Oral contraceptives and risk of endometriosis: a systematic review and meta-analysis
Abstract
BACKGROUND: Combined oral contraceptives (OCs) inhibit ovulation, substantially reduce the volume of menstrual flow and may hypothetically interfere with implantation of refluxed endometrial cells. The aim of this review is to establish if OC use influences the risk of endometriosis. METHODS: We performed a MEDLINE search to identify all studies published in the last four decades (January 1970 to January 2010) in the English language on the relationship between OC exposure and risk of endometriosis. Two authors abstracted data on standardized forms. RESULTS: We identified 608 potentially relevant studies and 18 studies (6 cross-sectional, 7 case-control and 5 cohort) were selected. Pooling of the results derived from all the included reports independently from study design, yielded a common relative risk of 0.63 [95% confidence interval (CI), 0.47-0.85] for current OC users, 1.21 (95% CI, 0.94-1.56) for past users and 1.19 (95% CI, 0.89-1.60) for ever users. Methodological drawbacks, such as uncertain temporal relationship between exposure and outcome in cross-sectional studies and suboptimal selection of controls in case-control studies, limit the quality of the available evidence. CONCLUSIONS: The risk of endometriosis appears reduced during OC use. However, it is not possible to exclude the possibility that the apparent protective effect of OC against endometriosis is the result of postponement of surgical evaluation due to temporary suppression of pain symptoms. Confounding by selection and indication biases may explain the trend towards an increase in risk of endometriosis observed after discontinuation, but further clarification is needed. To date, the hypothesis of recommending OCs for primary prevention of endometriosis does not seem sufficiently substantiated.
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The usefulness of hormonal contraceptives for the primary prevention of endometriosis is uncertain.
“The usefulness of hormonal contraceptives for the primary prevention of endometriosis is uncertain (Vercellini et al., 2011).”
From ESHRE guideline: endometriosis (2022) · cites this paper as Vercellini et al., 2011
The Discussion (p. 10) says the evidence is not yet clear enough to suggest oral contraceptives for primary prevention of endometriosis, and the conclusions (p. 1) call that recommendation insufficiently substantiated. The citing sentence broadens this finding from oral contraceptives to hormonal contraceptives generally, which the paper does not assess. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPast users of COCs have an increased risk of endometriosis.
“Studies also showed an increased risk of endometriosis in past users of COCs [251].”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [251]
An increased risk of endometriosis was observed in past users of OCPs.
“an increased risk of the disease was observed in past users of OCPs [72,73]”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [73]
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- Authors
- Vercellini, P., Eskenazi, B., Consonni, D., Somigliana, E., Parazzini, F., Abbiati, A., & Fedele, L.
- Affiliations
- University of Milan (IT)
- University of California, Berkeley (US)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Corresponding author
- Vercellini, P.
- Venue
- Human Reproduction Update
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-09-10
- Volume
- 17
- Issue
- 2
- Pages
- 159-170
- ISSN
- 1355-4786 (ISSN-L)
- 1460-2369
- OpenAlex
- W2098330734
- Cited by
- 176
- References
- 55
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 14 · 2018: 10 · 2017: 13 · 2016: 12 · 2015: 11 · 2014: 11 · 2013: 10 · 2012: 10
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction Update (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Keywords
- oral contraceptives, endometriosis, combined oral contraceptives, endometriosis risk, ovulation inhibition, endometrial implantation, primary prevention, selection bias, confounding by indication
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Contraceptives, Oral, Cross-Sectional Studies, Endometriosis, Female, Humans, Middle Aged, Cohort Studies, Case-Control Studies, Risk Assessment
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