Short-term hormone replacement therapy: reduced plasma levels of soluble adhesion molecules

Background Epidemiological data have suggested that the use of hormone repl acement therapy (HRT) is associated with a decreased risk of cardiovascular disease. Vascular endothelium and adhesion molecules play an important rol e in the initiation and progression of atherosclerosis. Material and methods Prospective, randomized, placebo-controlled 12-week st udy. Sixty healthy, normotensive postmenopausal women received either micro nised oestradiol 2 mg alone (n = 16, E-2 group), or sequentially combined w ith a progestagen; E-2 + P groups trimegestone 0.5 mg (E-2 + T, n = 14) or dydrogesterone 10 mg (E-2 + 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 E-2 or E-2 + 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 t hose treated with dydrogesterone; for sICAM-1 (-15% vs. -2%; P < 0.0001), s VCAM-1 (-15% vs. +3%; P = 0.003) and sTM (-9% vs. -4%; P = 0.11). Plasma le vels of endothelin-1 (ET-1) decreased (by 13%) only in women treated with E -2 + P. In the E-2 group, flow-mediated, endothelium-dependent vasodilatati on increased by 6 percentage points after 12 weeks (P = 0.07 vs, baseline, P = 0.02 vs. E-2 + P, and P = 0.17 vs. placebo). Conclusion Short-term treatment with E-2 or E-2 + trimegestone reduces plas ma levels of sICAM-1, sVCAM-1 and sTM. ET-1 decreased only in the E-2 + P g roups. Different types of progestagens may differentially affect sICAM-1, s VCAM-1 and sTM levels, which may be relevant for the choice of type HRT.