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Review
. 2023 Nov 28;15(23):5624.
doi: 10.3390/cancers15235624.

Hormonal Contraception and the Risk of Breast Cancer in Women of Reproductive Age: A Meta-Analysis

Luz Angela Torres-de la Roche  1 , Angélica Acevedo-Mesa  1 , Ingrid Lizeth Lizarazo  1 , Rajesh Devassy  1 , Sven Becker  2 , Harald Krentel  3 , Rudy Leon De Wilde  1
Affiliations
Review

Hormonal Contraception and the Risk of Breast Cancer in Women of Reproductive Age: A Meta-Analysis

Luz Angela Torres-de la Roche et al. Cancers (Basel). .

Abstract

This study aims to summarize evidence from observational studies about the lifetime use of HC and the risk of BC in women of reproductive age. The PubMed, Cochrane, and EMBASE databases were searched for observational studies published from 2015 to February 2022. Meta-analyses were performed using adjusted odds ratios and relative risks with a random-effects model using the I2 statistic to quantify the heterogeneity among studies. Of the 724 studies identified, 650 were screened for title/abstract selection, 60 were selected for full-text revision, and 22 were included in the meta-analysis. Of these, 19 were case-control studies and 3 were cohort studies. The results of the meta-analysis indicate a significantly higher risk of developing BC in ever users of HC (pooled OR = 1.33; 95% CI = 1.19 to 1.49). This effect is larger in the subgroups of case-control studies (pooled OR = 1.44, 95% CI = 1.21 to 1.70) and in the subgroup of studies that strictly define menopausal status (pooled OR = 1.48; 95% CI, 1.10 to 2.00). Although our meta-analysis of observational studies (cohort and case-control) suggests a significantly increased overall risk of BC in users or ever-users of modern hormonal contraceptives, the high heterogeneity among studies (>70%) related to differences in study design, measurement of variables, confounders, among other factors, as well as publication biases should be considered when interpreting our results.

Keywords: breast cancer; hormonal contraception; meta-analysis; premenopausal; risk factors.

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Conflict of interest statement

The authors declare that they have no known competing financial interest or personal relationships that could appear to influence the work reported in this paper.

Figures

Figure A1
Figure A1
Risk of bias criteria for studies included in the analyses according to the Newcastle-Ottawa Quality Assessment Scale.
Figure A2
Figure A2
Funnel plot of the comparison relating to Hormonal Contraceptive Use (HC) and the Risk of Breast Cancer (BC) across all studies included in this metanalysis.
Figure 1
Figure 1
Flow diagram of the selection process for studies included in this meta-analysis: hormonal contraceptive use as a potential risk factor for breast cancer. The reasons for exclusion were as follows: (A) not the intended outcome—e.g., the study outcome was mortality rate but not risk of BC; (B) not the intended exposure—e.g., hormone replacement therapy; (C) not the intended participant—e.g., males, cancer survivors, women with a family history of BC, or underage or post-menopausal women; (D) not the intended study design or not an observational study; (E) not an original research study—e.g., book chapters, abstracts, or other meta-analyses; (F) not quantitative data reported—e.g., odds ratios, risk ratios, or hazard ratios; and (G) studies focusing exclusively on BC subtypes.
Figure 2
Figure 2
Percentage of risk of bias for studies included in the analysis, according to the Newcastle-Ottawa Quality Assessment Scale [20].
Figure 3
Figure 3
Hormonal contraceptive use and the risk of breast cancer in adult women according to case-control and cohort studies included in the analysis.
Figure 4
Figure 4
Subgroup analysis of hormonal contraceptive use and the risk of breast cancer between groups of case-control and cohort studies distinguished by menopausal status.
Figure 5
Figure 5
Subgroup analysis of hormonal contraceptive use and the risk of breast cancer between groups of cohort and case-control studies.
See this image and copyright information in PMC

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