Hormonal contraceptives and venous thromboembolism: an epidemiological update

Since the early 1960s, it has been well documented that combined hormonal contraceptives increase the risk of cardiovascular disease. Newer generation of oral formulations, as well as non-oral contraceptives (transdermal and vaginal), have been recently studied for thrombotic risk. This review provides a summary of the association between hormonal contraceptives and venous thromboembolism with emphasis on new formulations of hormonal contraceptives as well as route of administration. A systematic search of Medline database was done for all relevant articles which included women having used third generation pills, and the development of new progestins. Eligible articles published in English and reporting the risk of venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis) among users of hormonal contraceptives were reviewed. A quantitative assessment was made from included studies. Current use of drospirenone or cyproterone oral combined contraceptives increased the risk of VTE compared with second generation pills (pooled OR: 1.7; 95% confidence interval [95% CI]: 1.4-2.2 and OR: 1.8; 95% CI: 1.4-2.3, respectively). In the context of contraceptive use, non-oral route of ethinyl-estradiol administration seems to be more thrombogenic than oral route. In contrast, low doses of both oral progestin contraceptives and intrauterine levonorgestrel could be safe with respect to VTE risk. In conclusion, newer generation formulations of hormonal contraceptives, as well as the non-oral hormonal contraceptive, seem to be more thrombogenic than second generation hormonal contraceptives.