006;8:R39.
  45. 45.↵
    1. Faheem M,
    2. Khurram M,
    3. Jafri IA,
    4. Mehmood H,
    5. Hasan Z,
    6. Iqbal GS,
    7. et al.
    Risk factors for breast cancer in patients treated at NORI Hospital, Islamabad. J Pak Med Assoc 2007;57:242–5.
    OpenUrlPubMed
  46. 46.↵
    1. Folger SG,
    2. Marchbanks PA,
    3. McDonald JA,
    4. Bernstein L,
    5. Ursin G,
    6. Berlin JA,
    7. et al.
    Risk of breast cancer associated with short-term use of oral contraceptives. Cancer Causes Control 2007;18:189–98.
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Nichols HB,
    2. Trentham-Dietz A,
    3. Egan KM,
    4. Titus-Ernstoff L,
    5. Hampton JM,
    6. Newcomb PA
    . Oral contraceptive use and risk of breast carcinoma in situ. Cancer Epidemiol Biomarkers Prev 2007;16:2262–8.
    OpenUrlAbstract/FREE Full Text
  48. 48.↵
    1. Shantakumar S,
    2. Terry MB,
    3. Paykin A,
    4. Teitelbaum SL,
    5. Britton JA,
    6. Moorman PG,
    7. et al.
    Age and menopausal effects of hormonal birth control and hormone replacement therapy in relation to breast cancer risk. Am J Epidemiol 2007;165:1187–98.
    OpenUrlAbstract/FREE Full Text
  49. 49.↵
    1. Sweeney C,
    2. Giuliano AR,
    3. Baumgartner KB,
    4. Byers T,
    5. Herrick JS,
    6. Edwards SL,
    7. et al.
    Oral, injected and implanted contraceptives and breast cancer risk among U.S. Hispanic and non-Hispanic white women. Int J Cancer 2007;121:2517–23.
    OpenUrlCrossRefPubMed
  50. 50.↵
    1. Figueiredo JC,
    2. Bernstein L,
    3. Capanu M,
    4. Malone KE,
    5. Lynch CF,
    6. Anton-Culver H,
    7. et al.
    Oral contraceptives, postmenopausal hormones, and risk of asynchronous bilateral breast cancer: the WECARE Study Group. J Clin Oncol 2008;26:1411–8.
    OpenUrlAbstract/FREE Full Text
  51. 51.↵
    1. Lee E,
    2. Ma H,
    3. McKean-Cowdin R,
    4. Van Den Berg D,
    5. Bernstein L,
    6. Henderson BE,
    7. et al.
    Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomarkers Prev 2008;17:3170–8.
    OpenUrlAbstract/FREE Full Text
  52. 52.↵
    1. Nyante SJ,
    2. Gammon MD,
    3. Malone KE,
    4. Daling JR,
    5. Brinton LA
    . The association between oral contraceptive use and lobular and ductal breast cancer in young women. Int J Cancer 2008;122:936–41.
    OpenUrlCrossRefPubMed
  53. 53.↵
    1. Rosenberg L,
    2. Zhang Y,
    3. Coogan PF,
    4. Strom BL,
    5. Palmer JR
    . A case-control study of oral contraceptive use and incident breast cancer. Am J Epidemiol 2009;169:473–9.
    OpenUrlAbstract/FREE Full Text
  54. 54.↵
    1. Phillips LS,
    2. Millikan RC,
    3. Schroeder JC,
    4. Barnholtz-Sloan JS,
    5. Levine BJ
    . Reproductive and hormonal risk factors for ductal carcinoma in situ of the breast. Cancer Epidemiol Biomarkers Prev 2009;18:1507–14.
    OpenUrlAbstract/FREE Full Text
  55. 55.↵
    1. Figueiredo JC,
    2. Haile RW,
    3. Bernstein L,
    4. Malone KE,
    5. Largent J,
    6. Langholz B,
    7. et al.
    Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study. Breast Cancer Res Treat 2010;120:175–83.
    OpenUrlCrossRefPubMed
  56. 56.↵
    1. Lumachi F,
    2. Frigo AC,
    3. Basso U,
    4. Tombolan V,
    5. Ermani M
    . Estrogen therapy and risk of breast cancer in postmenopausal women: a case-control study and results of a multivariate analysis. Menopause 2010;17:524–8.
