Birth control pills are generational; the first generation of pills in the 1960s were added with so much estrogen they were believed to increase a woman’s risk for venous thromboembolism (VTE), or blood clots, by nine times. While second, third, even fourth generation pills were added with different, safer doses of hormones, including drospirenone and desogestrel, there may still be risk for VTE if women combine pills from different generations.

Researchers from the University of Nottingham in the UK found the studies investigating the association between hormonal contraception and blood clots rely on different methods, making it hard to conclude the relative risks. To change that, researchers adjusted for known risk factors when analyzing prescription data previously collected by two of the UK’s general practice databases. Their sample size included women ages 15 to 49 years old with no records of VTE prior to the start of their respective studies.

The data included all the most commonly used contraceptives in the UK: norethisterone, levonorgestrel, norgestimate, desogestrel, gestodene, and drospirenone, plus cyproterone, a hormonal treatment for acne. Researchers factored in prescriptions issued in the last year, any previous drug use, exposure duration (since VTE is likely to be highest in the first three months of use), length of duration, in addition to cofounding variables, such as polycystic ovary syndrome, alcohol consumption, and social deprivation.

Compared to women not taking oral contraceptives, women using older pills containing levonorgestrel, norethisterone, and norgestimate were two and a half times more likely to develop VTE compared with women not using oral contraceptives — a risk that nearly doubles when women using newer pills containing drospirenone, desogestrel, gestodene, and cyproterone. Generally, women using newer pills were up to 1.8 times more likely to develop VTE.

In an accompanying editorial, Professor Susan Jick, of Boston University School of Public Health, said this study “addresses important questions about the risk of [VTE] in women taking oral contraceptives, concluding that the risk is around twofold higher than the risk associated with older contraceptives.” The researchers, though, did make a point to say women combining generations of birth control should not stop using them. They should, however, consult their doctor and review their current prescription in order to address any concerns.

That this is an observational study means there’s still no definitive answer on whether or not birth control causes VTE. It does clarify existing data and provides “important guidance for the safe prescribing of oral contraceptives.”

Source: Vinogradova Y, Coupland C, and Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2015.