October 26th, 2011

Danish Study Clarifies VTE Risk Associated with Newer Progestogens in Oral Contraceptives

A large new study from Denmark provides the best evidence yet that third-generation oral contraceptives (OCs) containing drospirenone, desogestrel, or gestodene (sometimes used to treat dysmenorrhea) are associated with twice the risk for venous thromboembolism (VTE) as second-generation OCs containing levonorgestrel.

In a paper published in BMJ,  Øjvind Lidegaard and colleagues analyzed data from national registries containing more than 8 million woman-years of observation, including 2847 confirmed VTE events.

Here are the relative risks for VTE with OCs when compared to no hormonal contraception (all OCs also contained 30-40 μg ethinyl estradiol):

  • levonorgestrel: 2.9 (CI 2.2 – 3.8)
  • desogestrel: 6.6 (5.6 – 7.8)
  • gestodene: 6.2 (5.6 – 7.0)
  • drospirenone: 6.4 (5.4 – 7.5)

Here are the relative risks with the newer OCs compared to those containing levonorgestrel, after adjustment for length of use:

  • desogestrel: 2.2 (1.7 – 3.0)
  • gestodene: 2.1 (1.6 – 2.8)
  • drospirenone: 2.1 (1.6 – 2.8)

The authors calculated that to prevent one VTE event in 1 year, 2000 women would need to switch from an OC containing a newer progestogen to an OC containing levonorgestrel.

In an accompanying editorial, Philip Hannaford writes:

Although unpalatable to some, it is difficult not to conclude that combined oral contraceptives with desogestrel, gestodene, or drospirenone confer a higher risk of venous thromboembolism than those with levonorgestrel. Many clinicians will choose to minimise the risk by prescribing a combined oral contraceptive with levonorgestrel whenever possible. It is crucial, however, not to exaggerate the risk—oral contraceptives are remarkably safe and may confer important long term benefits in relation to cancer and mortality.


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