    OpenUrlPubMed
  57. 57.↵
    1. Ma H,
    2. Wang Y,
    3. Sullivan-Halley J,
    4. Weiss L,
    5. Marchbanks PA,
    6. Spirtas R,
    7. et al.
    Use of four biomarkers to evaluate the risk of breast cancer subtypes in the women's contraceptive and reproductive experiences study. Cancer Res 2010;70:575–87.
    OpenUrlAbstract/FREE Full Text
  58. 58.↵
    1. Grabrick DM,
    2. Hartmann LC,
    3. Cerhan JR,
    4. Vierkant RA,
    5. Therneau TM,
    6. Vachon CM,
    7. et al.
    Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer. JAMA 2000;284:1791–8.
    OpenUrlCrossRefPubMed
  59. 59.↵
    1. Kumle M,
    2. Weiderpass E,
    3. Braaten T,
    4. Persson I,
    5. Adami HO,
    6. Lund E
    . Use of oral contraceptives and breast cancer risk: The Norwegian-Swedish Women's Lifestyle and Health Cohort Study. Cancer Epidemiol Biomarkers Prev 2002;11:1375–81.
    OpenUrlAbstract/FREE Full Text
  60. 60.↵
    1. Dumeaux V,
    2. Alsaker E,
    3. Lund E
    . Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study. Int J Cancer 2003;105:844–50.
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Dumeaux V,
    2. Fournier A,
    3. Lund E,
    4. Clavel-Chapelon F
    . Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women. Cancer Causes Control 2005;16:537–44.
    OpenUrlCrossRefPubMed
  62. 62.↵
    1. Silvera SA,
    2. Miller AB,
    3. Rohan TE
    . Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study. Cancer Causes Control 2005;16:1059–63.
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Vessey M,
    2. Painter R
    . Oral contraceptive use and cancer. Findings in a large cohort study, 1968–2004. Br J Cancer 2006;95:385–9.
    OpenUrlCrossRefPubMed
  64. 64.↵
    1. Brohet RM,
    2. Goldgar DE,
    3. Easton DF,
    4. Antoniou AC,
    5. Andrieu N,
    6. Chang-Claude J,
    7. et al.
    Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 2007;25:3831–6.
    OpenUrlAbstract/FREE Full Text
  65. 65.↵
    1. Hannaford PC,
    2. Selvaraj S,
    3. Elliott AM,
    4. Angus V,
    5. Iversen L,
    6. Lee AJ
    . Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. BMJ 2007;335:651.
    OpenUrlAbstract/FREE Full Text
  66. 66.↵
    1. Hannaford P,
    2. Elliott A
    . Use of exogenous hormones by women and colorectal cancer: evidence from the Royal College of General Practitioners' Oral Contraception Study. Contraception 2005;71:95–8.
    OpenUrlCrossRefPubMed
  67. 67.↵
    1. Lund E,
    2. Bakken K,
    3. Dumeaux V,
    4. Andersen V,
    5. Kumle M
    . Hormone replacement therapy and breast cancer in former users of oral contraceptives–The Norwegian Women and Cancer study. Int J Cancer 2007;121:645–8.
    OpenUrlCrossRefPubMed
  68. 68.↵
    1. Dorjgochoo T,
    2. Shu XO,
    3. Li HL,
    4. Qian HZ,
    5. Yang G,
    6. Cai H,
    7. et al.
    Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a large prospective study, from 1996 to 2006. Int J Cancer 2009;124:2442–9.
    OpenUrlCrossRefPubMed
  69. 69.↵
    1. Rosenblatt KA,
    2. Gao DL,
    3. Ray RM,
    4. Nelson ZC,
    5. Wernli KJ,
    6. Li W,
    7. et al.
    Oral contraceptives and the risk of all cancers combined and site-specific cancers in Shanghai. Cancer Causes Control 2009;20:27–34.
    OpenUrlCrossRefPubMed
  70. 70.↵
    1. Wernli KJ,
    2. Ray RM,
    3. Gao DL,
    4. De Roos AJ,
    5. Checkoway H,
    6. Thomas DB
    . Menstrual and reproductive factors in relation to risk of endometrial cancer in Chinese women. Cancer Causes Control 2006;17:949–55.
    OpenUrlPubMed
  71. 71.↵
    1. Hunter DJ,
    2. Colditz GA,
    3. Hankinson SE,
    4. Malspeis S,
    5. Spiegelman D,
    6. Chen W,
    7. et al.
    Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiol Biomarkers Prev 2010;19:2496–502.
