Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women
Marinka S. Post
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorJan Rosing
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, and Departments of
Search for more papers by this authorMarius J. Van Der Mooren
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorW. Marchien Van Baal
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorPeter Kenemans
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorCoen D. A. Stehouwer
Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorMarinka S. Post
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorJan Rosing
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, and Departments of
Search for more papers by this authorMarius J. Van Der Mooren
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorW. Marchien Van Baal
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorPeter Kenemans
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam,
Search for more papers by this authorCoen D. A. Stehouwer
Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorAbstract
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.
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