The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
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).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Vandenbroucke, J. P., Koster, T., Rosendaal, F. R., Briët, E., Reitsma, P. H., & Bertina, R. M. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90286-0 · Cited by 1,063
Jick, H., Jick, S. S., Myers, M. W., Vasilakis‐Scaramozza, C., & Gurewich, V. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91928-7 · Cited by 721
Inman, W. H. W., Vessey, M. P., Westerholm, B., & Engelund, A. (1970) · BMJ · doi:10.1136/bmj.2.5703.203 · Cited by 609
Spitzer, W. O., Lewis, M. A., Heinemann, L. A. J., Thorogood, M., & MacRae, K. D. (1996) · BMJ · doi:10.1136/bmj.312.7023.83 · Cited by 590
Bloemenkamp, K. W. M., Helmerhorst, F. M., Rosendaal, F. R., Vandenbroucke, J. P., & Buller, H. R. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91929-5 · Cited by 576
Recurrent Venous Thromboembolism in Patients with a Partial Deficiency of Protein S
Comp, P. C., & Esmon, C. T. (1984) · New England Journal of Medicine · doi:10.1056/nejm198412133112401 · Cited by 498
Oral Contraceptives and Cardiovascular Disease
Stadel, B. V. (1981) · New England Journal of Medicine · doi:10.1056/nejm198109103051104 · Cited by 494
World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception (1995) · The Lancet · doi:10.1016/s0140-6736(95)91927-9 · Cited by 453
Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V
Voorberg, J., Roelse, J., Mertens, K., van MOURIK, J. A., Koopman, R., Buller, H. R., Berends, F. J., & ten Cate, J. W. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92939-4 · Cited by 426
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. (1997) · British Journal of Haematology · doi:10.1046/j.1365-2141.1997.192707.x · Cited by 325
Self-citation
Cited by
Sorted by citations
Items 101–156 of 156
Progestin isoforms provide different levels of protein S expression in HepG2 cells
Kozuka, T., Tamura, S., Kawamura, N., Nakata, Y., Hasebe, R., Makiyama, A., Takagi, Y., Murata, M., Mizutani, N., Takagi, A., et al. (2016) · Thrombosis Research · doi:10.1016/j.thromres.2016.07.007 · Cited by 6
Urbaniak, J., Zielińska‐Bliźniewska, H., Miłoński, J., Pietkiewicz, P., Kuśmierczyk, K., & Olszewski, J. (2013) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-013-2853-x · Cited by 5
Semi-automated thrombin dynamics applying the ST Genesia thrombin generation assay
Carlo, A., Yan, Q., Cate, H. T., Kremers, R., de Laat, B., & Ninivaggi, M. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.912433 · Cited by 5
Clinical Trials in Pharmacogenomics and Stratified Medicine
Padmanabhan, S. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-386882-4.00015-3 · Cited by 4
Hemorheological mechanisms for increased thrombosis in subjects using gestodene
Swanepoel, A. C., Roberts, H. C., Soma, P., Lindeque, B. G., & Bester, J. (2018) · Microscopy Research and Technique · doi:10.1002/jemt.23149 · Cited by 4
Mise au point sur la contraception progestative
Madélénat, P., & Koskas, M. (2009) · Sages-Femmes · doi:10.1016/j.sagf.2008.06.001 · Cited by 4
Yu, X., Yaman, M., Zhao, Q. Y., Emly, S. M., Lee, J. K., Su, H., Ferguson, A. C., Nagaswami, C., Chaturantabut, S., Goessling, W., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.13.623199 · Cited by 4
Ninivaggi, M., Sokolova, L., Donkervoort, D., de Laat, B., & Kremers, R. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1490601 · Cited by 3
Oral Contraception and Thrombophilia
Blickstein, D., & Blickstein, I. (2008) · Postgraduate Obstetrics & Gynecology · doi:10.1097/01.pgo.0000316647.92408.1b · Cited by 3
Activation of coagulation system during air travel
Bertoni, G. B., & Rampoldi, V. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68959-9 · Cited by 3
Commentary: Maziak's essay, seen from another angle
Vandenbroucke, J. P. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dyn267 · Cited by 3
Role of tissue factor pathway inhibitor in hormone-induced venous thromboembolism
Arafat, A., Gennari, P., Ignatov, A., & Tchaikovski, S. N. (2023) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000001198 · Cited by 2
Increased resistance to activated protein C in women taking third-generation oral contraceptives?
