Hormonal Contraception Raises Thrombotic Stroke, MI Risk

View on the News

Not Risk-Free, But Safe Enough

"Women, their physicians, and the public should be reassured not only by the Danish study but by the vast body of evidence from epidemiologic studies of hormonal contraception that have been done over the past 5 decades," said Dr. Diana B. Petitti.

This study showed that the relative risks of thrombotic stroke and myocardial infarction "were increased by a factor of 1.5 to 2 among users of estrogen-progestin oral contraceptives with a low dose of ethinyl estradiol (30 to 40 mcg) for all the progestins studied (norethindrone, levonorgestrel, norgestimate, desogestrel, drospirenone, and cyproterone acetate). In a comparison of such low-dose formulations with different progestins, the relative risks of thrombotic stroke and myocardial infarction were statistically indistinguishable," she noted. Although the relative risk of thrombotic stroke was higher for users of the vaginal ring and the transdermal patch, the increases still were statistically indistinguishable.

"None of the hormonal contraceptives studied by Lidegaard and colleagues were associated with an excess risk of stroke that was unacceptable, considering their contraceptive and noncontraceptive benefits," Dr. Petitti said. "For an individual woman, the probability of an event is quite small."

Hormonal contraception is not risk free, but "the evidence is convincing" that it is "safe enough," she said.

Dr. Petitti is in the department of biomedical informatics at Arizona State University, Tucson. She reported no financial conflicts of interest. These remarks were taken from her editorial accompanying Dr. Lidegaard’s report (N. Engl. J. Med. 2012;366:2316-7).



Oral contraceptives containing low- or very low-dose estradiol raised the risks of thrombotic stroke and myocardial infarction by a factor of 1 to 2 in a large Danish cohort study. The results were published in the June 14 issue of the New England Journal of Medicine.

Although these risks were high relative to the nonuse of OCs, the absolute risks of thrombotic stroke and MI remained extremely low, said Dr. Øjvind Lidegaard and his associates at the University of Copenhagen.

"We estimate that among 10,000 women who use desogestrel with ethinyl estradiol at a dose of 20 mg for 1 year, 2 will have arterial thrombosis and 6.8 women ... will have venous thrombosis. Although venous thrombosis is three to four times as frequent as arterial thrombosis among young women, the latter is associated with higher mortality and more serious consequences for survivors. Therefore, these figures should be taken into account when prescribing hormonal contraception," they noted.

Few studies have examined the risks of thrombotic stroke and MI associated with the newer hormonal contraceptives, and those that have examined the issue have produced conflicting results. Dr. Lidegaard and his colleagues assessed this association in a cohort of Danish women aged 15-49 years in 1995 who were followed through 2009.

Among these 1,626,158 study subjects, there were 3,311 first thrombotic strokes and 1,725 first MIs during the 15-year follow-up. The case fatality rates were 1.0% for stroke and 10.8% for MI.

Compared with women who didn’t use hormonal contraceptives, those who used low-dose OCs (30-40 mcg estradiol) had a risk of arterial thrombosis that was 1.3-2.3 times higher, and women who used very-low-dose OCs (20 mcg estradiol) had a risk that was 0.9-1.7 times higher, the investigators said (N. Engl. J. Med. 2012;366:2257-66).

These risks did not vary significantly according to the different types of progestin contained in the OCs.

To put these risk elevations in context, it is useful to note that increasing age raised the risk of arterial thrombosis much more dramatically. The risk of thrombotic stroke was 20 times higher and that of MI was 100 times higher among the oldest study subjects – aged 45-49 years at baseline –compared with the youngest (15-19 years). Several previous studies also have noted the steep rise in thrombotic risk with increasing patient age, the researchers said.

Other hormonal contraceptive products also were assessed in this study. None of the contraceptive products that contained progestin only – such as the levonorgestrel-releasing IUD and subcutaneous implants – raised the risk of thrombotic stroke or MI significantly.

In contrast, contraceptive patches raised the relative risk of thrombotic stroke to 3.15, and vaginal rings raised it to 2.49. "One might expect a higher risk of thrombotic stroke with parenteral administration than with oral administration," Dr. Lidegaard and his associates said.

The number of MIs in these two subgroups of women was too low to allow for reliable estimates of MI risk.

This study was supported by the Danish Heart Association. Dr. Lidegaard reported ties to Bayer Pharma, MSD Denmark, and Theramex. Coinvestigator Ellen Løkkegaard, Ph.D., reported ties to Pfizer.

Recommended Reading

Sleeping Too Much or Too Little Puts Heart at Risk
MDedge Cardiology
Telestroke Triage Comes of Age
MDedge Cardiology
Elderly Stroke Patients Have High Atrial Fibrillation Prevalence
MDedge Cardiology
FDA Panel Questions Intracranial Stent Approval
MDedge Cardiology
Brain Aneurysm Guidelines Emphasize High-Volume Centers
MDedge Cardiology
Women's Stroke Risk Higher in AF, Regardless of Warfarin Use
MDedge Cardiology
Daily Aspirin Reduced Recurrent Venous Thromboembolism
MDedge Cardiology
Make the Most of 2013 Stroke Metrics Requirements
MDedge Cardiology
No Need to Bridge in Low-Risk Valve Patients
MDedge Cardiology
Predicted Survival Improves Patient Selection for CEA
MDedge Cardiology