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

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Abstract
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.Material and 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).Conclusion: 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.