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

Marinka S. Post, Jan Rosing, Marius J. Van der Mooren, Sonja Zweegman, W. Marchien Van Baal, Peter Kenemans, Coen D.A. Stehouwer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 17beta-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.
Original languageEnglish
Pages (from-to)1017-1023
Number of pages7
JournalBritish Journal of Haematology
Volume119
Issue number4
DOIs
Publication statusPublished - 2002

Cite this

Post, Marinka S. ; Rosing, Jan ; Van der Mooren, Marius J. ; Zweegman, Sonja ; Van Baal, W. Marchien ; Kenemans, Peter ; Stehouwer, Coen D.A. / Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women. In: British Journal of Haematology. 2002 ; Vol. 119, No. 4. pp. 1017-1023.
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title = "Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women",
abstract = "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 17beta-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.",
keywords = "APC resistance, Factor VIII, Factor XI, Hormone replacement therapy, Post-menopausal",
author = "Post, {Marinka S.} and Jan Rosing and {Van der Mooren}, {Marius J.} and Sonja Zweegman and {Van Baal}, {W. Marchien} and Peter Kenemans and Stehouwer, {Coen D.A.}",
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Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women. / Post, Marinka S.; Rosing, Jan; Van der Mooren, Marius J.; Zweegman, Sonja; Van Baal, W. Marchien; Kenemans, Peter; Stehouwer, Coen D.A.

In: British Journal of Haematology, Vol. 119, No. 4, 2002, p. 1017-1023.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women

AU - Post, Marinka S.

AU - Rosing, Jan

AU - Van der Mooren, Marius J.

AU - Zweegman, Sonja

AU - Van Baal, W. Marchien

AU - Kenemans, Peter

AU - Stehouwer, Coen D.A.

PY - 2002

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N2 - 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 17beta-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.

AB - 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 17beta-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.

KW - APC resistance

KW - Factor VIII

KW - Factor XI

KW - Hormone replacement therapy

KW - Post-menopausal

U2 - 10.1046/j.1365-2141.2002.03957.x

DO - 10.1046/j.1365-2141.2002.03957.x

M3 - Article

VL - 119

SP - 1017

EP - 1023

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

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ER -