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Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study
10 May 2016
Cite this as: [BMJ 2016;353:i2002]
Alain Weill, epidemiologist1, Marie Dalichampt, statistician1, Fanny Raguideau, epidemiologist2, Philippe Ricordeau, head1, Pierre-Olivier Blotière, statistician1, Jérémie Rudant, epidemiologist1, François Alla, professor of public health1, Mahmoud Zureik, scientific director2

Le bon choix : EE 20 µg + Lévonorgestrel.
Pour les mêmes doses d'oestrogène, comparé au lévonorgestrel le désogestrel and gestodène sont associés à une augmentation statistiquement significative du risque d'embolie pulmonaire. Pour le même type de progestatif, 20µg d'EE versus 30 ou 40µg est associé aà une diminution du risque d'embolie pulmonaire, d'AVC ischémique et d'infarctus du myocarde (Exemple :Leeloo, Lovavulo, etc...)
What this study adds
-For the same progestogen, using an oestrogen dose of 20 µg compared with 30-40 µg was associated with lower risks of pulmonary embolism, ischaemic stroke, and myocardial infarction
-Oral contraceptives containing levonorgestrel with 20 µg of oestrogen was the combination associated with the overall lowest risk of pulmonary embolism and arterial thromboembolism

Objective To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen.

Design Observational cohort study.

Setting Data from the French national health insurance database linked with data from the French national hospital discharge database.

Participants 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012.

Main outcome measures Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction.

Results The cohort generated 5?443?916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100?000 women years), 1046 ischaemic strokes (19 per 100?000 women years), and 407 myocardial infarctions (7 per 100?000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events.

Conclusions For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel. For the same type of progestogen, an oestrogen dose of 20 µg versus 30-40 µg was associated with lower risks of pulmonary embolism, ischaemic stroke, and myocardial infarction.

[Texte complet / BMJ 2016]
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