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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1660.)
© 2006 American Heart Association, Inc.

Thrombosis

Less Effect of Intranasal Than Oral Hormone Therapy on Factors Associated With Venous Thrombosis Risk in Healthy Postmenopausal Women

Majoie Hemelaar; Jan Rosing; Peter Kenemans; M. Christella L.G.D. Thomassen; Didi D.M. Braat; Marius J. van der Mooren

From the Project "Aging Women" and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, the Netherlands (M.H., P.K., M.J.v.d.M.), and Radboud University Nijmegen Medical Centre, Nijmegen (D.D.M.B.), the Netherlands; and Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands (J.R., M.C.L.G.D.T.).

Correspondence to M.J. van der Mooren, Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, 1081 HV, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail mj.vandermooren{at}vumc.nl

Objective— To compare the effects of intranasal and oral administration of 17ß-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.

Methods and 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 µg/275 µg 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.

Conclusion— 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.

This randomized, double-blind clinical trial in 90 healthy postmenopausal women compared the effects of intranasal E₂/NET and oral E₂/NETA therapy on nAPCsr and on other hemostatic parameters associated with venous thrombosis. Effects in the intranasal group were smaller than in the oral group, which may suggest a lower venous thrombosis risk.

Key Words: APC resistance • hormone therapy • intranasal • menopause • norethisterone • venous thrombosis