    OpenUrlAbstract/FREE Full Text
  72. 72.↵
    1. Rosenberg L,
    2. Boggs DA,
    3. Wise LA,
    4. Adams-Campbell LL,
    5. Palmer JR
    . Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women. Cancer Epidemiol Biomarkers Prev 2010;19:2073–9.
    OpenUrlAbstract/FREE Full Text
  73. 73.↵
    1. Urban M,
    2. Banks E,
    3. Egger S,
    4. Canfell K,
    5. O'Connell D,
    6. Beral V,
    7. et al.
    Injectable and oral contraceptive use and cancers of the breast, cervix, ovary, and endometrium in black South African women: case-control study. PLoS Med 2012;9:e1001182.
    OpenUrlCrossRefPubMed
  74. 74.↵
    1. Xu WH,
    2. Shu XO,
    3. Long J,
    4. Lu W,
    5. Cai Q,
    6. Zheng Y,
    7. et al.
    Relation of FGFR2 genetic polymorphisms to the association between oral contraceptive use and the risk of breast cancer in Chinese women. Am J Epidemiol 2011;173:923–31.
    OpenUrlAbstract/FREE Full Text
  75. 75.↵
    1. Bernholtz S,
    2. Laitman Y,
    3. Kaufman B,
    4. Paluch Shimon S,
    5. Friedman E
    . Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: effects of oral contraceptive use and parental origin of mutation. Breast Cancer Res Treat 2011;129:557–563.
    OpenUrlCrossRefPubMed
  76. 76.↵
    1. Marchbanks PA,
    2. Curtis KM,
    3. Mandel MG,
    4. Wilson HG,
    5. Jeng G,
    6. Folger SG,
    7. et al.
    Oral contraceptive formulation and risk of breast cancer. Contraception 2012;85:342–350.
    OpenUrlCrossRefPubMed
  77. 77.↵
    1. Tryggvadottir L,
    2. Tulinius H,
    3. Eyfjord JE,
    4. Sigurvinsson T
    . Breast cancer risk factors and age at diagnosis: an Icelandic cohort study. Int J Cancer 2002;98:604–8.
    OpenUrlCrossRefPubMed
  78. 78.↵
    1. Wrensch M,
    2. Chew T,
    3. Farren G,
    4. Barlow J,
    5. Belli F,
    6. Clarke C,
    7. et al.
    Risk factors for breast cancer in a population with high incidence rates. Breast Cancer Res 2003;5:R88–102.
    OpenUrlCrossRefPubMed
  79. 79.↵
    1. Madeleine MM,
    2. Daling JR,
    3. Schwartz SM,
    4. Shera K,
    5. McKnight B,
    6. Carter JJ,
    7. et al.
    Human papillomavirus and long-term oral contraceptive use increase the risk of adenocarcinoma in situ of the cervix. Cancer Epidemiol Biomarkers Prev 2001;10:171–7.
    OpenUrlAbstract/FREE Full Text
  80. 80.↵
    1. Santos C,
    2. Munoz N,
    3. Klug S,
    4. Almonte M,
    5. Guerrero I,
    6. Alvarez M,
    7. et al.
    HPV types and cofactors causing cervical cancer in Peru. Br J Cancer 2001;85:966–71.
    OpenUrlCrossRefPubMed
  81. 81.↵
    1. Green J,
    2. Berrington de Gonzalez A,
    3. Sweetland S,
    4. Beral V,
    5. Chilvers C,
    6. Crossley B,
    7. et al.
    Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20–44 years: the UK National Case-Control Study of Cervical Cancer. Br J Cancer 2003;89:2078–86.
    OpenUrlCrossRefPubMed
  82. 82.↵
    1. Shapiro S,
    2. Rosenberg L,
    3. Hoffman M,
    4. Kelly JP,
    5. Cooper DD,
    6. Carrara H,
    7. et al.
    Risk of invasive cancer of the cervix in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen oral contraceptives (South Africa). Cancer Causes Control 2003;14:485–95.
    OpenUrlCrossRefPubMed
  83. 83.↵
    1. Shields TS,
    2. Brinton LA,
    3. Burk RD,
    4. Wang SS,
    5. Weinstein SJ,
    6. Ziegler RG,
    7. et al.
    A case-control study of risk factors for invasive cervical cancer among U.S. women exposed to oncogenic types of human papillomavirus. Cancer Epidemiol Biomarkers Prev 2004;13:1574–82.
