Association of Circulating Cellular Adhesion Molecules with Menopausal Status and Hormone Replacement Therapy: Time-Dependent Change in Transdermal, but not Oral Estrogen Users

Abstract

The incidence of coronary heart disease is lower in premenopausal than in postmenopausal women, and estrogen use may be cardioprotective among postmenopausal women. Cellular adhesion molecules (CAM) are involved in the early stage of atherosclerosis, and short-term administration of oral estrogen decreased plasma concentrations of their soluble forms in postmenopausal women. However, data evaluating transdermal estrogen are sparse and long-term effect of hormone replacement therapy (HRT) on CAM is unknown. Therefore, we have investigated the association of circulating CAM (cCAM) with menopausal status and long-term HRT. Plasma levels of intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), P-selectin, E-selectin, C-reactive protein (CRP), and fibrinogen were measured in 74 premenopausal women, 60 postmenopausal women not using HRT, 30 postmenopausal women using opposed oral estrogen therapy, and 30 postmenopausal women using opposed transdermal estrogen therapy. All women were apparently healthy and aged between 45 and 54 years. Duration of HRT ranged from 3 to 96 months. Postmenopausal women not receiving HRT had 24% higher mean levels of cICAM-1 than premenopausal women (318 vs. 255 ng/ml, P<.001). In postmenopausal women, users of oral estrogen had 16% lower, and users of transdermal estrogen had 17% lower mean levels of cICAM-1 than non-users (268 and 264 vs. 318 ng/ml, P=.001 for both comparisons). Furthermore, in users of transdermal route, the lowering effect of estrogen on cICAM-1 was dependent on treatment duration, while no time-dependent effect was seen in oral estrogen users. Users of transdermal estrogen had lower cVCAM-1 and P-selectin levels than postmenopausal non-users (327 vs. 364 ng/ml ( P=.05) and 18 vs. 23 ng/ml ( P=.05). There was no difference in CRP and E-selectin levels between the groups. Adjustment for age and body mass index (BMI) made no substantial change in the results. These data suggest that oral and transdermal estrogen may play a long-term cardioprotective role through favourable changes in endothelial function.