Thrombotic stroke and myocardial infarction with hormonal contraception
Abstract
BACKGROUND: Although several studies have assessed the risk of venous thromboembolism with newer hormonal contraception, few have examined thrombotic stroke and myocardial infarction, and results have been conflicting. METHODS: In this 15-year Danish historical cohort study, we followed nonpregnant women, 15 to 49 years old, with no history of cardiovascular disease or cancer. Data on use of hormonal contraception, clinical end points, and potential confounders were obtained from four national registries. RESULTS: A total of 1,626,158 women contributed 14,251,063 person-years of observation, during which 3311 thrombotic strokes (21.4 per 100,000 person-years) and 1725 myocardial infarctions (10.1 per 100,000 person-years) occurred. As compared with nonuse, current use of oral contraceptives that included ethinyl estradiol at a dose of 30 to 40 μg was associated with the following relative risks (and 95% confidence intervals) for thrombotic stroke and myocardial infarction, according to progestin type: norethindrone, 2.2 (1.5 to 3.2) and 2.3 (1.3 to 3.9); levonorgestrel, 1.7 (1.4 to 2.0) and 2.0 (1.6 to 2.5); norgestimate, 1.5 (1.2 to 1.9) and 1.3 (0.9 to 1.9); desogestrel, 2.2 (1.8 to 2.7) and 2.1 (1.5 to 2.8); gestodene, 1.8 (1.6 to 2.0) and 1.9 (1.6 to 2.3); and drospirenone, 1.6 (1.2 to 2.2) and 1.7 (1.0 to 2.6), respectively. With ethinyl estradiol at a dose of 20 μg, the corresponding relative risks according to progestin type were as follows: desogestrel, 1.5 (1.3 to 1.9) and 1.6 (1.1 to 2.1); gestodene, 1.7 (1.4 to 2.1) and 1.2 (0.8 to 1.9); and drospirenone, 0.9 (0.2 to 3.5) and 0.0. For transdermal patches, the corresponding relative risks were 3.2 (0.8 to 12.6) and 0.0, and for a vaginal ring, 2.5 (1.4 to 4.4) and 2.1 (0.7 to 6.5). CONCLUSIONS: Although the absolute risks of thrombotic stroke and myocardial infarction associated with the use of hormonal contraception were low, the risk was increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 μg and by a factor of 1.3 to 2.3 with those that included ethinyl estradiol at a dose of 30 to 40 μg, with relatively small differences in risk according to progestin type. (Funded by the Danish Heart Association.).
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Estrogen is associated with increased risk of arterial thrombosis.
“Estrogen has also been associated with increased risk of “unusual site” thromboses, as well as arterial thrombosis.”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [98]
A study of more than a million women aged 15 to 49 by Lidegard et al showed an increased risk of stroke and myocardial infarction associated with use of CHC, estimated at a factor of 0.9 to 2.3 based on the estrogen dose and component.
“In 2012, a study of more than a million women aged 15 to 49 by Lidegard et al showed an increased risk of stroke and myocardial infarction (MI) associated with use of CHC, estimated at a factor of 0.9 to 2.3 based on the estrogen dose and component.”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [98]
Progestin-only methods such as oral pills, levonorgestrel IUD, and the progestin subdermal implant have not been shown to increase risk of VTE.
“Options include the copper IUD and progestin-only methods such as oral pills, levonorgestrel IUD, and the progestin subdermal implant, may induce amenorrhea, and have not been shown increase risk of VTE (contrary to etonogestrel implant package labeling) [98].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [98]
The absolute risk of cardiovascular disease associated with the use of combined oral contraceptives is low (about 10 per 100 000 person years for myocardial infarction and 21 per 100 000 person years for stroke).
“the absolute risk of cardiovascular disease associated with the use of combined oral contraceptives is low (about 10 per 100 000 person years for myocardial infarction and 21 per 100 000 person years for stroke)”
From Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review (2020) · cites this paper as [21]
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- Authors
- Lidegaard, Ø., Løkkegaard, E., Jensen, A., Skovlund, C. W., & Keiding, N.
- Affiliations
- University of Copenhagen (DK)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-06-14
- Volume
- 366
- Issue
- 24
- Pages
- 2257-2266
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2146576387
- Cited by
- 607
- References
- 30
- Citations by year
- 2026: 29 · 2025: 28 · 2024: 43 · 2023: 38 · 2022: 31 · 2021: 43 · 2020: 34 · 2019: 40 · 2018: 39 · 2017: 45 · 2016: 57 · 2015: 51 · 2014: 50 · 2013: 59 · 2012: 18
- FWCI
- 54.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- thrombotic stroke, myocardial infarction, hormonal contraception, oral contraceptives, progestins, norethisterone, levonorgestrel, desogestrel, drospirenone, cardiovascular risk, women of reproductive age, venous thromboembolism, relative risk, confounding
- MeSH terms
- Administration, Cutaneous, Adolescent, Adult, Contraceptive Agents, Contraceptives, Oral, Combined, Educational Status, Estradiol, Female, Humans, Middle Aged, Myocardial Infarction, Progestins, Regression Analysis, Risk, Smoking, Thrombosis, Cohort Studies, Incidence, Stroke, Intracranial Thrombosis, Young Adult
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