Short-term hormone replacement therapy: reduced plasma levels of soluble adhesion molecules.
BACKGROUND
Epidemiological data have suggested that the use of hormone replacement therapy (HRT) is associated with a decreased risk of cardiovascular disease. Vascular endothelium and adhesion molecules play an important role in the initiation and progression of atherosclerosis.


METHODS
Prospective, randomized, placebo-controlled 12-week study. Sixty healthy, normotensive postmenopausal women received either micronised oestradiol 2 mg alone (n = 16, E2 group), or sequentially combined with a progestagen; E2 + P groups trimegestone 0.5 mg (E2 + T, n = 14) or dydrogesterone 10 mg (E2 + D group, n = 14) or placebo (n = 16). Data were collected at baseline and at 4 and 12 weeks.


RESULTS
Twelve weeks of treatment with E2 or E2 + P was associated with a significant decrease in the plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and thrombomodulin (sTM). The average decrease in these markers was about 9%. In women treated with trimegestone the decreases were larger than in those treated with dydrogesterone; for sICAM-1 (-15% vs. -2%; P < 0.0001), sVCAM-1 (-15% vs. +3%; P = 0. 003) and sTM (-9% vs. -4%; P = 0.11). Plasma levels of endothelin-1 (ET-1) decreased (by 13%) only in women treated with E2 + P. In the E2 group, flow-mediated, endothelium-dependent vasodilatation increased by 6 percentage points after 12 weeks (P = 0.07 vs. baseline, P = 0.02 vs. E2 + P, and P = 0.17 vs. placebo).


CONCLUSIONS
Short-term treatment with E2 or E2 + trimegestone reduces plasma levels of sICAM-1, sVCAM-1 and sTM. ET-1 decreased only in the E2 + P groups. Different types of progestagens may differentially affect sICAM-1, sVCAM-1 and sTM levels, which may be relevant for the choice of type HRT.
Van Baal
W M
WM
University Hospital Vrije Universiteit, Amsterdam, the Netherlands.
Emeis
J J
JJ
Kenemans
P
P
Kessel
H
H
Peters-Muller
E R
ER
Schalkwijk
C G
CG
van der Mooren
M J
MJ
Stehouwer
C D
CD
D002784:Cholesterol / Q000097:blood; D019040:E-Selectin / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010919:Placebos; D017698:Postmenopause; D011372:Progestins; D011397:Promegestone / Q000031:analogs & derivatives; D011446:Prospective Studies; D018180:Thrombomodulin / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D014664:Vasodilation / Q000187:drug effects
D019040:E-Selectin; D019332:Endothelin-1; D010919:Placebos; D011372:Progestins; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C050319:trimegestone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D002784:Cholesterol; D011397:Promegestone; D005996:Nitroglycerin