Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women.
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.


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 P< or =0.02 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.
Koh
Kwang Kon
KK
Gachon Medical College, Inchon, South Korea.
Schenke
William H
WH
Waclawiw
Myron A
MA
Csako
Gyorgy
G
Cannon
Richard O
RO
D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use*
D004966:Estrogens, Conjugated (USP); D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D002097:C-Reactive Protein; D019821:Simvastatin