Risks for thrombotic stroke, MI slightly increased with use of hormonal contraception

Issue: July 2012

The risk for arterial thrombosis is 1.3 to 2.3 times higher among women who used oral contraceptives with ethinyl estradiol at a dose of 30 mcg to 40 mcg than women who did not use oral contraceptives, according to results of a 15-year Danish historical cohort study.

Additionally, women who used oral contraceptives with ethinyl estradiol at a dose of 20 mcg had a 0.9 to 1.7 times greater risk for arterial thrombosis compared with nonusers. There were only small differences according to progestin type, according to the New England Journal of Medicine study.

For the study, researchers followed nonpregnant women aged 15 to 49 years who had no history of CVD or cancer. Using four national registries, they obtained data on hormonal contraceptive use, clinical endpoints and potential confounders.

Examining long-term risk

In all, the researchers studied 1,626,158 women who contributed more than 14.2 million person-years of observation. During the 15-year study period, 1,725 MIs (10.1 per 100,000 person-years) and 3,311 thrombotic strokes (21.4 per 100,000 person-years) occurred.

Compared with nonusers, women who used oral contraceptives containing ethinyl estradiol at a dose of 30 mcg to 40 mcg had the following risks for thrombotic stroke and MI, according to progestin type:

norethindrone: RR for stroke=2.2 (95% CI, 1.5-3.2) and RR for MI=2.3 (95% CI, 1.3-3.9)
levonorgestrel: RR for stroke=1.7 (95% CI, 1.3-2) and RR for MI=2 (95% CI, 1.6-2.5)
norgestimate: RR for stroke=1.5 (95% CI, 1.2-1.9) and RR for MI=1.3 (95% CI, 0.9-1.9)
desogestrel: RR for stroke=2.2 (95% CI, 1.8-2.7) and RR for MI=2.1 (95% CI, 1.5-2.8)
gestodene: RR for stroke=1.8 (95% CI, 1.6-2) and RR for MI=1.9 (95% CI, 1.6-2.3)
drospirenone: RR for stroke=1.6 (95% CI, 1.2-2.2) and RR for MI=1.7 (95% CI, 1-2.6).

When the researchers examined oral contraceptives containing ethinyl estradiol at a dose of 20 mcg, the corresponding RRs according to progestin type were:

desogestrel: RR for stroke=1.5 (95% CI, 1.3-1.9) and RR for MI=1.6 (95% CI, 1.1-2.1)
gestogene: RR for stroke=1.7 (95% CI, 1.4-2.1) and RR for MI=1.2 (95% CI, 0.8-1.9)
drospirenone: RR for stroke=0.9 (95% CI, 0.2-3.5) and RR for MI=0

“We estimate that among 10,000 women who use desogestrel with ethinyl estradiol at a dose of 20 mcg for 1 year, two will have arterial thrombosis and 6.8 women taking the same product will have venous thrombosis,” the researchers wrote in the study. “These figures should be taken into account when prescribing hormonal contraception.”

Women who used transdermal patches had a corresponding RR of 3.2 (95% CI, 0.8-12.6) for stroke and a RR of 0 for MI. Vaginal ring users had a corresponding RR of 2.5 (95% CI, 1.4-4.4) for stroke and 2.1 (95% CI, 0.7-6.5) for MI.

Reasons behind the increase

According to the researchers, the increased incidence of thrombotic stroke during the study is probably related to “improvements in diagnostic equipment, allowing the detection of small cerebral infarctions, rather than a real increase in incidence.”

For more information:

Lidegaard O. N Engl J Med. 2012;366:2257-2266.

Disclosure: Dr. Lidegaard reports receiving grant support from Bayer Pharma; lecture fees and travel reimbursements from Bayer Denmark, MSD Denmark and Theramex, and providing testimony in a US legal case on oral contraception and venous thromboembolism. Dr. Løkkegaard reports receiving travel reimbursements from Pfizer.