Levonorgestrel, low-dose estrogen associated with lower risk for adverse vascular events among oral contraceptives

Compared with other estrogen doses and progestogen types, low-dose estrogen with levonorgestrel had a decreased risk of adverse events.
Compared with other estrogen doses and progestogen types, low-dose estrogen with levonorgestrel had a decreased risk of adverse events.

Oral contraceptives that combine levonorgestrel and 20 μg of estrogen are associated with lower risks of pulmonary embolism, stroke, and myocardial infarction, compared with other combinations of progestogen types and estrogen doses, according to a study published in BMJ.

“For the same dose of [estrogen], desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel,” wrote the researchers. “For the same type of progestogen, an [estrogen] dose of 20 µg versus 30 to 40 µg was associated with lower risks of pulmonary embolism, ischaemic stroke, and myocardial infarction.”

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The study, led by Alain Weill, MD, from the Department of Studies in Public Health of the French National Health Insurance, used data from the French national health insurance database and the French national hospital discharge database, including 4,945,088 women aged 15 to 49 years who had at least 1 reimbursement for oral contraceptives between July 2010 and September 2012. The researchers excluded women with a history of cancer, pulmonary embolism, ischemic stroke, or myocardial infarction.

During the study period, 8 combinations of estrogen and progestogen were used under 26 brand names. They differed by estrogen dose (20 μg to 50 μg) and progestogen type (norethisterone, levonorgestrel, desogestrel, gestodene, or norgestrel).

In the follow-up period, 3,252 primary outcome events were recorded: 1,800 pulmonary embolisms (33 per 100,000 women-years), 1,046 ischemic strokes (19 per 100,000 women-years), and 407 myocardial infarctions (7 per 100,000 women-years).

After adjusting for progestogen type and risk factors, women using low-dose estrogen (20 μg) had relative risks of 0.75 for pulmonary embolism, 0.82 for ischemic stroke, and 0.56 for myocardial infarction compared with women using 30 to 40 μg of estrogen.

After adjusting for estrogen dose and risk factors, the authors found that women using contraceptives containing desogestrel or gestodene had significantly higher relatives risks for pulmonary embolism (2.16 and 1.63, respectively) compared with those using contraceptives containing levonorgestrel.

The combination of levonorgestrel and 20 μg of estrogen had significantly lower risks of pulmonary embolism, ischemic stroke, and myocardial infarction compared with levonorgestrel and 30 to 40 μg of estrogen.

Reference

  1. Weill A, Dalichampt M, Raguideau F, et al. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study. BMJ. 2016; 353.
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