Hormonal contraceptives and arterial disease: an epidemiological update

The cardiovascular safety of widely used combined hormonal contraceptives is still debated. Newer generations of oral formulations as well as non-oral contraceptives (transdermal and vaginal) have been recently evaluated in the context of cardiovascular disease. This review provides a summary of the association between combined oral contraceptives (COCs) and arterial diseases, with an emphasis on new formulations of hormonal contraceptives, as well as routes of administration. A systematic search of the Medline database was performed to find all relevant articles which included women who had widely use third generation pills, and the development of new progestins. Eligible articles published in English and reporting risk of arterial events (myocardial infarction [MI] and stroke) among users of hormonal contraceptives were reviewed. A quantitative assessment was made from included studies. Overall, current use of oral combined contraceptives increased the risk of MI and ischemic stroke (pooled OR: 1.7; 95% confidence interval [95% CI]: 1.2-2.3 and OR: 1.8; 95% CI: 1.2-2.8, respectively), but this was not associated with the risk of hemorrhagic stroke (OR: 1.1; 95% CI: 0.7-1.9). The increase in ischemic arterial disease was higher among first generation pill users compared with second or third generation pill users. In contrast, risk of ischemic arterial disease among current users of second or third generation pill was similar (p = 0.23 for MI risk and 0.99 for ischemic stroke). In conclusion, newer generation formulations of COCs, as well as the non-oral hormonal contraceptive, do not seem to be safer than second generation hormonal contraceptives.