SynthesisFrontiers in endocrinology2024
Are natural estrogens used in contraception at lower risk of venous thromboembolism than synthetic ones? A systematic literature review and meta-analysis.
Synthesis in Frontiers in endocrinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Estetrol/drospirenone for combined oral contraception: a systematic review of efficacy, cycle control, and safety.Frontiers in endocrinology · 2026Pooled it
- Venous thromboembolism in women on estrogen therapy: presentation, management, and outcomes in the RIETE registry.Blood advances · 2026Article
- Review
- Cardiovascular Safety of Hormonal Contraception: Method-Specific Risks and Clinical Implications.Medical sciences (Basel, Switzerland) · 2026Review
- Medical Treatment for Endometriosis: One Size Does Not Fit All.Journal of clinical medicine · 2026Review
- Venous Thromboembolism Risk Associated With Relugolix-estradiol-norethisterone Acetate Combination Therapy.Journal of the Endocrine Society · 2026Review
- Body-identical estrogens in combined hormonal contraceptives: A safer path forward.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Article
- Predicting venous thromboembolism risk from endogenous thrombin potential-based normalized activated protein C sensitivity ratio assay: toward early assessment of combined oral contraceptives.Research and practice in thrombosis and haemostasis · 2026Article
- A detailed review of pharmacokinetics/pharmacodynamics of progestogens in oral contraception.Frontiers in endocrinology · 2026Review
- Position Statement on Cardiometabolic Health Across the Woman's Life Course - 2025.Arquivos brasileiros de cardiologia · 2025Article
- Combined Oral Contraceptives and the Risk of Thrombosis.International journal of molecular sciences · 2025Review
- The impact of protein S and tissue factor pathway inhibitor on coagulation, assessed with thrombin generation, in women starting combined oral contraceptives.Research and practice in thrombosis and haemostasis · 2025Article
- The effect of combined oral contraceptives on thrombin generation assessed on ST Genesia- a paired clinical study.Thrombosis journal · 2025Article
- Commentary: The ETP-based APC resistance assay remains the gold standard for evaluating the APC resistance phenotype in users of combined oral contraceptives.Frontiers in cardiovascular medicine · 2025Article
- Chapter 3. Impact of estrogens on hemostasis.Frontiers in endocrinology · 2025Review
- Anamnesis Checklist for Informed Oral Contraceptive Choices: A Spanish Perspective.Women's health reports (New Rochelle, N.Y.) · 2025Article
- Position Statement on Cardiometabolic Health Across the Woman's Life Course - 2025.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2025Article
- Hormonal Therapies for Acne: A Comprehensive Update for Dermatologists.Dermatology and therapy · 2025Review
- Cost-effective screening strategy to prevent venous thromboembolism in combined oral contraceptive users.Frontiers in endocrinology · 2025Article
- Reassessing the Risk of Venous Thromboembolism (VTE) Events in Women.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisReview
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: 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). Methods: 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. Results: 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. Discussion and conclusion: 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.
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