Blood clots have been a known risk of oral contraceptives since the 1990s, but for most women, the chances seemed small enough to justify taking the Pill. Now, in a report published in The BMJ, scientists led by Yana Vinogradova, a research fellow at the University of Nottingham, found that using the Pill was linked to anywhere from a two- to more than four-fold increased risk of developing clots compared to women who didn’t take oral contraceptives.  “Our study suggests that the newer contraceptives have a higher risk of [blood clots] than the older agents,” Vinogradova tells TIME in an email. Overall, the risk for women on the Pill was nearly three times that of women not taking the medication. The risk was highest for people taking Pills that contain newer types of the progestogen hormone, such as drospirenone, desogestrel, gestodene, and cyproterone, as compared to people taking the Pill with first-generation versions of the hormone (levonorgestrel and norethisterone).  The difference essentially boils down to the progesterone part of the drug; since the original pill was introduced in 1960, drug developers have tweaked the progesterone to lower side effects such as acne, headache, weight gain and breakthrough bleeding. But the price for those modifications may be more blood clots.  Even after Vinogradova and her team adjusted for the potential contributions of things like cancer, heart disease, varicose veins, arthritis, smoking and obesity on the risk of blood clots, the link between the newer contraceptives and increased risk remained strong.  “While [blood clots] are a relatively rare problem, they are serious and potentially avoidable with the appropriate drug choice,” says Vinogradova. “Doctors need to consider all health issues when prescribing contraceptives, selecting a drug type associated with the lowest risk for patients with particular susceptibilities.”  Whether that means that doctors should start with prescribing the older formulations first—as well non-hormonal birth control like the copper IUD—isn’t clear yet, since the newer forms have certain advantages, including the fact that they disturb the cholesterol system less, which may be important for diabetic women.  The blood clot risk, however, is something that doctors should consider when prescribing the Pill. And since there are different formulations available, Vinogradova says doctors should monitor their patients for any potential symptoms of poor circulation and switch to other formulations if needed.
A new study puts a number on the risk of developing potentially fatal blood clots after using the pill