Lidegaard, O., Nielsen, L. H., Skovlund, C. W., & Løkkegaard, E. (2012). Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ (Clinical Research Ed.), 344(may10 3), e2990. https://doi.org/10.1136/bmj.e2990
Lidegaard O, Nielsen LH, Skovlund CW, Løkkegaard E. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ. 2012;344(may10 3):e2990. doi:10.1136/bmj.e2990
Lidegaard, Ojvind, et al. "Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10." BMJ (Clinical Research Ed.), vol. 344, no. may10 3, 2012, pp. e2990.
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Contraceptive Patches and Vaginal Rings Carry the Highest Clot Risk
Patch and ring users had the highest blood clot risk of any method studied, in a national registry study of 1,626,158 Danish women aged 15 to 49, followed from 2001 to 2010. The levonorgestrel IUS showed a lower risk than non-users.
Study at a glance, cohort study of 1,626,158 Danish women: Patch and vaginal ring users had the highest clot risk. Source: Lidegaard O et al., 2012, PMID 22577198.
Key Findings
Transdermal patch users had an adjusted relative risk of confirmed venous thrombosis of 7.9 (95% CI 3.5 to 17.7) versus non-users, or 9.7 events per 10,000 exposure-years.
Vaginal ring users had an adjusted relative risk of 6.5 (4.7 to 8.9) versus non-users, or 7.8 events per 10,000 exposure-years.
Compared with oral contraceptives containing levonorgestrel, the patch carried 2.3 times the risk (1.0 to 5.2) and the ring 1.9 times the risk (1.3 to 2.7).
Subcutaneous implant users had a modest increase in risk versus non-users that did not reach statistical significance (relative risk 1.4, 0.6 to 3.4).
Levonorgestrel intrauterine system users had a significantly lower risk than non-users (relative risk 0.6, 0.4 to 0.8).
Interpretation
This cohort study followed 1,626,158 Danish women aged 15 to 49 from 2001 to 2010. The researchers drew on four linked national registries and 9,429,128 woman-years of follow-up. Exposure data came straight from the national prescription database. The authors call this the most reliable exposure data available, and say it removes recall bias. They also say the decade-long national coverage gives the study strong external validity. The authors note they could not adjust for body mass index or family clotting history, both known risk factors for clots. The findings support larger studies of clot risk across hormonal contraceptive delivery methods.
RRM Context
This fits a broader pattern in research: how a hormone is delivered can matter as much as which hormone it is. Patches, rings, pills, and implants each deliver hormones in a different way. Fertility awareness-based methods used to avoid pregnancy add no hormones at all, so they carry none of this clot risk.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To assess the risk of venous thrombosis in current users of non-oral hormonal contraception.
Design
Historical national registry based cohort study.
Setting
Four national registries in Denmark.
Participants
All Danish non-pregnant women aged 15-49 (n=1,626,158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010.
Main Outcome Measures
Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis.
Results
Within 9,429,128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10,000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10,000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7).
Conclusion
Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10,000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.
