Venous thromboembolism risk: Not all oral contraceptives are created equal

December 1, 2011

Women taking oral contraceptives (OCs) containing desogestrel, gestodene, or drospirenone have at least twice the risk for venous thromboembolism (VTE) as those who take OCs containing levonorgestrel.

Women taking oral contraceptives (OCs) containing desogestrel, gestodene, or drospirenone have at least twice the risk for venous thromboembolism (VTE) as those who take OCs containing levonorgestrel.

Researchers from Denmark and Norway conducted a registry-based cohort study using four Danish registries. They included nonpregnant women between the ages of 15 and 49 years without a history of thrombotic disease and followed them for 8 years.

Compared with nonusers of hormonal contraception, those taking OCs containing 30 µg to 40 µg levonorgestrel were at almost 3 times the risk for VTE (relative risk [RR], 2.9; 95% confidence interval [CI], 2.2-3.8), and those taking OCs containing desogestrel, gestodene, or drospirenone were at more than 6 times the risk (RR, 6.6, 5.6-7.8; RR, 6.2, 5.6-7.0; and RR, 6.4, 5.4-7.5, respectively).

Progestogen-only pills and hormone-releasing uterine devices did not affect the risk. The relative risk for VTE from using OCs with norethisterone, levonorgestrel, desogestrel, or gestodene decreased with decreasing estrogen dose, whereas reducing the amount of estrogen from 30 µg to 20 µg in OCs containing drospirenone did not reduce the risk for VTE.

The authors estimate that approximately 2,000 women would need to switch from OCs containing desogestrel, gestodene, or drospirenone to those containing levonorgestrel to prevent one event of VTE in 1 year.

Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Lokkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ. 2011;343:d6423. doi: 10.1136/bmj.d6423.

Dr. Lockwood comments: This study provides further evidence that the relatively new, so-called third-generation 19-nortestosterone derivative progestins increase the risk of deep venous thrombosis compared with earlier, more androgenic progestins. In this latest study the risk begins to approach that seen in pregnancy, although prior epidemiological studies suggested a lower, albeit relatively increased, risk. In my opinion, these agents should be used in women who are at low a priori risk of thrombosis (ie, thin, active, nonsmoking women without affected first-degree relatives or a known thrombophilia, and who are under 35 years of age).