Treatment with combined oral contraceptives induces a rise in serum C-reactive protein in the absence of a general inflammatory response
Open accessAbstract
Background The role of inflammation in the pathogenesis of cardiovascular disease is well established. C-reactive protein (CRP) is the strongest independent predictor of myocardial infarction and stroke in women. Recent studies have indicated that CRP levels are raised during use of combined oral contraceptives (COCs).Objectives The aim of the study was to investigate the effect of COCs on serum CRP levels and to indicate the underlying mechanisms of an expected increase.Method In a prospective randomized cross over-study 35 women used two different preparations of COC, one second and one third generation. Serum levels of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), antibodies against oxidized LDL, insulin and insulin-like growth factor-I (IGF-I) along with insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 were analyzed before and during the two treatments. E-selectin, von Willebrand factor and factor VIII concentrations in plasma were also measured.Results A rise in serum CRP was observed during both treatments; the median level increased from 0.45 mg L(-1) at baseline to 1.48 mg L(-1) with second generation and to 2.02 mg L(-1) with third generation COC. The serum levels of SAA increased slightly during treatment with the third generation COC. IL-6 and TNFalpha were unaffected by treatment. Both preparations lowered IGF-I and raised IGFBP-1 and IGFBP-3 concentrations.Conclusion The raised serum CRP concentration during treatment with COCs appears to be related to a direct effect on hepatocyte CRP synthesis and does not reflect IL-6 mediated inflammation, endothelial activation or induction of insulin resistance.
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Combined oral contraceptives increase low-grade inflammation, alter lipid metabolism and affect the coagulation system, resulting in an increased risk for thromboembolic events.
“COCs also increase low-grade inflammation, alter lipid metabolism and affect the coagulation system, resulting in an increased risk for thromboembolic events”
From Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial (2023) · cites this paper as van Rooijen et al., 2006
EE-containing COCs increase low-grade inflammation, reflected by increased levels of C-reactive protein (CRP).
“EE-containing COCs have been shown to increase low-grade inflammation, reflected by increased levels of C-reactive protein (CRP) (van Rooijen et al., 2006; Morin-Papunen et al., 2008; Haarala et al., 2009; Piltonen et al., 2012; Wang et al., 2016)”
From Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial (2023) · cites this paper as van Rooijen et al., 2006
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- Authors
- VAN ROOIJEN, M., HANSSON, L. O., FROSTEGÅRD, J., SILVEIRA, A., HAMSTEN, A., & BREMME, K.
- Affiliations
- Karolinska University Hospital (SE)
- Venue
- Journal of Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 4
- Issue
- 1
- Pages
- 77-82
- ISSN
- 1538-7836 (ISSN-L)
- OpenAlex
- W2009654724
- Cited by
- 105
- References
- 33
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 8 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 8
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- combined oral contraceptives, C-reactive protein, inflammation, cardiovascular risk in women, serum amyloid A, interleukin-6, TNF-α, insulin-like growth factor I, IGF binding proteins, oxidized LDL antibodies, endothelial activation, insulin resistance
- MeSH terms
- Adolescent, Adult, C-Reactive Protein, Contraceptives, Oral, Combined, Endothelium, Vascular, Female, Humans, Inflammation, Biomarkers, Cross-Over Studies, Hepatocytes, Glucose Metabolism Disorders
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