Gris, J., Nouvellon-Cochery, E., & Marès, P. (2004) · Blood · doi:10.1182/blood-2004-01-0101 · Cited by 2
Hsu, P.-J., Chen, C.-H., & Lin, S.-K. (2025) · Journal of Nippon Medical School · doi:10.1272/jnms.jnms.2025_92-605 · Cited by 1
Anticoagulation for Proximal Deep Vein Thrombosis
Lee, A. I., & Lee, E. (2017) · Springer eBooks · doi:10.1007/978-3-319-65226-9_23 · Cited by 1
Contraception in women with obesity with special reference to gastric bypass surgery
Ginstman, C. (2019) · Linköping University medical dissertations · doi:10.3384/diss.diva-156643 · Cited by 1
Shoupe, D., & Mishell, D. R. (2006) · Humana Press eBooks · doi:10.1007/978-1-59745-150-5_2 · Cited by 1
Agarwal, T., Mereuta, O. M., Ghozy, S. A., Larco, J. A., Bilgin, C., Kadirvel, R., Brinjikji, W., & Kallmes, D. F. (2024) · BMC Neurology · doi:10.1186/s12883-024-03579-2 · Cited by 1
Aortic thrombus with contraceptive vaginal ring use
Smith, K. L., Bolton, K., Weger, N. S., & Hobbs, R. A. (2023) · Journal of Pharmacy Practice and Research · doi:10.1002/jppr.1856 · Cited by 1
Serfaty, D. (2011) · Elsevier eBooks · doi:10.1016/b978-2-294-70921-0.00006-1 · Cited by 1
Venous thromboembolism in women : risk factors and long term follow-up
Sonnevi, K. (2013) · Figshare · Cited by 1
Avaliação do efeito de contraceptivos hormonais sobre a hemostasia
Stocco, B. (2011) · doi:10.11606/d.60.2011.tde-29092011-091830 · Cited by 1
Hormone-induced changes in the coagulation system
Tchaikovski, S. N. (2009) · doi:10.26481/dis.20091216st · Cited by 1
Combined Estrogen–Progestin Oral Contraceptives
Martinelli, I., Battaglioli, T., & Mannucci, P. M. (2004) · New England Journal of Medicine · doi:10.1056/nejm200401153500322 · Cited by 1
Molecular Pharmacoepidemiology
Kimmel, S. E., Leufkens, H. G. M., & Rebbeck, T. R. (2012) · Pharmacoepidemiology · doi:10.1002/9781119959946.ch34 · Cited by 1
Gender Issues in Venous Thromboembolism
Murin, S., Bilello, K. L., Moores, L. K., & Holley, A. B. (2010) · Principles of Gender-Specific Medicine · doi:10.1016/b978-0-12-374271-1.00020-4
5B.2 Mechanism of hormonal therapy related thrombosis
Tchaikovski, S. N., Tans, G., & Rosing, J. (2007) · Thrombosis Research · doi:10.1016/s0049-3848(07)70032-4
Self-citationSeguimiento de los valores de antitrombina en mujeres en tratamiento anticonceptivo oral
Franco, C. A. (2004) · Atención Primaria · doi:10.1016/s0212-6567(04)79541-4
Translating pharmacogenetics to primary care
Swen, J. J. (2011) · Leiden Repository (Leiden University)
Cardiovascular Risk Biomarkers among Oral and Vaginal Hormonal Contraceptive Users
Brandy, K. R. (2011) · University of Minnesota Digital Conservancy (University of Minnesota)
Risque de thrombose sous contraceptifs oraux : pharmacovigilance au CHU de Grenoble
Jorioz, C. (2014) · HAL
EL EQUILIBRIO HEMOSTÁTICO, UN PROCESO COMPLEJO
García, Y. D. I. (2016)
Enquête étiologique au cours de la maladie veineuse thromboembolique
Delluc, A., Gal, G. L., & Mottier, D. (2010) · Encyclopédie médico-chirurgicale. Pneumologie · doi:10.1016/s1155-195x(10)47974-8
