Combined hormonal oral contraception and risk of venous thromboembolism (VTE)
WHO produces a series of evidence-based family planning guidelines aimed at national policy makers and programme managers that are designed to promote access to and quality of family planning services for clients. The Medical Eligibility Criteria for Contraceptive Use (MEC) provides guidance regarding “who” can use contraceptive methods safely, and the Selected Practice Recommendations for Contraceptive Use (SPR) provide guidance on “how” to use various methods safely and effectively. In effect, these two documents provide evidence-based guidance on choosing and using contraceptive methods. WHO is in the process of updating these documents, with a goal for finalizing them in 2014.
Since the publication of the last editions of these documents in 2008, a variety of groups, including the United States Food and Drug Administration (US FDA) and the European Medicines Agency (EMA), have undertaken reviews of a number of studies examining the risk of venous thromboembolism (VTE) among women using combined hormonal contraceptives with different types of progestogens. These reviews have consistently concluded that, although there may be differences in venous thromboembolism risk between products with different progestogens, the absolute risks are very small.
In August 2012, the US FDA issued a safety communication which stated that “drospirenone-containing birth control pills may be associated with a higher risk for blood clots than other progestin-containing pills” but emphasised that the available epidemiologic studies showed conflicting results, and other factors may have accounted for the differences; a causal relationship was not clear. The US FDA also underlined that “the risk of blood clots is higher when using any birth control pills than not using them, but still remains lower than the risk of developing blood clots in pregnancy and the postpartum period.”
Factors to consider when choosing a particular contraceptive method include the characteristics of the potential user, the background risk of disease, safety and adverse effect profiles of different products, cost, availability, and patient preferences.
In February 2013, the EMA started a new review of all available data on the risk of VTE and arterial thromboembolism with several combined hormonal contraceptives containing the following progestogens: chlormadinone, desogestrel, dienogest, drospirenone, etonogestrel, gestodene, nomegestrol, norelgestromin and norgestimate. An update from the EMA on the use of these products is expected in October 2013.
Separately, the EMA conducted a review on the use of Diane 35 (cyproterone acetate 2 mg, ethinylestradiol 35 micrograms) and its generics. The EMA reminded prescribers that these preparations should only be used for the treatment of moderate to severe acne related to androgen sensitivity or hirsutism in women of reproductive age. Although the preparations also prevent conception this is not their main purpose. It is essential that Diane 35 and its generics are not used with hormonal contraception.
As with all licensed medicines, combined hormonal contraceptives are continuously monitored by the licensing authorities, who work to ensure that healthcare professionals and women have access to the best possible information on the risks and the benefits of these medicines to allow them to make the best choice for their contraception. Factors to consider when choosing a particular contraceptive method include the characteristics of the potential user, the background risk of disease, safety and adverse effect profiles of different products, cost, availability, and patient preferences.
The World Health Organization (WHO) convened a series of technical consultations between 13 and 16 May 2013 in order to plan the updates of both the MEC and SPR. As part of the process for updating these guidelines, WHO will be considering the evidence related to VTE risk associated with oral contraceptive formulations with various progestogens. Once this process has been completed, WHO will be in a position to provide global guidance on this issue.
However, at this time, there is no need to change existing practices and the conclusions reached by medicines regulatory authorities can be used by health professionals and their clients when making informed choices between alternative contraceptive options.
- World Health Organization. Medical Eligibility Criteria for Contraceptive Use, 4th ed. Geneva: WHO; 2008.
- World Health Organization. Selected Practice Recommendations for Contraceptive Use, 3rd ed. Geneva: WHO; 2008.
- United States Food and Drug Administration. (2012). Updated information about the risk of blood clots in women taking birth control pills containing drospirenone [Safety communication] Retrieved from http://www.fda.gov/Drugs/DrugSafety/ucm299305.htm
- European Medicines Agency. (2013). Benefits of Diane and generics outweigh risks in specific patient group, PRAC recommends measures to minimize risks of thromboembolism [Press release] Retrieved from http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/05/news_detail_001790.jsp&mid=WC0b01ac058004d5c1