La voie d'administration (orale versus transdermique) joue-t-elle un rôle dans le risque d'événements thromboemboliques associés aux thérapies hormonales ? Comparaison entre les thérapies hormonales de substitution et les thérapies hormonales contraceptives

Details

Supervisors

Douxfils, Jonathan ; Morimont, Laure

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences pharmaceutiques, à finalité spécialisée

Abstract

enThe aim of this work is to compare the thromboembolic risks induced by the route of administration (oral versus transdermal) in contraceptive and hormone replacement therapies. In order to do so, it was necessary to provide some background information on the female hormonal cycle and on the hormonal therapies available on the market in pill and transdermal patch form. Both hormonal preparations consist of an estrogenic and/or progestin derivative. In general, contraceptives contain ethinylestradiol and hormone replacement therapies contain estradiol. Once the theoretical knowledge was acquired, the study of the pharmacological properties of estrogens and progestins allowed the hormonal potency of estrogens and the estrogenicity of each hormonal therapy to be defined. On the other hand, pharmacokinetic analysis shows that only the metabolisation phase is really impacted by the route of administration (oral or transdermal). When taking hormonal therapy, the haemostatic balance is disrupted as a result of changes in the levels of haemostatic variables leading to a state of hyper-coagulability. In hormonal contraceptives, this risk is similar regardless of the route of administration. Conversely, oral administration of hormone replacement therapy induces a higher thromboembolic risk than transdermal administration. Therefore, the route of administration plays a role in the thromboembolic risk associated with hormone replacement therapy, not contraceptive therapy. An assessment of this risk can be made using tests (thrombin generation test and activated partial thromboplastin time) or biomarkers (SHBG, CBG, angiotensinogen and coagulation markers). In conclusion, the risk of developing venous thromboembolism depends on the composition of the hormone therapy. A new esterol-based therapy (in clinical trials) would seem to avoid this thromboembolic risk and could therefore provide a solution to the problem.