Third-Generation Oral Contraceptives Associated with Greater Risk of PE, Stroke, and MI


Am Fam Physician. 2016 Oct 15;94(8):663.

Clinical Question

Which oral contraceptive combinations have the highest risk of cardiovascular effects?

Bottom Line

Although there is risk with any current oral contraceptive combination, those that contain lower doses of estrogen, and levonorgestrel instead of desogestrel or gestodene, are associated with the least risk of ischemic stroke, myocardial infarction (MI), or pulmonary embolism (PE). These safer products are older so are often less expensive. This is not the first study to show this difference, but its enrollment of 5 million women may make it the largest. (Level of Evidence = 2b)


This study, conducted in France, used the national health insurance database to identify all women who filled at least one prescription for an oral contraceptive between July 2010 and September 2012. The authors compared these data with the hospital discharge database to identify whether any of these women experienced an admission for PE, cancer, ischemic stroke, or MI over the same period. They identified almost 5 million women with a total of 5,443,916 woman-years of oral contraceptive use.

The risk of cardiovascular effects was very low: roughly six events per 10,000 woman-years, which is similar to other reports. However, the authors found some differences among products: After adjustment for progestogen and risk factors, stroke, PE, and MI risk were all statistically lower with lower-dose estrogen (20 mcg vs. 30 to 40 mcg). They also found, after adjustment, that progestogen mattered: desogestrel (in Desogen, Mircette) and gestodene (Gynera, Femoden, and many others) were associated with higher risk of PE than levonorgestrel. Norethisterone (in Loestrin, Microgestin, and others) was associated with lower PE risk. The combination of estrogen, 20 mcg, and levonorgestrel is associated with the lowest risk. These risks are still small (numbers needed to treat to harm are in the thousands). This study does not tell us about products that contain other estrogens or progestogens because these are the only combinations covered by French national health insurance. Also, the database does not allow for analysis by smoking status.

Study design: Cohort (retrospective)

Funding source: Foundation

Setting: Population-based

Reference: 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:i2002.

POEMs (patient-oriented evidence that matters) are provided by EssentialEvidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, Associate Deputy Editor.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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