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Thromb Haemost 2007; 97(06): 938-943
DOI: 10.1160/TH06-11-0632
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Differential impact of conventional and low-dose oral hormone therapy (HT), tibolone and raloxifene on functionality of the activated protein C system

Anette L. Eilertsen
1   Department of Haematology Ullevål University Hospital Trust, Oslo, Norway
2   Medical Clinic, Faculty Division Ullevål University Hospital, Oslo, Norway
,
Sigurd Liestøl
1   Department of Haematology Ullevål University Hospital Trust, Oslo, Norway
,
Marie-Christine Mowinckel
1   Department of Haematology Ullevål University Hospital Trust, Oslo, Norway
,
H. Coen Hemker
3   Synapse BV, Cardiovascular Research Institute, Maastricht, The Netherlands
,
Per-Morten Sandset
1   Department of Haematology Ullevål University Hospital Trust, Oslo, Norway
2   Medical Clinic, Faculty Division Ullevål University Hospital, Oslo, Norway
› Author AffiliationsFinancial support: The RET-study was financially supported by anunconditional grant from Novo Nordisk Scandinavia. A. Eilertsenisa Research Fellow at the University of Oslo.
Further Information

Publication History

Received 07 November 2006

Accepted after resubmission 15 March 2007

Publication Date:
27 November 2017 (online)

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Summary

Recent studies have shown that hormone therapy (HT) is associated with an acquired resistance to activated protein C (APC). The aims of the present study were to evaluate a possible dose-response relationship and differential effects of different HT regimens on functionality of the APC system. Two hundred two healthy women were randomly assigned to receive treatment for 12 weeks with tablets containing either low-dose HT containing 1 mg 17β-oestradiol + 0.5 mg norethisterone acetate (NETA) (n=50), conventional-dose HT containing 2 mg 17β-oestradiol and 1 mg NETA (n=50), 2.5 mg tibolone (n=51), or 60 mg raloxifene (n=51). Normalized APC system sensitivity ratios (nAPCsr) were determined in plasma collected at baseline and after 12 weeks using a thrombin generation-based APC resistance test probed with either recombinant APC (rAPC) or thrombomodulin (rTM). NAPCsr increased in both the conventional- and low-dose HT groups, consistent with reduced sensitivity to APC. The increase was slightly more pronounced in the conventional-dose group, but the difference between the two HT groups was not statistically significant. The sensitivity to APC was only marginally altered in those allocated to tibolone. Consequently, tibolone showed a different phenotype as compared with the low-dose HT group. A small increase in nAPCsr with both rAPC and rTM was seen in the raloxifene-group, but the increase was less than in the low-dose HT group. Our findings indicate that oestrogen-progestin therapy induces an APC resistant phenotype, which may be related to dose, whereas tibolone and raloxifene only marginally alter the sensitivity to APC.

Keywords

Activated protein C - hormone therapy - tibolone - raloxifene - coagulation
 

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