title: Increased thrombin generation among postmenopausal women using hormone therapy: importance of the route of estrogen administration and progestogens.
abstract: OBJECTIVE
  Increased thrombin generation has emerged as a new surrogate marker of venous thromboembolism. Using calibrated automated thrombography, we tested the influence of the route of estrogen administration and progestogens on thrombin generation among postmenopausal women using hormone therapy.
  
  
  METHODS
  Baseline thrombin generation, together with clotting factors and inhibitors, was determined in plasma from 115 healthy postmenopausal women. Women were classified by the use of hormone therapy into three groups: nonusers (n = 38), users of oral estrogens (n = 38), and users of transdermal estrogens (n = 39).
  
  
  RESULTS
  Oral estrogens dose dependently increased thrombin generation. Thrombin generation was increased among users of transdermal estrogens combined with progestins but was similar to nonusers among women using transdermal estrogens plus progesterone. Prothrombin was the main determinant of thrombin generation and explained a part of these differences. However, single clotting factors and inhibitors contributed little to the hormone-related changes in thrombin generation.
  
  
  CONCLUSIONS
  Increased thrombin generation can be detected in women using hormone therapy, but this hypercoagulable phenotype depends both on the route of estrogen administration and the type of progestogens. These findings are consistent with current data on the risk of venous thromboembolism related to hormone therapy.
authors.affiliation: Inserm and University Paris XI, CESP Centre for Research in Epidemiology and Population Health, UMR-S 1018, Team 08: "Hormones and Cardiovascular Disease, Villejuif, France. pierre-yves.scarabin@inserm.fr
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Scarabin
authors.forename: H Coen
authors.initials: HC
authors.lastname: Hemker
authors.forename: Céline
authors.initials: C
authors.lastname: Clément
authors.forename: Véronique
authors.initials: V
authors.lastname: Soisson
authors.forename: Martine
authors.initials: M
authors.lastname: Alhenc-Gelas
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012307:Risk Factors; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism*; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D004967:Estrogens; D011372:Progestins; D013917:Thrombin