Different effects of oral conjugated estrogen and transdermal estradiol on arterial stiffness and vascular inflammatory markers in postmenopausal women

Aims We compared the effects of oral conjugated equine estrogen (CEE) therapy and transdermal estradiol therapy on pulse wave velocity (PWV) and circulating levels of vascular inflammatory markers in postmenopausal women and we also explored the interrelationship between the change in PWV and the changes in vascular inflammatory markers. Methods and results In a randomized 12-month trial, 28 postmenopausal women received a continuous oral CEE plus cyclic medroxyprogesterone acetate (MPA), 28 received a continuous transdermal estradiol patch plus cyclic MPA, and 27 did not receive either therapy. In each subject, we measured the brachial-ankle PWV (baPWV) using an automated device, the blood pressure, and the circulating levels of vascular inflammatory markers (C-reactive protein [CRP], cell adhesion molecules [CAMs], monocyte chemoattractant protein-1 [MCP-1], and matrix metalloproteinase [MMP-9]) before and 12 months after the start of the study. Oral CEE therapy did not change the baPWV but significantly increased the CRP and MMP-9 levels (P < 0.05, each) and significantly decreased the CAMs and MCP-1 levels (P < 0.05, each). Transdermal estradiol therapy significantly decreased the baPWV, and the CAMs and MCP-1 levels (P < 0.05, each) but had no effect on the CRP or MMP-9 levels. No significant changes were seen in the control group. The blood pressures of the subjects remained unchanged. In the transdermal estradiol group, the change in baPWV was not significantly correlated with the changes in vascular inflammatory markers. Conclusion Transdermal estradiol, but not oral CEE therapy, may have antiatherosclerotic effects by improving arterial stiffness. The reduction in baPWV may contribute to the direct effect of estrogen, but not to the decrease in estrogen-induced vascular inflammatory markers.