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Association of Venous Thromboembolism With Hormonal Contraception and Thrombophilic Genotypes

Bergendal, Annica MD, PhD; Persson, Ingemar MD, PhD; Odeberg, Jacob MD, PhD; Sundström, Anders PhD; Holmström, Margareta MD, PhD; Schulman, Sam MD, PhD; Björgell, Ola MD, PhD; Kieler, Helle MD, PhD

doi: 10.1097/AOG.0000000000000411
Contents: Original Research

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.


Risk of venous thromboembolism associated with hormonal contraception differs by type and dose of the progestogen and by thrombophilic genotypes.

Department of Medicine, Karolinska Institutet, the Centre for Pharmacoepidemiology, Department of Medicine, Solna, Karolinska Institutet, the Coagulation Unit, Hematology Centre, and the Division of Clinical Pharmacology, Karolinska University Hospital, Stockholm, the Medical Products Agency, Uppsala, and the Department of Clinical Sciences/Medical Radiology, Diagnostic Centre of Imaging and Functional Medicine, Lund University, Lund, Sweden; and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Corresponding author: Annica Bergendal, MD, PhD, Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet SE-171 76 Stockholm, Sweden; e-mail:

Supported by unrestricted grants from Janssen-Cilag, Novartis, Organon, Schering, Wyeth, AFA Insurance, Center for Gender Medicine Karolinska Institutet, and the Medical Products Agency.

The authors thank Ebba Hallberg, Elisabet Stjernberg, and Annika Åkerström for data collection and study coordination; Anette Silvan for preparing DNA; and Kristina Holmberg for generating the genotyping data. Genotyping was performed at the KTH genotyping facility supported by the Wallenberg Consortium North.

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2014 by The American College of Obstetricians and Gynecologists.