    OpenUrlAbstract/FREE Full Text
  84. 84.↵
    1. Nojomi M,
    2. Modaresgilani M,
    3. Mozafari N,
    4. Erfany A
    . Cervical cancer and duration of using hormonal contraceptives. Asia-Pacific J Clin Oncol 2008;4:107–112.
    OpenUrl
  85. 85.↵
    1. Vanakankovit N,
    2. Taneepanichskul S
    . Effect of oral contraceptives on risk of cervical cancer. J Med Assoc Thai 2008;91:7–12.
    OpenUrlPubMed
  86. 86.↵
    1. Moreno V,
    2. Bosch FX,
    3. Munoz N,
    4. Meijer CJ,
    5. Shah KV,
    6. Walboomers JM,
    7. et al.
    Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002;359:1085–92.
    OpenUrlCrossRefPubMed
  87. 87.↵
    1. Hammouda D,
    2. Munoz N,
    3. Herrero R,
    4. Arslan A,
    5. Bouhadef A,
    6. Oublil M,
    7. et al.
    Cervical carcinoma in Algiers, Algeria: human papillomavirus and lifestyle risk factors. Int J Cancer 2005;113:483–9.
    OpenUrlCrossRefPubMed
  88. 88.↵
    1. Levi F,
    2. Pasche C,
    3. Lucchini F,
    4. La Vecchia C
    . Oral contraceptives and colorectal cancer. Dig Liver Dis 2003;35:85–7.
    OpenUrlCrossRefPubMed
  89. 89.↵
    1. Campbell PT,
    2. Newcomb P,
    3. Gallinger S,
    4. Cotterchio M,
    5. McLaughlin JR
    . Exogenous hormones and colorectal cancer risk in Canada: associations stratified by clinically defined familial risk of cancer. Cancer Causes Control 2007;18:723–33.
    OpenUrlCrossRefPubMed
  90. 90.↵
    1. Long MD,
    2. Martin CF,
    3. Galanko JA,
    4. Sandler RS
    . Hormone replacement therapy, oral contraceptive use, and distal large bowel cancer: a population-based case-control study. Am J Gastroenterol 2010;105:1843–50.
    OpenUrlCrossRefPubMed
  91. 91.↵
    1. Kabat GC,
    2. Miller AB,
    3. Rohan TE
    . Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women. Int J Cancer 2008;122:643–6.
    OpenUrlCrossRefPubMed
  92. 92.↵
    1. Lin J,
    2. Zhang SM,
    3. Cook NR,
    4. Manson JE,
    5. Buring JE,
    6. Lee IM
    . Oral contraceptives, reproductive factors, and risk of colorectal cancer among women in a prospective cohort study. Am J Epidemiol 2007;165:794–801.
    OpenUrlAbstract/FREE Full Text
  93. 93.↵
    1. Tsilidis KK,
    2. Allen NE,
    3. Key TJ,
    4. Bakken K,
    5. Lund E,
    6. Berrino F,
    7. et al.
    Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer 2010;103:1755–9.
    OpenUrlCrossRefPubMed
  94. 94.↵
    1. Nichols HB,
    2. Trentham-Dietz A,
    3. Hampton JM,
    4. Newcomb PA
    . Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin. Cancer Epidemiol Biomarkers Prev 2005;14:1212–8.
    OpenUrlAbstract/FREE Full Text
  95. 95.↵
    1. Rosenblatt KA,
    2. Gao DL,
    3. Ray RM,
    4. Nelson ZC,
    5. Thomas DB
    . Contraceptive methods and induced abortions and their association with the risk of colon cancer in Shanghai, China. Eur J Cancer 2004;40:590–3.
    OpenUrlCrossRefPubMed
  96. 96.↵
    1. Parslov M,
    2. Lidegaard O,
    3. Klintorp S,
    4. Pedersen B,
    5. Jonsson L,
    6. Eriksen PS,
    7. et al.
    Risk factors among young women with endometrial cancer: a Danish case-control study. Am J Obstet Gynecol 2000;182:23–9.
    OpenUrlCrossRefPubMed
  97. 97.↵
    1. Maxwell GL,
    2. Schildkraut JM,
    3. Calingaert B,
    4. Risinger JI,
    5. Dainty L,
    6. Marchbanks PA,
    7. et al.
    Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk. Gynecol Oncol 2006;103:535–40.
