Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives
Abstract
Epidemiological studies have shown that women who use third-generation oral contraceptives (OC) containing desogestrel, gestodene or norgestimate have a higher risk of venous thrombosis than women who use second-generation OC containing levonorgestrel. It is also known that a mutation in factor V (factor V(Leiden)), which results in resistance to activated protein C (APC) and which is the most common cause of hereditary thrombophilia, potentiates the prothrombotic effect of OC. Effects of APC on thrombin generation in the plasma of women using OC were compared to the response to APC in non-OC users and in individuals that were heterozygous or homozygous for factor V(Leiden). The response towards APC was evaluated on basis of the ratio (APC-sr) of the time integrals of thrombin formation determined in the presence and absence of APC. Compared with women not using OC, women who used OC exhibited a significantly decreased sensitivity to APC (P<0.001), independent of the kind of OC used. Women who used third-generation monophasic OC were significantly less sensitive to APC than women using second-generation OC (P<0.001) and had APC-sr that did not significantly differ from heterozygous female carriers of factor V(Leiden) who did not use OC. Women who were heterozygous for factor V(Leiden) and used OC had APC-sr in the range of homozygous carriers of factor V(Leiden). Two women who started OC therapy had significantly elevated APC-sr within 3 d. Acquired APC resistance may explain the epidemiological observation of increased risk for venous thrombosis in OC users, especially in women using third-generation OC.
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CHC users have significantly higher APC resistance compared to non-CHC users.
“Thus, CHC users are noted to have significantly higher APC resistance, when compared to non CHC users [81].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [81]
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- Authors
- Rosing, J., Tans, G., Nicolaes, G. A. F., Thomassen, M. C. L. G. D., Van Oerle, R., Van DerPloeg, P. M. E. N., Heijnen, P., Hamulyak, K., & Hemker, H. C.
- Affiliations
- Maastricht University Medical Centre (NL)
- Corresponding author
- Rosing, J.
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 1997-04
- Volume
- 97
- Issue
- 1
- Pages
- 233-238
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W2026785440
- Cited by
- 325
- References
- 24
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 8
- FWCI
- 18.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- 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, venous thrombosis, activated protein C resistance, factor V Leiden, thrombophilia, third-generation oral contraceptives, second-generation oral contraceptives, desogestrel, gestodene, norgestimate, levonorgestrel, thrombin generation
- MeSH terms
- Adolescent, Adult, Aged, Contraceptives, Oral, Combined, Factor V, Female, Hemostasis, Heterozygote, Humans, Male, Middle Aged, Norgestrel, Norpregnenes, Protein C, Thrombin, Thrombophlebitis, Levonorgestrel, Desogestrel
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