Volume 119, Issue 4 pp. 1017-1023

Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women

Marinka S. Post

Marinka S. Post

Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,

Search for more papers by this author
Jan Rosing

Jan Rosing

Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, and Departments of

Search for more papers by this author
Marius J. Van Der Mooren

Marius J. Van Der Mooren

Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,

Search for more papers by this author
Sonja Zweegman

Sonja Zweegman

Haematology and

Search for more papers by this author
W. Marchien Van Baal

W. Marchien Van Baal

Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,

Search for more papers by this author
Peter Kenemans

Peter Kenemans

Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,

Search for more papers by this author
Coen D. A. Stehouwer

Coen D. A. Stehouwer

Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

Search for more papers by this author
First published: 11 December 2002
Citations: 30
Prof. Dr C. D. A. Stehouwer, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 mol/LB Amsterdam, The Netherlands. E-mail: [email protected]

Abstract

Summary. As hormone replacement therapy is associated with an early excess risk of venous thrombosis, we investigated the effect of different oral hormone replacement therapies on resistance to activated protein C, and on levels of factor VIII antigen (FVIII:Ag) and factor XI antigen (FXI:Ag). In a prospective, randomized, placebo-controlled 12-week study, 60 healthy post-menopausal women daily received either placebo (n = 16) or 2 mg of micronized 17β-oestradiol, either alone (E2, n = 16) or sequentially combined with dydrogesterone 10 mg (E2 + D, n = 14) or trimegestone 0·5 mg (E2 + T, n = 14). Medication was given orally. Normalized activated protein C sensitivity ratios (nAPCsr) were determined by quantifying the effect of activated protein C on the endogenous thrombin potential. FVIII:Ag and FXI:Ag were determined by enzyme-linked immunosorbent assay. Compared with baseline and placebo, the nAPCsr increased (92% to 142%; all P < 0·001) in all active treatment groups after both 4 and 12 weeks. Compared with placebo, hormone replacement therapy was not associated with significant changes in FVIII:Ag. After 4 and 12 weeks, FXI:Ag levels were significantly decreased in the E2 group (mean percentage changes from baseline versus placebo: −15·0%, P = 0·001 at 4 weeks and −16·6%, P = 0·003 at 12 weeks) and in the E2 + D group (−10·4%, P = 0·02 and −10·4%, P = 0·02). In conclusion, all hormone replacement regimens were associated with a large increase in resistance to activated protein C. In contrast, hormone replacement therapy had no effect on FVIII:Ag. Oral E2 and E2 + D had a small, favourable effect on FXI:Ag.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.