Effects of hormone therapy on soluble cell adhesion molecules in postmenopausal women with coronary artery disease

Although observational studies showed an apparent lower ischemic coronary disease risk in postmenopausal women receiving hormone therapy (HT), randomized clinical trials in postmenopausal women showed an increase in ischemic cardiovascular events. Soluble cell adhesion molecules have been associated with cardiovascular risk factors and events. HT reduces circulating levels of soluble cell adhesion molecules in healthy postmenopausal women, but its effects in postmenopausal women with coronary artery disease are less clear. We assessed the effect of HT on soluble cell adhesion molecules in the Estrogen Replacement and Atherosclerosis trial.

The Estrogen Replacement and Atherosclerosis trial was a double-blind, placebo-controlled study that randomized 309 postmenopausal women (mean age, 65.8 y) to daily unopposed estrogen (conjugated estrogens 0.625 mg), estrogen plus 2.5 mg of medroxyprogesterone acetate, or placebo, with a mean follow-up period of 3.2 years. Soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin were measured in serum obtained from participants at baseline and after 12 months of follow-up.

Of the 265 women with complete data, 87 women were assigned to unopposed estrogen, 88 women to estrogen plus medroxyprogesterone acetate, and 90 women to placebo. Compared with placebo, 12 months of HT (n = 175) was associated with reductions in soluble intercellular adhesion molecule-1 (25.6 +/- 4.7 vs 10.6 +/- 6.4 ng/mL, P = 0.06), soluble vascular cell adhesion molecule-1 (80.2+/- 10.6 vs 28.8 +/- 14.7 ng/mL, P = 0.005), and E-selectin (8.8 +/- 0.9 vs -1.1 +/- 1.2 ng/mL, P < 0.001).

Twelve months of HT in postmenopausal women with established coronary artery disease was associated with reductions in serum markers of endothelial cell activation/injury such as soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin.