Published Online
on March 11, 2002

A more recent version of this article appeared on April 2, 2002

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Submitted on December 17, 2001
Revised on February 4, 2002
Accepted on February 5, 2002

Statin Attenuates Increase in C-Reactive Protein During Estrogen Replacement Therapy in Postmenopausal Women

Kwang Kon Koh MD, PhD, William H. Schenke BA, Myron A. Waclawiw PhD, Gyorgy Csako MD, and Richard O. Cannon III MD^*

From the Gachon Medical College, Inchon, South Korea (K.K.K.); and the Cardiovascular Branch (W.H.S., R.O.C.) and Office of Biostatistics Research (M.A.W.), National Heart, Lung, and Blood Institute, and the Department of Laboratory Medicine (G.C.), Clinical Center, National Institutes of Health, Bethesda, Md.

^* To whom correspondence should be addressed. E-mail: cannonr{at}nih.gov.

Background—HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular risk, mechanisms of which may include diminished arterial inflammation, as suggested by reduction in levels of C-reactive protein (CRP). Because oral estrogens increase CRP in postmenopausal women, with potential inflammatory and thrombotic consequences that could compromise any benefit to cardiovascular risk, we determined whether the coadministration of a statin might modify the estrogenic effect on CRP.

Methods and Results—In a double-blind, 3-period crossover study, 28 postmenopausal women (average LDL cholesterol 163±36 mg/dL) were randomly assigned to daily conjugated equine estrogens (CEEs) 0.625 mg, simvastatin 10 mg, or their combination for 6 weeks, with each treatment period separated by 6 weeks. CEEs increased median CRP levels from 0.27 to 0.46 mg/dL, simvastatin decreased CRP from 0.29 to 0.28 mg/dL, and the therapies combined increased CRP from 0.28 to 0.36 mg/dL (all P0.02 versus respective baseline values). Post hoc testing showed that the 29% increase in CRP on the combination of CEEs with simvastatin was significantly less than the 70% increase in CRP on CEEs alone (P<0.05). The effect of combination therapy on CRP levels did not correlate with baseline CRP or with baseline or treatment-induced changes in levels of interleukin-6, lipoproteins, or flow-mediated dilation of the brachial artery as a measure of nitric oxide bioactivity.

Conclusions—The combination of statin with estrogen may attenuate the potential harmful effects of estrogen therapy in postmenopausal women and maximize any benefit to cardiovascular risk.

Key words: hormones • women • inflammation • endothelium • hypercholesterolemia

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