Postmenopausal Hormone Therapy: : Differential Impact of Dose and Regimenson Hemostasis and Inflammation
Appears in the following Collection
AbstractPostmenopausal hormone therapy (HT) is currently mainly used for a limited time-period to relieve climacteric symptoms and for the prevention of osteoporosis. Over the last decade, reports have focused on adverse effects of HT, such as increased risk of cardiovascular disease (CVD), venous thrombosis (VT), and breast cancer. Several studies have shown that oral HT containing estrogen in conventional doses is associated with an increased risk of VT and an activation of coagulation. Moreover, it has recently been shown that even minor changes in clotting factors and coagulation inhibitors within normal ranges may account for such activation. The aim of this thesis was to compare the impact of four HT regimens on markers of activated coagulation and to identify potential mechanisms for activated coagulation by analyzing markers of vascular disease. In particular, we wanted to investigate whether lower dose of HT decreased impact on the markers. We have found that the four regimens had markedly different impact on markers of activated coagulation, coagulation factors, coagulation inhibitors, fibrinolytic factors, and on markers of inflammation. The conventional- and low-dose HT groups generally showed similar effects, with more pronounced effects in the conventional-dose HT group. In women with previous thrombosis, oral HT containing estradiol was associated with a marked and rapid increase in CRP, whereas transdermal treatment was not. Moreover, HT appeared to reduce levels of endothelial markers both in healthy women and in women with high risk of thrombosis. These findings are probably clinically relevant, and indicate that low-dose HT has a more favorable risk to benefit profile than conventional-dose HT. We believe that the differential effects of the regimens on coagulation and other markers reflect a differential risk of VT. Moreover, in women with high risk of thrombosis, the differential effects on CRP of oral and transdermal HT suggest that transdermal therapy is safer.
List of papers
I. Eilertsen AL, Qvigstad E, Andersen TO, Sandvik L, Sandset PM. Conventional-dose hormone therapy (HT) and tibolone, but not low-dose HT and raloxifene, increase markers of activated coagulation. Maturitas 2006; 55: 278-87.
II. Eilertsen AL, Sandvik L, Mowinckel MC, Andersen TO, Qvigstad E, Sandset PM. Differential effects of conventional and low dose oral hormone therapy (HT), tibolone, and raloxifene on coagulation and fibrinolysis. Thromb Res 2007; 120: 371-9
III. Eilertsen AL, Liestøl S, M. Mowinckel M, H. C. Hemker H.C., Sandset PM. Differential impact of conventional and low dose oral hormone therapy (HT), tibolone and raloxifene on functionality of the activated protein C system. Thromb Haemost 2007; 97: 938-43.
IV. Eilertsen AL, Sandvik L, Steinsvik B, Sandset PM. Differential impact of conventional dose and low dose hormone therapy (HT), tibolone and raloxifene on C-reactive protein (CRP) and other inflammatory markers. J Thromb and Haemost 2008; 6: 928-34
V. Eilertsen AL, Hoibraaten E, Os I, Andersen TO, Sandvik L, Sandset PM. The effects of oral and transdermal hormone replacement therapy on C-reactive protein levels and other inflammatory markers in women with high risk of thrombosis. Maturitas 2005; 52: 111-8.