Oral contraceptives and risk of endometriosis: A systematic review and meta-analysis

Paolo Vercellini, Brenda Eskenazi, Dario Consonni, Edgardo Somigliana, Fabio Parazzini, Annalisa Abbiati, Luigi Fedele

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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.

Original languageEnglish
Article numberdmq042
Pages (from-to)159-170
Number of pages12
JournalHuman Reproduction Update
Issue number2
Publication statusPublished - Mar 2011


  • Endometriosis
  • Meta-analysis
  • Observational studies
  • Oral contraceptives
  • Systematic review

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine


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