Newer versions of the pill raise the risk of serious blood clots compared with older combined oral contraceptives, a new analysis has found, which also confirms a previously established link to venous thromboembolism.

The study, published in The BMJ, found that, relative to non-use, the risk of this clotting was about 2.5 times higher with older oral contraceptives - but higher still, around 3.6- to 4.3-fold, with newer contraceptives.

Pills containing one of the newer types of progestogen hormone - drospirenone, desogestrel, gestodene or cyproterone - were associated with an increased risk of venous thromboembolism (VTE) versus pills containing older progestogens - levonorgestrel and norethisterone.

The UK researchers based at the University of Nottingham describe their study as “an important clarifying” one that “has sufficient power to provide reliable comparative findings for different formulations of combined oral contraceptives.”

The yearly number of extra VTE cases per 10,000 women was lowest for levonorgestrel and norgestimate - six extra cases - and highest for desogestrel and cyproterone - 14 extra cases.

Overall, this meant the relative risks for women using newer pills were estimated to be 1.5 to 1.8 times higher than for women using older pills.

The researchers “stress that oral contraceptives are remarkably safe” and put some perspective on the relative risk represented by the small absolute number of extra cases, whether from using a newer or older one.

They say that the reported three times increased risk of VTE in their study, in women using oral contraceptives, is still lower than the up to 10-fold increased risk of VTE seen in pregnant women.

The researchers cite that, worldwide, about 9% of women in the relevant age group use oral contraceptives. In developed countries specifically, the proportion is 18% of women, and in the country analyzed by the researchers, the UK, 28%.

Study brings clarification on pill risk

The researchers were led by Yana Vinogradova, research fellow in medical statistics at the University of Nottingham. Two large UK general practice databases were mined for prescription data so that the statisticians could measure associations between pill use and VTE in women between the ages of 15 and 49 years. Adjustments were made to take account of other known risk factors.

The study identified over 10,500 cases of VTE and around 42,000 matched controls. It was an observational study so a question of cause and effect could not be answered definitely.

Although the increased clot risk associated with combined oral contraceptives is well known from previous studies, the new research did not have their limitations to identifying different combinations’ relative risks, which had been inconclusive before.

An editorial article in the same issue of The BMJ commenting on the study says its results, combined with those from a similar study in 2011, “clarify inconsistencies in earlier studies and provide important guidance for the safe prescribing of oral contraceptives.”

In April, we reported figures from the Centers for Disease Control and Prevention (CDC) showing a rise in IUD and contraceptive implant use among US teens.

The longest term recommended by the US regulator for keeping contraceptive implants in place is 3 years, and 5 years for hormonal intrauterine devices (IUDs), but a study published in February found they may remain effective a year after these expiry dates.

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Written by Markus MacGill