Objective - Although oral estrogen replacement therapy (ERT) in postmenopausal women improves endothelial function, it also increases plasma C-reactive protein (CRP) and interleukin- 6 (IL-6) concentration. The proinflammatory effect of oral ERT may explain the increased risk of coronary heart disease (CHD) associated with this treatment. Recent observational studies have demonstrated that a lower dose of oral estrogen reduces the risk for CHD. The purpose of the present study was to investigate the effects of low-dose oral estrogen on vascular inflammatory markers and endothelium-dependent vasodilation in postmenopausal women.
Methods and Results - Postmenopausal women were randomized into 3 groups to receive no treatment ( n = 14) or oral conjugated equine estrogen (CEE) at a dosage of 0.625 mg ( n = 15) or 0.3125 mg ( n = 15) daily for 3 months. CEE at a dosage of 0.625 mg resulted in significant increases in plasma concentrations of CRP from 690.9 +/- 749.5 to 1541.9 +/- 1608.0 ng/mL, serum amyloid A from 6.12 +/- 4.15 to 8.25 +/- 4.40 mug/mL, and IL-6 from 1.45 +/- 0.73 to 2.35 +/- 1.16 pg/mL. In contrast, CEE at a dosage of 0.3125 mg had no effect on these inflammatory markers. Both dosages of estrogen significantly decreased E-selectin concentration, whereas the concentrations of intercellular and vascular cell adhesion molecules remained unchanged. In both CEE groups, flow-mediated vasodilation in the brachial artery was increased significantly, whereas nitroglycerine-induced vasodilation was unaltered.
Conclusions - Oral CEE at a low dose of 0.3125 mg in postmenopausal women eliminated the adverse effects of high-dosage oral CEE on vascular inflammatory markers in addition to preserving the favorable effects of estrogen on cell adhesion molecules and endothelial function.