Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study

Autor: Grigoris T. Gerotziafas, Eric Dasque, Jean-Louis Démolis, Dahlia Torchin, Karine Lacut, Annie Robert, Faiez Zannad, Tabassome Simon, Alexandra Rousseau, Christian Libersa, Ismail Elalamy
Přispěvatelé: Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie biologique [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité (RCV), Université Henri Poincaré - Nancy 1 (UHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Signalisation cellulaire, dynamique circulatoire et athérosclérose précoce (SCDCAP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Service d'Histologie-Biologie tumorale [Hôpital Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)
Rok vydání: 2009
Předmět:
Time Factors
MESH: Menopause
Administration
Oral
030204 cardiovascular system & hematology
Dydrogesterone
MESH: Estrogens
MESH: Dose-Response Relationship
Drug
MESH: Thrombin
0302 clinical medicine
Oral administration
Pharmacology (medical)
MESH: Double-Blind Method
030212 general & internal medicine
Clotting factor
MESH: Aged
MESH: Middle Aged
Estradiol
Thrombin
Middle Aged
Blood Coagulation Factors
3. Good health
Menopause
MESH: Administration
Oral
Drug Therapy
Combination
Female
MESH: Estradiol
medicine.drug
medicine.medical_specialty
medicine.drug_class
Placebo
03 medical and health sciences
Tissue factor
Double-Blind Method
Internal medicine
medicine
Humans
Aged
Pharmacology
MESH: Humans
Dose-Response Relationship
Drug
business.industry
MESH: Time Factors
MESH: Blood Coagulation Factors
Estrogens
medicine.disease
MESH: Drug Therapy
Combination
Endocrinology
Estrogen
MESH: Progestins
MESH: Dydrogesterone
Progestins
business
MESH: Female
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Fundamental and Clinical Pharmacology
Fundamental and Clinical Pharmacology, Wiley, 2010, 24 (2), pp.239-45. ⟨10.1111/j.1472-8206.2009.00747.x⟩
ISSN: 1472-8206
0767-3981
DOI: 10.1111/j.1472-8206.2009.00747.x⟩
Popis: International audience; Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P
Databáze: OpenAIRE
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