Combined contraceptive pills containing one of the newer progestogens are associated with a higher risk of venous thromboembolism (VTE) than pills containing older progestogens, a study published in The BMJ
on 26 May 2015 has found.
The increased clot risk associated with combined oral contraceptives is well known, but previous studies have used different methods to examine this link, meaning the relative risks associated with different hormone combinations have been unclear.
To address this, researchers from the University of Nottingham used prescription data from two large UK general practice databases to measure the associations between use of different types of combined oral contraceptives and risk of VTE in women aged 15-49 years, adjusting for other known risk factors. A total of 1,340 practices were covered by the two databases from which 10,562 eligible VTE cases were identified and matched with 42,034 controls.
The results showed that current users of any combined oral contraceptive had a threefold increased risk of VTE compared with non-users of similar age and health status (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17).
When different pill combinations were looked at, women using combined pills containing older progestogens (levonorgestrel, norethisterone and norgestimate) had around a two and a half times increased risk of VTE compared with women not using any form of pill, while women using pills containing newer progestogens (drospirenone, desogestrel, gestodene and cyproterone) had around a four times increased risk of VTE.
In absolute terms, the number of extra VTE cases per year per 10,000 treated women was lowest for levonorgestrel and norgestimate (six extra cases), and highest for desogestrel and cyproterone (14 extra cases).
Around 28% of women in the UK use oral contraceptive pills and the authors stress that combined contraceptive pills are remarkably safe, emphasising that the three times increased risk of VTE in women using oral contraceptives reported in their study is far lower than the ten-fold increased risk of VTE in pregnant women.
Yana Vinogradova, research fellow in medical statistics at the University of Nottingham, says women on combined contraceptive drugs “should not stop using them, but should consult their doctor and review their current type of pill at their next appointment if they have any concerns”.
In an accompanying editorial
, Susan Jick, a professor of epidemiology at Boston University school of public health, says the 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”.
These results, in addition to those of a similar Danish study
published in 2011, “clarify inconsistencies in earlier studies and provide important guidance for the safe prescribing of oral contraceptives,” she adds.
Valerie Beral, professor of epidemiology and director of the cancer epidemiology unit at the University of Oxford, says: “There is nothing new about these findings – they just confirm what we have known for more than two decades now. The MHRA [Medicines and Healthcare products Regulatory Agency] have prescribing guidelines directly relevant to the issue, which already incorporate previous evidence, and which were updated quite recently.”
Helen Stokes-Lampard, from the Royal College of GPs, says: “The second generation combined oral contraceptive pill is associated with a slightly lower risk of complications of thromboembolism than the newer, third generation pills. But this must be kept in perspective as the newer pills have some other advantages over second generation pills in terms of fewer side effects, so a decision specific to that patient’s needs and her previous experiences should be made.”
 Vinogradova Y, Coupland C & Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. The BMJ 2015;350:h2135. doi:10.1136/bmj.h2135.
 Jick SS. Fresh evidence confirms links between newer contraceptive pills and higher risk of venous thromboembolism: important insights for women and their doctors. The BMJ 2015;350:h2422. doi:10.1136/bmj.h2422.
 Lidegaard O, Nielson LH, Skovlund CW et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study 2001-9. The BMJ 2011;343:d6423.