ReviewFrontiers in endocrinology2021
Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk.
Review in Frontiers in endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 3 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Estetrol-based combined oral contraceptives: A systematic review of clinical outcomes.Acta obstetricia et gynecologica Scandinavica · 2026Pooled it
- Efficacy and safety of therapeutic exercise for primary dysmenorrhea: a systematic review and meta-analysis.Frontiers in medicine · 2025Pooled it
- Are natural estrogens used in contraception at lower risk of venous thromboembolism than synthetic ones? A systematic literature review and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Safety and Efficacy of a 24-Cycle Administration of a Drospirenone-Only Pill in Japanese Women.The journal of obstetrics and gynaecology research · 2026Trial
- High Altitude Pulmonary Edema Response to Continuous Airway Positive Pressure: A Randomized Controlled Trial: The HAPER CAPER Trial.Academic emergency medicine : official journal of the Society for Academic Emergency Medicine · 2025Trial
- Efficacy and safety of drospirenone as a progestin-only pill in Japanese women: A phase III study.The journal of obstetrics and gynaecology research · 2025Trial
- Impact of Estetrol Combined with Drospirenone on Blood Coagulation and Fibrinolysis in Patients with Endometriosis: A Multicenter, Randomized, Open-Label, Active-Controlled, Parallel-Group Study.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisTrial
- Impact of estroprogestin therapies on bone health from adolescence to postmenopause.Journal of endocrinological investigation · 2026Review
- Venous thromboembolism in women on estrogen therapy: presentation, management, and outcomes in the RIETE registry.Blood advances · 2026Article
- Treatment selection for adenomyosis based on imaging findings and patient characteristics.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Review
- Venous Thromboembolism in Transgender and Gender Diverse Individuals on Estrogen-Based Gender-Affirming Hormone Therapy.Journal of clinical medicine · 2026Article
- Prescribed hormonal contraceptive use trends in the Estonian Biobank: A longitudinal observational study.PLoS medicine · 2026Observational
- Current Body Mass Index Is Associated with Reported Weight Gain as a Reason for Discontinuing Oral Contraceptive Pill Use.Obesities · 2026Article
- Medical Treatment for Endometriosis: One Size Does Not Fit All.Journal of clinical medicine · 2026Review
- Cardiovascular risk profile according to World Health Organization medical eligibility criteria for contraceptive use of women using hormonal contraception in Rio de Janeiro state, Brazil.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Article
- Venous Thromboembolism Risk Associated With Relugolix-estradiol-norethisterone Acetate Combination Therapy.Journal of the Endocrine Society · 2026Review
- 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
- Prothrombin conversion accelerates with increasing age in women but not in men: findings from the Moli-sani Cohort Study.Research and practice in thrombosis and haemostasis · 2026Article
- Editorial: Recent advances in thromboembolism and oral contraceptives.Frontiers in endocrinology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many factors must be considered and discussed with women when initiating a contraceptive method and the risk of venous thromboembolism (VTE) is one of them. In this review, we discuss the numerous strategies that have been implemented to reduce the thrombotic risk associated with combined oral contraceptives (COCs) from their arrival on the market until today. Evidences suggesting that COCs were associated with an increased risk of VTE appeared rapidly after their marketing. Identified as the main contributor of this risk, the dosage of the estrogen, i.e., ethinylestradiol (EE), was significantly reduced. New progestins were also synthetized (e.g., desogestrel or gestodene) but their weak androgenic activity did not permit to counterbalance the effect of EE as did the initial progestins such as levonorgestrel. Numerous studies assessed the impact of estroprogestative combinations on hemostasis and demonstrated that women under COC suffered from resistance towards activated protein C (APC). Subsequently, the European Medicines Agency updated its guidelines on clinical investigation of steroid contraceptives in which they recommended to assess this biological marker. In 2009, estradiol-containing COCs were marketed and the use of this natural form of estrogen was found to exert a weaker effect on the synthesis of hepatic proteins compared to EE. In this year 2021, a novel COC based on a native estrogen, i.e., estetrol, will be introduced on the market. Associated with drospirenone, this preparation demonstrated minor effects on coagulation proteins as compared with other drospirenone-containing COCs. At the present time, the standard of care when starting a contraception, consists of identifying the presence of hereditary thrombophilia solely on the basis of familial history of VTE. This strategy has however been reported as poorly predictive of hereditary thrombophilia. One rationale and affordable perspective which has already been considered in the past could be the implementation of a baseline screening of the prothrombotic state to provide health care professionals with objective data to support the prescription of the more appropriate contraceptive method. While this strategy was judged too expensive due to limited laboratory solutions, the endogenous thrombin potential-based APC resistance assay could now represent an interesting alternative.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.