Which Birth Control Pill Is Safest?

Researchers Find Differences in Blood Clot Risk in Different Oral Contraceptives

Medically Reviewed by Louise Chang, MD on August 13, 2009
From the WebMD Archives

Aug. 13, 2009 -- When it comes to the risk of blood clots, some oral contraceptive pills are safer than others, according to new studies by European researchers.

"Oral contraceptives with levonorgestrel and a low dose of estrogen are associated with the lowest risk of venous thrombosis [blood clots] and are therefore the safest option," says Astrid van Hylckama Vlieg, PhD, a research fellow at Leiden University Medical Center in the Netherlands, and the lead author of one study.

''Our study shows that there is indeed a difference in the risk of venous thrombosis associated with different types of progestins and different doses of estrogens available in the contraceptive," she tells WebMD in an email interview.

Similar results were obtained in the second study, evaluating Danish women. Both studies are published in the online edition of BMJ.

Even with differences in risk, however, a U.S. expert who reviewed the studies for WebMD points out that the differences are small and the overall risk of getting a blood clot from the pill is very low to begin with.

The risk of blood clots associated with birth control pill use has been known for decades, with several studies finding a twofold to sixfold increased risk with the use of oral contraceptives. The new research confirms earlier findings and adds new specifics about which hormones carry the most risk.

Birth Control Pills and Blood Clots

Van Hylckama Vlieg and colleagues compared 1,524 women, ages 18 to 50, diagnosed with a first deep venous thrombosis (DVT) of the leg, which is a blood clot in the leg, or a pulmonary embolism, a blood clot in the lung, and compared them with 1,760 healthy people.

Women taking oral contraceptives had a fivefold increased risk of blood clots compared with nonusers, and the risk differed by the type of progestin. "The newer types of oral contraceptives containing drospirenone or cyproterone acetate are associated with an increased risk compared with oral contraceptives containing levonorgestrel," Van Hylckama Vlieg says. Specifically, the researchers found that:

  • Levonorgestrel boosted the risk of blood clots by nearly fourfold compared to nonusers.
  • Gestodene boosted risk by 5.6 times.
  • Drospirenone boosted risk 6.3 times.
  • Cyproterone boosted risk 6.8 times.
  • Desogestrel boosted risk 7.3 times.

The risk of blood clots was also associated with the level of estrogen in the pills, with higher estrogen dose linked with higher risk.

In the national Danish study, researchers evaluated the risk of blood clots among healthy Danish women, ages 15 to 49, who were using various types of birth control pills from 1995 to 2005.

During that period, they observed 4,213 blood clots.

The risk decreased with duration of use and decreasing dose of estrogen. Like the Dutch researchers, the Danish team found that pills with levonorgestrel had a lower risk of blood clots than pills that contain other types of progestins. They found pills with norethisterone to be lower risk, too.

Second Opinion

The new research confirms previous findings and adds new information, says Ricardo Azziz, MD, chairman of obstetrics and gynecology at Cedars-Sinai Medical Center in Los Angeles, who reviewed the data for WebMD.

"We know that the combination pills [with estrogen and a progestin] do increase the risk of thrombosis," he says. It's also known, he says, that women with an inherited clotting disorder are at higher risk for having a clot if they take the pill.

But, he adds, overall ''the chances of any woman taking birth control pills having a deep vein thrombosis is low. Of 10,000 women using the pill, in one year's time six will have a deep vein thrombosis."

What's also known, he says, is "the longer you use it the less chance of having a DVT." That might be due to what experts call "selection bias" -- women who had a problem discontinued using the pill and those who remain on it are simply less prone to blood clotting problems.

What is also important to understand, Azziz says, is that even if the risk of blood clots from one type of pill is twice or more that of another, "We are talking about twice the risk for something that is quite rare to begin with."

Women shouldn't go off the pill based solely on the new findings, he says. What is crucial, he says, is for a woman's doctor to prescribe the birth control pill that's best for her, the one that will be linked with the least side effects. "Some patients will do better on some pills than others," he says.

Starting with the lower-dose estrogen pills and the ones with progestins found linked with the least risk is wise, he says. To start with, he suggests pills with levonorgesterol or norethisterone and a low dose of estrogen.

The risks associated with not taking the pill, including unwanted pregnancy and pregnancy complications, may be higher than the risk associated with its use, Azziz says.

Oliver Renner, a spokesman for Bayer Schering Pharma in Berlin, which makes oral contraceptives, says the company is in the process of evaluating the data and needs time to respond.

Show Sources


Astrid van Hylckama Vlieg, PhD, research fellow, Leiden University Medical Center, Netherlands.

Van Hylckama Vlieg, A. BMJ online edition, Aug. 14, 2009.

Lidegaard, O. BMJ online edition, Aug. 14, 2009.

Ricardo Azziz, MD, chairman of obstetrics and gynecology, Cedars-Sinai Medical Center; professor of obstetrics and gynecology and medicine, David Geffen School of Medicine, University of California, Los Angeles.

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