Thrombotic Risk of Contraceptives and Other Hormonal Therapies
Sood, S. L., & Konkle, B. A. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4557-2296-9.00033-6
Adolescent Pregnancy and Contraception
Elami-Suzin, M., & Schenker, J. G. (2017) · ISGE series · doi:10.1007/978-3-319-41433-1_14
Impact of combined hormonal therapy on coagulation inhibitory proteins
Ibrahimi, E., & Koni, M. (2016) · Eastern Journal Of Medicine · doi:10.5505/ejm.2016.52388
Adolescent and Contraceptive Practices
Elami-Suzin, M., & Schenker, J. G. (2016) · International Journal of Gynecology & Clinical Practices · doi:10.15344/2394-4986/2016/117
IN TRANSLATION The Role of Endothelial Cell Injury in Thrombotic Microangiopathy
Goldberg, R. J., Nakagawa, T., Johnson, R. J., & Thurman, J. M. (2010)
Plu‐Bureau, G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.65736-7
Revista Científica FAEMA v. 09, n. 1, jan./jun. 2018
Cavalcante, E. R., & Soares, E. R. (2018) · Revista Científica FAEMA · doi:10.31072/rcf.v9i1.622
Thrombotic Risk of Contraceptives and Other Hormonal Therapies
Sood, S. L., Stein, S., & Konkle, B. A. (2007) · Elsevier eBooks · doi:10.1016/b978-141602401-9.10034-3
Typical errors pulmonary artery verification on the example of a clinical case
Vasiltseva, O. Y., Ворожцова, И. Н., Львовна, Б. И., Мильевич, Г. В., Николаевна, В. К., & Karpov, R. S. (2020) · Terapevticheskii arkhiv · doi:10.26442/00403660.2020.04.000516
Venous and Arterial Risks Associated with Combined Hormonal Contraception
Reid, J. A., & Jensen, J. T. (2021) · Trends in andrology and sexual medicine · doi:10.1007/978-3-030-70932-7_9
Oral Contraceptive Use in Obese Adolescents: A Cautionary TalePreprint
Rodriguez, V., Warad, D., & Chattha, A. J. (2020) · doi:10.22541/au.159423170.03507147
Risk of thromboembolic complications during hormone therapy
Melnikov, A. P., & Fedorenko, V. A. (2022) · Clinical Medicine (Russian Journal) · doi:10.30629/0023-2149-2022-100-1-11-17
Molecular Pharmacoepidemiology
Lu, C. Y., & Kimmel, S. E. (2019) · Pharmacoepidemiology · doi:10.1002/9781119413431.ch30
Thrombotic Risk of Contraceptives and Other Hormonal Therapies
Konkle, B. A., & Sood, S. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-46202-0.00031-5
(2004) · Journal of Women s Health · doi:10.1089/154099904323087141
The dynamics of thrombin generation
Yan, Q. (2022) · doi:10.26481/dis.20220510qy
Thrombin generation in different cohorts: Evaluation of the haemostatic potential
Chaireti, R. (2013) · Linköping University Electronic Press eBooks · doi:10.3384/diss.diva-100218
Plu‐Bureau, G. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00192-8
Women’s and Transgender Issues in Thrombosis and Hemostasis
Abdulrehman, J., Weyand, A. C., & Shehata, N. (2025) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2025.07.007
Trastornos trombofílicos en la adolescente: el impacto ginecológico
Dietrich, J. E., & Yee, D. L. (2009) · Clínicas obstétricas y ginecológicas de Norteamérica
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
