NEW YORK (Reuters Health) – The largest study to ever assess the risks of hormone-based birth control has concluded that the contraceptives are linked with a small elevated risk of stroke and heart attack, depending on the type of hormone used.
The risk for individual women remains extremely low, particularly in younger women, and progestin-based contraceptives pose a much smaller risk.
However, the study in the June 14 New England Journal of Medicine raises questions about whether methods such as transdermal patches or vaginal rings may be linked with an unexpectedly elevated risk of stroke.
“Our data suggest a relatively high risk of thrombotic stroke with the use of a vaginal ring and possibly with the use of transdermal patches,” said the team, led by Dr. Ojvind Lidegaard of Copenhagen University Hospital.
But Dr. James Simon of George Washington University, who was not involved in the research, told Reuters Health in a telephone interview that other factors, such as the belief that a patch or a ring might be safer for women thought to be a high risk, may explain the higher rate of stroke in that group.
He said the overall findings of the study probably shouldn’t change prescribing practices. The risks seen in the new research pale in comparison to the risks of stroke, heart attack or death conferred by pregnancy.
“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. Diana Petitti of Arizona State University in Phoenix said in a Journal editorial.
Previous attempts to assess the risk of thrombotic stroke or myocardial infarction have been conflicting.
The Lidegaard team analyzed data on 1.63 million Danish women ages 15 to 49, to assess the potential dangers. The women, all without a history of cardiovascular disease or cancer, were followed for 15 years beginning in 1995.
The per-person risk in contraceptive users was small: 0.0214% per year for stroke and 0.0101% per year for heart attack.
By contrast, in non-users, the per-person risks were 0.0242% per year for stroke and 0.0132% per year for heart attack, “with the higher rates primarily due to older age and a higher frequency of predisposing conditions among non-users,” the researchers said.
Compared with non-use, the relative risks for thrombotic stroke and heart attack for combination pills that included 30 to 40 mcg of ethinyl estradiol ranged from 1.5 and 1.3, respectively, with norgestimate, to 2.2 and 2.3 with norethindrone,
But Dr. Simon said the new research “shows very little difference between the different pills for the same dose of estrogen, which will make women’s choices larger. Right now you have the perception that certain pills have more or less risk. This should dissuade them from that and open up to practitioners greater choices for their patients.”
On the other hand, “None of the progestin-only products, including the levonorgestrel-releasing IUD and the subcutaneous implants, significantly increased the risk of thrombotic stroke or myocardial infarction, but the numbers were small for several of these groups,” the researchers said. “In contrast, the relative risk of thrombotic stroke was 3.15 (95% CI, 0.79 to 12.6) among women who used contraceptive patches and 2.49 (95% CI, 1.41 to 4.41) among those who used a vaginal ring. Numbers of myocardial infarctions were too low to provide reliable estimates.”
Dr. Lidegaard told Reuters Health in a telephone interview that many women have used patches and rings “believing that these non-oral products could confer less risk. But this is definitely not the case.”
But they have other long-term alternatives that use progestin. “Women can take progestin products such as IUD, progesterone-only pills or subcutaneous implants. All three products don’t increase the risk of thrombotic events at all.”
Dr. Lidegaard said age is a key consideration.
“If you are 20 years old and you double your risk of arterial complications, then you still have a very low risk because the absolute risk is so low,” he said. “On the other hand, if you are in the other path of reproductive age, especially in the 40s, you should consider not increasing your risk of thrombolytic complications further because it’s already increased due to your age.”
The researchers also found that women with the highest education levels “had about half as many thrombotic strokes and about one third as many myocardial infarctions as women with the lowest level of education.”
And among all women, once they stopped using hormonal contraception, the risk dropped to the same level as it did for women who had never used them. Compared to nonusers, the risk of thrombotic stroke among previous users was 1.04 (95% CI, 0.95 to 1.15) and the chance of heart attack was 0.99 (CI 0.86 to 1.13).
Dr. Simon said women who think the findings mean they should stop taking contraceptives are getting the wrong message because the risks associated with pregnancy are so much greater.
Dr. Petitti, in her Journal editorial, said, “The research shows that the small risk could be minimized and perhaps eliminated by abstinence from smoking and by checking blood pressure, with avoidance of hormonal contraceptive use if blood pressure is raised.”
N Engl J Med 2012; 366:2257-2266.