medwireNews: Women who use combination estrogen–progestin and some forms of progestin-only contraceptives are at increased risk for ischemic stroke and myocardial infarction (MI) compared with nonusers, suggests a study published in The BMJ.
Investigators Harman Yonis (Nordsjaellands Hospital, Hilleroed, Denmark) and colleagues say that the increased arterial thrombotic risks with hormonal contraception “translated to low absolute excess risks,” given the low baseline risk among women of reproductive age.
Nevertheless, they caution that “clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method.”
The team analyzed data for all 2,025,691 women aged 15–49 years living in Denmark between 1996 and 2021 who had no history of arterial or venous thrombosis, gynecologic disorders, or other major illnesses. The women were followed-up for 22,209,697 person–years, during which time 4730 women developed ischemic stroke and 2027 MI, giving rates of 39 and 18 events per 100,000 person–years, respectively.
The study determined the rate of stroke and MI for women using combined contraception orally (ethinyl estradiol 30–40 µg, ethinyl estradiol 20 µg, or oral estradiol in combination with a progesterone, such as levonorgestrel, gestodene, or drespirenone), or via vaginal ring or patch, versus women with no hormonal contraceptive use. The rates were also determined for women using progestin-only contraception given orally or by intrauterine device (IUD), implant, or injection.
The nonuser comparator group were followed-up for 14,894,594 person–years, were aged a mean of 34 years, had a mean BMI of 23 kg/m2, and 18.8% had a history of smoking. No more than 1% had diabetes, hypercholesterolemia, or atrial fibrillation or flutter at baseline.
The average age of women using the different forms of hormone contraception ranged from 19–38 years, the mean BMI ranged from 22–24 kg/m2, the average proportion of women with a history of smoking ranged from 7.2–44.7%, and on average there were low rates of diabetes (0.6–3.3%), hypertension (0.1–0.6%), hypercholesterolemia (0–1.4%), and atrial fibrillation or flutter (0–0.4%).
The most commonly used hormonal contraceptive was oral ethinyl estradiol 30–40 µg plus levonorgestrel, with 1,608,798 person–years of follow-up, while the most common progestin-only contraceptive used was the IUD with 977,191 person–years of follow-up.
Among the nonusers, the standardized rate of ischemic stroke was 18 per 100,000 person–years versus 39 per 100,000 person–years for women using an oral combined contraceptive, 33 per 100,000 person–years for oral progestin-only users, and 23 per 100,000 person–years for women with a progestin-only IUD.
The corresponding standardized rates for MI were 8, 18, 13, and 11 per 100,000 person–years, the researchers report.
After adjusting for age, calendar time, education, diabetes, hypertension, hypercholesterolemia, atrial fibrillation or flutter, the adjusted incidence rate ratio (aRR) for use of combination oral contraceptives versus no use was a significant 2.0 for both ischemic stroke and MI, translating to 21 extra ischemic strokes and 10 extra MIs per 100,000 person–years with oral combination contraceptive use.
The aRRs for ischemic stroke and MI with progestin-only oral use were a significant 1.6 and 1.5, respectively, versus no use, resulting in 15 and four extra events, respectively, per 100,000 person–years.
And the researchers also point to a significantly increased risk for ischemic stroke with use of a combination vaginal ring (aRR=2.4), combination hormone patch (aRR=3.4), or progestin-only implant (aRR=2.1) versus no use. The combination vaginal ring was also associated with a significantly increased risk for MI versus no hormone contraceptive use (aRR=3.8).
By contrast, use of a progestin-only IUD was not associated with an increased risk for ischemic stroke or MI, say Yonis et al.
In a linked editorial, Therese Johansson (Royal Institute of Technology, Stockholm, Sweden) agrees with the authors that the risk for arterial thrombosis events overall is low but notes that “these side effects are serious and given that approximately 248 million women use hormonal contraceptives daily, the results carry important implications.”
Johansson highlights that the levonorgestrel-releasing IUD was the only hormonal contraceptive not linked to an increased risk, therefore “making this option safer for cardiovascular health.”
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