Stefan Störk1, Clemens von Schacky, Peter Angerer. 1. Medizinische Klinik, Klinikum der Ludwig-Maximilians Universität München-Innenstadt, München, Germany. s.stoerk@medizin.uni-wuerzburg.de
Abstract
BACKGROUND: Intervention trials in postmenopausal women with coronary artery disease have failed to demonstrate beneficial effects of hormone replacement therapy (HRT) on the course of disease, potentially due to pro-inflammatory effects of conjugated equine estrogens. We characterized the effects of 48 weeks treatment with two estradiol-based HRT regimens on nonspecific (high sensitivity C-reactive protein [hs-CRP], blood sedimentation rate [BSR], fibrinogen) and specific endothelial markers (cell adhesion molecules: ICAM-1, VCAM-1, E-selectin). METHOD AND RESULTS:Postmenopausal women randomly received either 1 mg 17beta-estradiol daily plus 25 microg gestodene for the last 12 days of each 28 day cycle (=standard dose progestin; n=65), or gestodene added each third cycle only (=low dose progestin; n=65), or no HRT (n=73). Both HRT regimens reduced levels of ICAM-1 (-9%), VCAM-1 (-9%), E-selectin (-11%), fibrinogen (-12%), BSR (-5%). No effect was observed on hs-CRP levels in any group. In smokers, E-selectin remained unchanged whereas ICAM-1 and VCAM-1 were lowered. Subjects on antihypertensive or lipid lowering medication showed effects comparable to the whole cohort. Effects of low and standard dose progestin were not different. CONCLUSION: We conclude that a combination therapy with 1 mg 17beta-estradiol favourably affects the vascular inflammation processes as indicated by a neutral effect on hs-CRP and reduction of cell adhesion molecules.
RCT Entities:
BACKGROUND: Intervention trials in postmenopausal women with coronary artery disease have failed to demonstrate beneficial effects of hormone replacement therapy (HRT) on the course of disease, potentially due to pro-inflammatory effects of conjugated equine estrogens. We characterized the effects of 48 weeks treatment with two estradiol-based HRT regimens on nonspecific (high sensitivity C-reactive protein [hs-CRP], blood sedimentation rate [BSR], fibrinogen) and specific endothelial markers (cell adhesion molecules: ICAM-1, VCAM-1, E-selectin). METHOD AND RESULTS: Postmenopausal women randomly received either 1 mg 17beta-estradiol daily plus 25 microg gestodene for the last 12 days of each 28 day cycle (=standard dose progestin; n=65), or gestodene added each third cycle only (=low dose progestin; n=65), or no HRT (n=73). Both HRT regimens reduced levels of ICAM-1 (-9%), VCAM-1 (-9%), E-selectin (-11%), fibrinogen (-12%), BSR (-5%). No effect was observed on hs-CRP levels in any group. In smokers, E-selectin remained unchanged whereas ICAM-1 and VCAM-1 were lowered. Subjects on antihypertensive or lipid lowering medication showed effects comparable to the whole cohort. Effects of low and standard dose progestin were not different. CONCLUSION: We conclude that a combination therapy with 1 mg 17beta-estradiol favourably affects the vascular inflammation processes as indicated by a neutral effect on hs-CRP and reduction of cell adhesion molecules.
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