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.

Plu-Bureau G ，Maitrot-Mantelet L ，Hugon-Rodin J ，Canonico M ... -  《-》

Epidemiology of hormonal contraceptives-related venous thromboembolism.

For many years, it has been well documented that combined hormonal contraceptives increase the risk of venous thromboembolism (VTE). The third-generation pill use (desogestrel or gestodene (GSD)) is associated with an increased VTE risk as compared with second-generation (levonorgestrel) pill use. Other progestins such as drospirenone or cyproterone acetate combined with ethinyl-estradiol (EE) have been investigated. Most studies have reported a significant increased VTE risk among users of these combined oral contraceptives (COCs) when compared with users of second-generation pills. Non-oral combined hormonal contraception, such as the transdermal patch and the vaginal ring, is also available. Current data support that these routes of administration are more thrombogenic than second-generation pills. These results are consistent with the biological evidence of coagulation activation. Overall, the estrogenic potency of each hormonal contraceptive depending on both EE doses and progestin molecule explains the level of thrombotic risk. Some studies have shown a similar increased VTE risk among users of COCs containing norgestimate (NGM) as compared with users of second-generation pill. However, for this combination, biological data, based on quantitative assessment of sex hormone-binding globulin or haemostasis parameters, are not in agreement with these epidemiological results. Similarly, the VTE risk associated with low doses of EE and GSD is not biologically plausible. In conclusion, newer generation formulations of hormonal contraceptives as well as non-oral hormonal contraceptives seem to be more thrombogenic than second-generation hormonal contraceptives. Further studies are needed to conclude on the combinations containing NGM or low doses of EE associated with GSD.

Hugon-Rodin J ，Gompel A ，Plu-Bureau G 《-》

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.

Plu-Bureau G ，Hugon-Rodin J ，Maitrot-Mantelet L ，Canonico M ... -  《-》

Thrombotic risks of oral contraceptives.

Rott H 《-》

Combined hormonal contraception and venous thromboembolism.

Martínez F ，Avecilla A 《EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE》