Venous Thrombosis in Users of Non-Oral Hormonal Contraception: Follow-Up Study, Denmark 2001-10

Abstract

Conclusion: Women who use transdermal patches or vaginal rings for contraception have approximately a six to seven times increased risk of venous thromboembolism (VTE) compared to women who do not use hormonal contraception. Summary: It is well known oral contraceptive agents increase the risk of VTE. There are, however, little to no data regarding the effects of methods other than pills to deliver hormonal contraceptive agents. Such methods include transdermal patches, subcutaneous implants, and vaginal rings. The authors used a historic national registry in a cohort study design to assess absolute and relative risk of VTE in Danish women using nonoral hormonal contraception. This national registry-based cohort study used four national registries from Denmark. All Danish nonpregnant women aged 15 to 49 years (n = 1,626,158), who were free of previous VTE or cancer, were followed up from 2001 to 2010. The main outcome measures were incidence rates of VTE in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception. Relative risk of venous thrombosis was compared with nonusers of hormonal contraception, and rate ratios of venous thrombosis in current users of nonoral products were compared with the standard reference of an oral contraceptive with levonorgestrel and estrogen (30-40 μg). A diagnosis of VTE was considered confirmed if there was at least 4 weeks of anticoagulation therapy after the initial VTE diagnosis. There were 5,287 first ever VTE events recorded within 9,429,128 women-years of observation. Of these VTE events, 3,434 were confirmed. The rate of confirmed VTE events was 2.1/10,000 years in nonusers of hormonal contraception. After adjustment for age, calendar year, and education, the relative risks and 95% confidence interval (95% CI) of confirmed VTE in users of transdermal combined contraceptive patches and vaginal ring compared with nonusers of hormonal contraception were 7.9 (3.5-17.7) and 6.5 (7.4-8.9), respectively. Corresponding incidence events per 10,000 exposure-years were 9.7 and 7.8 events. The relative risk (95% CI) was increased in women who used subcutaneous implants (1.4 [0.6-3.4]) but not in those who use the levonorgestrel intrauterine system (0.6 [0.4-0.8]). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk (95% CI) of VTE was 2.3 (1.0-5.2) in users of transdermal patches and 1.9 (1.3-2.7) in users of the vaginal ring. Comment: In the last paragraph of the discussion portion of this article the authors succinctly point out the implications of their study, “if the incidence rate of venous thrombosis in women using combined oral contraceptives containing levonorgestrel is 6 per 10,000 exposure years, that of the vaginal ring is 11 per 10,000 exposure years, and that of the transdermal patch is 14 per 10,000 exposure years, then 2000 women using the vaginal ring, and 1250 using the transdermal patch should shift to combined oral contraceptives with levonorgestrel to prevent 1 event of VTE in one year. A risk of 10 per 10,000 years implies a risk of VTE more than 1% over a 10 year user period. Therefore, women are generally advised to use combined oral contraceptives with levonorgestrel or norgestimate, rather than to use transdermal patches or vaginal rings.”