The composition of a woman’s contraceptive pill influences her risk of developing blood clots of the leg and lung, European researchers say.
Scientists have long known that oral contraceptives, which contain the female hormones estrogen and progestogen, increase the likelihood of deep vein thrombosis of the leg and pulmonary embolism, but new studies in Denmark and the Netherlands determined that some pills are safer than others. Neither study received funding from any companies that make oral contraceptives.
Pills containing a second-generation progestogen — levonorgestrel or norgestrel — and a low dose of estrogen are safest, they concluded.
The overall risk of venous thromboembolism is low, perhaps three for 10,000 woman-years for women in general, said Dr. Ojvind Lidegaard, a professor of obstetrics and gynecology at the Rigshospitalet in Copenhagen, and lead author of one of two reports in the Aug. 14 online issue of BMJ. But older contraceptive pills double or triple that risk, and the newest generation of oral contraceptives increase the risk fourfold or fivefold, he said.
A first message from the studies is that “the risk when you are taking an oral contraceptive depends on both the estrogen dose and the progestogen dose, and the lower the dose, the less risk,” Lidegaard said.
Both studies found that the risk decreases with the length of time a woman takes a combination pill, and that progestogen-only pills and the use of hormone-releasing intrauterine devices are not associated with an increased risk.
The Dutch study, which compared 1,524 women under the age of 50 who had deep venous thromboembolisms with 1,760 women with no such history, found a fivefold increased risk in oral contraceptive users. The risk of an event was highest in the first three months of use and lowest with pills containing levonorgestrel.
Pills with equal doses of estrogen that contained the progestogen desogestrel had double the risk of the pills using levonorgestrel, the researchers found.
The Danish study of all women aged 15 to 49 from 1995 to 2005 found roughly the same association.
In general, the newer oral contraceptives have a higher risk than the older ones, Lidegaard said. “The fourth-generation pills are not safer than the first-generation pills, which we had not expected,” he said.
For women who want to use an oral contraceptive and are at higher risk because of obesity or a family history of venous thromboembolism, “it would be wise to take a second-generation product,” Lidegaard said.
While the study looked at oral contraceptives marketed in Europe, the results apply to “all women in industrial countries,” said Dr. Astrid van Hylckama Vlieg, a research fellow in the department of clinical epidemiology at Leiden University and a member of the Dutch research team.
“In the United States, you have several products we describe,” she said.
It won’t be easy for a woman to act on the information in the studies, she said. “By just looking at the package, you can’t tell which generation of progestogen is used,” she said. A consultation with the physician writing the prescription is advisable, she said.
“The message of these studies is that all the pills are effective as contraceptives if taken as directed, and that side effects have to do with the choice of pill,” said Dr. Nick Dunn, a senior lecturer in medical education at the University of Southampton Medical School in England, who wrote an accompanying editorial.
While the risk of venous blood clots is very small, it cannot be disregarded, Dunn said. “Women with any sort of family history should think very carefully before taking any contraceptive pill,” he said. “These papers strongly suggest that there are safer pills among the choices that are available.”