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 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 ... -  《-》

Combined hormonal contraception and venous thromboembolism.

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

Thrombotic risks of oral contraceptives.

Rott H 《-》

[Hormonal contraception and vascular risk: CNGOF Contraception Guidelines].

Venous thromboembolism and arterial ischemic events are the main deleterious diseases associated with the use of combined hormonal contraceptives (CHC). Even though their composition has been substantially improved, the vascular risk persists with the most recent CHCs use. If the vascular risk associated with CHCs containing 50μg EE is significantly higher than with those containing less than 50μg, there is no evidence that the CHCs containing either 30 or 20μg of EE induce different venous risks. CHC containing gestodene, desogestrel, drospirenone or cyproterone acetate are associated with a higher risk of venous thrombosis compared with levonorgestrel-containing CHCs. CHC containing norgestimate are associated with similar venous thrombosis risk than CHC containing levonorgestrel. Venous thrombosis risk of non-oral routes of administration of CHC appears to be equivalent to the risk of CHC containing gestodene or desogestrel, but this result is based on a small number of epidemiological studies. Before prescribing a CHC, it is important to determine all vascular risk factors. Family history of ischemic arterial event or venous thromboembolism disease should be routinely sought before any CHC prescription. All CHCs are contraindicated in women with biological thrombophilia, in women with combined vascular risk factors, in women with first-degree family history of arterial or venous event (under age 50) as well as in women suffering of migraine with aura. Progestin-only contraceptives are not associated with vascular risk (arterial or venous) outside of medroxyprogesterone acetate. In women with higher vascular risk, progestin-only contraceptives (administered by oral, sous-cutaneous or intra-uterine routes) can be prescribed.

Plu-Bureau G ，Sabbagh E ，Hugon-Rodin J 《-》