title: Less effect of intranasal than oral hormone therapy on factors associated with venous thrombosis risk in healthy postmenopausal women.
abstract: OBJECTIVE
  To compare the effects of intranasal and oral administration of 17beta-estradiol (E2) and norethisterone(acetate) [NET(A)] in healthy postmenopausal women on activated protein C (APC) resistance and other hemostatic parameters associated with venous thrombosis.
  
  
  RESULTS
  In this 2-center, randomized, double-blind, 1-year trial, 90 postmenopausal women (56.6+/-4.7 years of age) received daily either an intranasal spray with 175 microg/275 microg E2/NET (n=47) or 1 mg/0.5 mg oral E2/NETA (n = 43). Normalized APC sensitivity ratios (nAPCsr) were determined with a thrombin generation-based APC resistance test. After 1 year, the increase in nAPCsr was smaller in the intranasal than in the oral group: 11% (95% CI, 1% to 22%) versus 53% (95% CI, 37% to 72%). Overall, the decrease in antithrombin and increase in prothrombin fragment 1+2 (F1+2) were smaller and the decrease in free protein S larger in the intranasal compared with the oral group after 1 year. In both groups, the decreases in protein C and prothrombin, and the increase in d-dimer were similar.
  
  
  CONCLUSIONS
  Compared with oral E2/NETA therapy, intranasal administration of E2/NET had less effect on APC resistance and on a number of other parameters associated with venous thrombosis. This observation suggests the possibility of a lower venous thrombosis risk for intranasal E2/NET compared with oral therapy.
authors.affiliation: Project Aging Women and Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, 1081 HV, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Majoie
authors.initials: M
authors.lastname: Hemelaar
authors.forename: Jan
authors.initials: J
authors.lastname: Rosing
authors.forename: Peter
authors.initials: P
authors.lastname: Kenemans
authors.forename: M Christella L G D
authors.initials: MC
authors.lastname: Thomassen
authors.forename: Didi D M
authors.initials: DD
authors.lastname: Braat
authors.forename: Marius J
authors.initials: MJ
authors.lastname: van der Mooren
mesh_terms: D020016:Activated Protein C Resistance / Q000503:physiopathology; D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000991:Antithrombins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D006487:Hemostasis; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000097:blood; D017293:Protein S / Q000378:metabolism; D011516:Prothrombin; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000991:Antithrombins; D010446:Peptide Fragments; D017293:Protein S; C045879:prothrombin fragment 1.2; D004958:Estradiol; D011516:Prothrombin; D009640:Norethindrone