P-537: Differential effects of transdermal vs. oral estrogen on C-reactive protein in normotensive and hypertensive postmenopausal women

• Published in: American journal of hypertension 2002-04, Vol.15 (S3), p.227A-227A
• Main Authors: Tuncel, M., Wang, Z., Arbique, D., Mehrad, B., Vongpatanasin, W.
• Format: Article
• Language: English
• Subjects: Estrogen; Inflammation; Menopause
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(02)02888-1

We previously demonstrated that estrogen replacement therapy (ERT) decreased sympathetic nerve activity and blood pressure (BP) in postmenopausal women. However, the sympathoinhibitory and BP-lowering effect of estrogen is limited to transdermal, not oral route of administration, because of adverse first-pass hepatic effects of oral estrogen negating beneficial effects of estrogen on neural control of BP. The purpose of this study is to determine if the route of ERT has any influence on serum C-reactive protein (CRP), a marker of inflammation and atherosclerosis produced by hepatocytes. In 16 postmenopausal women (10 normotensive and 6 hypertensive women), we measured serum C-reactive protein before and after eight weeks of transdermal estradiol (200 mcg/day), oral conjugated estrogens (0.625 mg/day), or placebo, using a randomized crossover design. The major new finding was that oral ERT caused a 2-fold increase in CRP concentration (from 1.8 +/− 0.5 to 4.2 +/− 1.6 mg/L, p = 0.01), whereas, in the same women, transdermal ERT and placebo was without effect 1.9+/− 0.5 and 2.5 +/− 1.2, respectively). Because CRP is a critical component in determination of plaque stability and powerful predictor of future cardiovascular events in postmenopausal women, these experimental findings offer a potential explanation for the difficulty in demonstrating cardioprotective effects of estrogen in large clinical trials, which mainly used the oral estrogen. Because proinflammatory effects of oral ERT are not seen with transdermal ERT, the route of administration may be important consideration in optimizing the beneficial effects of ERT on overall cardiovascular health.