Hormonal contraception and risk of venous thromboembolism: national follow-up study

Lidegaard, O.; Lokkegaard, E.; Svendsen, A. L.; Agger, C.

doi:10.1136/bmj.b2890

Cited by 712Venous Thromboembolism Diagnosis and ManagementReproductive Health and ContraceptionBlood Coagulation and Thrombosis Mechanisms

Hormonal contraception and risk of venous thromboembolism: national follow-up study

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Lidegaard, O., Lokkegaard, E., Svendsen, A. L., Agger, C.·2009·BMJ

DOI 10.1136/bmj.b2890PMC PMC2726928

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Abstract

OBJECTIVE: To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. DESIGN: National cohort study. SETTING: Denmark, 1995-2005. PARTICIPANTS: Danish women aged 15-49 with no history of cardiovascular or malignant disease. MAIN OUTCOME MEASURES: Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. RESULTS: 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 mug desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26). CONCLUSION: The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.

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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 Lidegaard et al., 2009
COCs increase the risk of thromboembolic events.
“It is also well known that COCs increase the risk of thromboembolic events (Sitruk-Ware et al., 2007a; Lidegaard et al., 2009, 2012; de Bastos et al., 2014).”
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 Lidegaard et al., 2009

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Authors: Lidegaard, O., Lokkegaard, E., Svendsen, A. L., & Agger, C.
Affiliations: University of Copenhagen (DK)
Venue: BMJ
Publisher: BMJ
Published: 2009-08-13
Volume: 339
Issue: aug13 2
Pages: b2890-b2890
ISSN: 0007-1447 (ISSN-L)
0959-8138
1468-5833
DOI: 10.1136/bmj.b2890
PMC: PMC2726928
OpenAlex: W2027062965
Cited by: 709
References: 29
Citations by year: 2026: 19 · 2025: 39 · 2024: 17 · 2023: 27 · 2022: 35 · 2021: 42 · 2020: 33 · 2019: 31 · 2018: 34 · 2017: 46 · 2016: 32 · 2015: 41 · 2014: 61 · 2013: 74 · 2012: 45
FWCI: 44.51
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: BMJ (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: Rigshospitalet
Topics: Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords: hormonal contraception, venous thromboembolism, deep vein thrombosis, pulmonary embolism, oral contraceptives, estrogen dose, progestogens, levonorgestrel, norethisterone, desogestrel, gestodene, drospirenone, cyproterone, route of administration, duration of use, thrombosis risk
MeSH terms: Adolescent, Adult, Contraceptives, Oral, Combined, Contraceptives, Oral, Hormonal, Denmark, Epidemiologic Methods, Female, Humans, Middle Aged, Age Distribution, Venous Thromboembolism, Young Adult

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Hormonal contraception and risk of venous thromboembolism: national follow-up study

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