The effect of 17β-estradiol on endothelial and inflammatory markers in postmenopausal women: a randomized, controlled trial

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 17β-estradiol daily plus 25 μg 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 17β-estradiol favourably affects the vascular inflammation processes as indicated by a neutral effect on hs-CRP and reduction of cell adhesion molecules.