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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1428597
This article is part of the Research Topic Recent Advances in Thromboembolism and Oral Contraceptives View all articles

Are natural estrogens used in contraception at lower risk of venous thromboembolism than synthetic ones? A systematic literature review and meta-analysis

Provisionally accepted
Jonathan Douxfils Jonathan Douxfils 1,2*Lucie Raskin Lucie Raskin 1Marie Didembourg Marie Didembourg 1Nathalie Donis Nathalie Donis 2Jean-Michel Dogné Jean-Michel Dogné 1Laure Morimont Laure Morimont 1,2Charlotte Beaudart Charlotte Beaudart 1
  • 1 University of Namur, Namur, Belgium
  • 2 Qualiblood s.a., Namur, Belgium

The final, formatted version of the article will be published soon.

    Venous thromboembolism (VTE) poses a significant global health challenge, notably exacerbated by the use of combined oral contraceptives (COCs). Evidence mainly focuses on the type of progestogen used in COCs to establish the increased risk of VTE with less data assessed on the type of estrogen used. This meta-analysis aims to assess the risk of VTE associated with COCs containing synthetic estrogens like ethinylestradiol (EE) versus natural estrogens like estradiol (E2).A systematic review and meta-analysis was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were performed in December 2023 in MEDLINE and EMBASE to identify clinical studies comparing the VTE risk between COCs containing synthetic versus natural estrogens. Studies were selected through rigorous screening, and data extraction followed standardized protocols, with statistical analyses employing a random effects model.The search yielded five relevant studies, involving over 560,000 women/time, demonstrating a significant 33% reduction in VTE risk among users of natural estrogen-based COCs compared to synthetic estrogen-based COCs (OR 0.67, 95% CI 0.51-0.87). Stratification analyses using adjusted hazard ratios (HR) of the main observationnal studies showed a 49% reduced VTE risk of E2-based pills compared to EE in association with levonorgestrel.Despite the longstanding use of EE-based COCs, emerging evidence supports a lower thrombotic risk associated with natural estrogens. This meta-analysis substantiates the lower VTE risk associated with natural estrogen-based COCs compared to synthetic alternatives, advocating for a re-evaluation of contraceptive guidelines to prioritize patient safety and reduce thrombotic risks.

    Keywords: Meta-analysis, Combined oral contraceptive, Estradiol, ethinylestradiol, Venous Thromboembolism

    Received: 06 May 2024; Accepted: 09 Jul 2024.

    Copyright: © 2024 Douxfils, Raskin, Didembourg, Donis, Dogné, Morimont and Beaudart. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jonathan Douxfils, University of Namur, Namur, Belgium

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