Newer versions of the Pill may raise a woman’s risk of dangerous blood clots even more than older versions, a large U.K. study suggests. 

Women taking any combined oral contraceptive pills - containing both estrogen and progestin - were three times as likely to develop a blood clot in a deep vein in the leg or pelvis, compared to women not on the Pill. The risk was higher still with all the newer Pill versions except one, researchers found.

“This association is between 1.5 and 1.8 times higher for the newer formulations,” said lead author Yana Vinogradova, a research fellow in medical statistics at the University of Nottingham.

The blood clots, known as venous thromboembolisms (VTEs), are common and can be deadly if the clot dislodges and travels to the heart, brain or lungs. They are more common among women taking estrogen medicines, and the risk is even higher if the woman smokes, according to the National Library of Medicine.

But the overall risk of a blood clot for women on any combined oral contraceptives is still relatively low: between six and 14 extra cases per year per 10,000 women taking the drugs, Vinogradova told Reuters Health by email.

Newer combined pills, including the progestins drospirenone, desogestrel, gestodene or cyproterone acetate, have been suspected of carrying an even higher clot risk compared to older versions that include levonorgestrel and norethisterone. But most past studies have been small or flawed by not taking into account certain other risk factors for clots, the study team writes in BMJ.

To assess VTE risk in women on both older and newer-generation pills, the researchers analyzed U.K. general practice databases covering the period between 2001 and 2013. They found 5,062 cases of VTE among women ages 15 to 49, and matched each of these women with up to five women who did not have a blood clot in the same year, but were of similar age and treated at a similar medical practice.

The researchers accounted for smoking, alcohol consumption, race, body mass index and other health problems, and found that women taking any combined oral contraceptive were almost three times as likely to suffer a blood clot as those not taking contraceptive pills.

Women taking older-generation drugs were about 2.5 times as likely to have a blood clot as women not taking any oral contraceptives over the previous year. Those taking newer types of combined pills were about four times as likely to suffer a clot compared to women not taking oral contraceptives.

The exception among the newer formulations was norgestimate, with a risk profile more similar to the older drugs.

The results would translate to a number of “extra” cases of VTE among women taking the combined pills versus women not on the Pill. These numbers were lowest for the older drug levonorgestrel and the newer norgestimate, with an additional six cases per 10,000 women per year, and highest for two newer drugs, desogestrel and cyproterone, with an extra 14 cases each.

“However,” Vinogradova noted, "these increased risks of (venous thromboembolism) associated with both the older and the newer pills are lower than those associated with pregnancy,” which may increase clot risk tenfold.

The newer pills carry higher clot risk, but were introduced as potentially having new benefits as well, including reduced acne, headache, depression, weight-gain, breast symptoms and breakthrough bleeding, she said.

The association between different oral contraceptives and blood clot risk has been controversial and previous study results have been mixed, but the new findings help to clarify those inconsistencies, Susan Jick, a professor at Boston University School of Public Health wrote in an editorial accompanying the new results.

About nine percent of women worldwide take birth control pills, including 28 percent of women in the U.K., the authors write.

Any women who are concerned should discuss treatment options with their doctor at their next routine appointment, Vinogradova said.

“Some women are at higher risk of (blood clot) because of family history or other medical conditions and doctors will already take account of these factors when advising women regarding their options for contraception,” she said.