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Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial
Open accessAbstract
A plausible mechanism to explain thrombotic risk differences associated with the use of second- and third-generation oral contraceptives (OCs), particularly in carriers of factor V(Leiden), is still lacking. In a double-blind trial, 51 women without and 35 women with factor V(Leiden) were randomized to either a second- (30 microg ethinylestradiol/150 microg levonorgestrel) or third- (30 microg ethinylestradiol/150 microg desogestrel) generation OC. After 2 cycles of use and a wash-out of 2 cycles, the participants continued with the corresponding progestagen-only preparation. Hemostatic variables that probe the activity of the anticoagulant protein C system were determined. Compared with levonorgestrel, desogestrel-containing OCs significantly decreased protein S and increased activated protein C (APC) resistance in both groups. OCs with desogestrel had the most pronounced effects in carriers of factor V(Leiden). Progestagen-only preparations caused changes of anticoagulant parameters opposite to those of combined OCs, which in a number of cases were more pronounced with levonorgestrel. Our data show that progestagens in combined OCs counteract the thrombotic effect of the estrogen component. The higher thrombotic risk associated with third-generation OCs compared with second-generation OCs may be explained by the fact that desogestrel appeared less antithrombotic than levonorgestrel, especially in women with factor V(Leiden).
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“In contrast, the credibility of much debated epidemiologic findings of a difference in thrombosis risk between different types of oral contraceptives was greatly enhanced by the differences in coagulation found in a randomised cross-over trial [ 214 ].”
From Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration (2007) · cites this paper as [214]
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“Simultaneously, a pronounced decrease in levels of Protein S antigen (total and free) has been noted with CHC use, more significantly with use of 3rd generation progesterone containing CHCs[63, 65, 66] and in post-menopausal women [64].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [65]
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“In contrast, the credibility of much debated epidemiologic findings of a difference in thrombosis risk between different types of oral contraceptives was greatly enhanced by the differences in coagulation found in a randomized cross-over trial.(214) A discussion of the existing external evidence, from different types…”
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Metadata
- Authors
- Kemmeren, J. M., Algra, A., Meijers, J. C. M., Tans, G., Bouma, B. N., Curvers, J., Rosing, J., & Grobbee, D. E.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-02-01
- Volume
- 103
- Issue
- 3
- Pages
- 927-933
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2130928200
- Cited by
- 157
- References
- 41
- Citations by year
- 2025: 4 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 9 · 2014: 7 · 2013: 11 · 2012: 8
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- oral contraceptives, factor V Leiden, protein C system, protein S, activated protein C resistance, desogestrel, levonorgestrel, progestogens, thrombosis risk, ethinyl estradiol, anticoagulant activity
- MeSH terms
- Adolescent, Adult, Contraceptives, Oral, Combined, Ethinyl Estradiol, Factor V, Female, Humans, Mutation, Protein C, Risk Factors, Thrombosis, Levonorgestrel, Desogestrel
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