Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes
Abstract
OBJECTIVE: To investigate associations between combined hormonal contraception and progestogen-only contraception and risks of venous thromboembolism by progestogen and carriership of genetic hemostatic variations. METHODS: This was a case-control study in Sweden carried out between 2003 and 2009, which included 948 patients with venous thromboembolism and 902 individuals in a control group, all aged 18-54 years. Information was obtained by telephone interviews and DNA analyses of blood samples. Radiologic referrals were used for case ascertainment. For comparisons, odds ratios were estimated by unconditional logistic regression analysis adjusting for smoking, body mass index (BMI), and immobilization. RESULTS: The odds ratio (OR) for current use of combined hormonal contraception was 5.3 (95% confidence interval [CI] 4.0-7.0). Desogestrel combinations had the highest OR (11.4, 95% CI 6.0-22.0). The OR for injection of medroxyprogesterone acetate was 2.2 (95% CI 1.3-4.0). In users of combined hormonal contraception with the factor V Leiden mutation, the OR was 20.6 (95% CI 8.9-58). In women who used progestogen-only contraception and carried the factor V Leiden mutation, the OR was 5.4 (95% CI 2.5-13). CONCLUSION: Risks of venous thromboembolism in association with combined hormonal contraception vary by type of progestogen and independently of BMI and smoking. Thrombophilic genotypes such as factor V Leiden increase risks of venous thromboembolism in users of combined hormonal contraception. Except for injection of medroxyprogesterone acetate, progestin-only contraception seems to be the least thrombogenic hormonal contraception for women carrying genetic hemostatic variations. LEVEL OF EVIDENCE: II.
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CHC has been shown to increase the risk of thrombosis.
“In patients with high risk of thrombosis who are not fully anticoagulated, CHC and injectable depot medroxyprogesterone acetate (DMPA) should be avoided, and is generally contraindicated, as both have been shown to increase the risk of thrombosis[104, 105].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [104]
Injectable progesterone such as DMPA may have a small increase in VTE risk.
“Progestin-only pills are generally considered safe, however, injectable progesterone such as DMPA may have a small increase in VTE risk [104, 105].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [104]
Injectable depot medroxyprogesterone acetate (DMPA) has been shown to increase the risk of thrombosis.
“In patients with high risk of thrombosis who are not fully anticoagulated, CHC and injectable depot medroxyprogesterone acetate (DMPA) should be avoided, and is generally contraindicated, as both have been shown to increase the risk of thrombosis[104, 105].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [104]
Progestin-only pills are generally considered safe in women with hereditary thrombophilia.
“Progestin-only pills are generally considered safe, however, injectable progesterone such as DMPA may have a small increase in VTE risk [104, 105].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [104]
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- Authors
- Bergendal, A., Persson, I., Odeberg, J., Sundström, A., Holmström, M., Schulman, S., Björgell, O., & Kieler, H.
- Affiliations
- Medical Products Agency (SE)
- Venue
- Obstetrics & Gynecology
- Published
- 2014-09
- Volume
- 124
- Issue
- 3
- Pages
- 600-609
- ISSN
- 0029-7844 (ISSN-L)
- OpenAlex
- W2052123395
- Cited by
- 93
- References
- 31
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 2
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Keywords
- venous thromboembolism, hormonal contraception, combined hormonal contraceptives, progestin-only contraception, desogestrel, medroxyprogesterone acetate, factor V Leiden, thrombophilia, thrombogenic risk
- MeSH terms
- Adult, Contraception, Contraceptives, Oral, Combined, Contraceptives, Oral, Hormonal, Factor V, Female, Humans, Middle Aged, Progestins, Risk Factors, Smoking, Sweden, Body Mass Index, Desogestrel, Point Mutation, Risk Assessment, Thrombophilia, Venous Thromboembolism
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