    OpenUrlCrossRefPubMed
  98. 98.↵
    1. Dossus L,
    2. Allen N,
    3. Kaaks R,
    4. Bakken K,
    5. Lund E,
    6. Tjonneland A,
    7. et al.
    Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2010;127:442–51.
    OpenUrlPubMed
  99. 99.↵
    1. Setiawan VW,
    2. Pike MC,
    3. Kolonel LN,
    4. Nomura AM,
    5. Goodman MT,
    6. Henderson BE
    . Racial/ethnic differences in endometrial cancer risk: the multiethnic cohort study. Am J Epidemiol 2007;165:262–70.
    OpenUrlAbstract/FREE Full Text
  100. 100.↵
    1. Tao MH,
    2. Xu WH,
    3. Zheng W,
    4. Zhang ZF,
    5. Gao YT,
    6. Ruan ZX,
    7. et al.
    Oral contraceptive and IUD use and endometrial cancer: a population-based case-control study in Shanghai, China. Int J Cancer 2006;119:2142–7.
    OpenUrlCrossRefPubMed
  101. 101.↵
    1. Havrilesky L,
    2. Moorman P,
    3. Lowery W,
    4. Gierisch J,
    5. Coeytaux R,
    6. Peragallo Urrutia R,
    7. et al.
    Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis. Obstet Gynecol 2013;122:139–47.
    OpenUrlCrossRefPubMed
  102. 102.↵
    1. Peragallo Urrutia R,
    2. Coeytaux R,
    3. McBroom A,
    4. Gierisch J,
    5. Havrilesky L,
    6. Moorman P,
    7. et al.
    Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis. Obstet Gynecol 2013;122:380–9.
    OpenUrlCrossRefPubMed
  103. 103.↵
    1. Hankinson SE,
    2. Colditz GA,
    3. Manson JE,
    4. Willett WC,
    5. Hunter DJ,
    6. Stampfer MJ,
    7. et al.
    A prospective study of oral contraceptive use and risk of breast cancer (Nurses' Health Study, United States). Cancer Causes Control 1997;8:65–72.
    OpenUrlCrossRefPubMed
  104. 104.↵
    1. Kahlenborn C,
    2. Modugno F,
    3. Potter DM,
    4. Severs WB
    . Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc 2006;81:1290–302.
    OpenUrlCrossRefPubMed
  105. 105.↵
    International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 2007;370:1609–21.
    OpenUrlCrossRefPubMed
  106. 106.↵
    1. Fernandez E,
    2. La Vecchia C,
    3. Balducci A,
    4. Chatenoud L,
    5. Franceschi S,
    6. Negri E
    . Oral contraceptives and colorectal cancer risk: a meta-analysis. Br J Cancer 2001;84:722–7.
    OpenUrlCrossRefPubMed
  107. 107.↵
    1. Grimes DA,
    2. Economy KE
    . Primary prevention of gynecologic cancers. Am J Obstet Gynecol 1995;172:227–35.
    OpenUrlCrossRefPubMed
  108. 108.↵
    1. Schlesselman JJ
    . Risk of endometrial cancer in relation to use of combined oral contraceptives. A practitioner's guide to meta-analysis. Hum Reprod 1997;12:1851–63.
    OpenUrlFREE Full Text
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Cancer Epidemiology Biomarkers & Prevention: 22 (11)
November 2013
Volume 22, Issue 11
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Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review
Jennifer M. Gierisch, Remy R. Coeytaux, Rachel Peragallo Urrutia, Laura J. Havrilesky, Patricia G. Moorman, William J. Lowery, Michaela Dinan, Amanda J. McBroom, Vic Hasselblad, Gillian D. Sanders and Evan R. Myers
Cancer Epidemiol Biomarkers Prev November 1 2013 (22) (11) 1931-1943; DOI: 10.1158/1055-9965.EPI-13-0298

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Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review
Jennifer M. Gierisch, Remy R. Coeytaux, Rachel Peragallo Urrutia, Laura J. Havrilesky, Patricia G. Moorman, William J. Lowery, Michaela Dinan, Amanda J. McBroom, Vic Hasselblad, Gillian D. Sanders and Evan R. Myers
Cancer Epidemiol Biomarkers Prev November 1 2013 (22) (11) 1931-1943; DOI: 10.1158/1055-9965.EPI-13-0298
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Cancer Epidemiology, Biomarkers & Prevention
eISSN: 1538-7755
ISSN: 1055-9965

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