Abstract
Objective
The objective of this study was to determine whether oral conjugated equine estrogen
(CEE) alone or with one of the three progestin regimens causes changes in biomarkers
predictive of adverse cardiovascular events: C-reactive protein (CRP), interleukin-6
(IL-6), intercellular adhesion molecule (ICAM) and matrix metalloproteinase-9 (MMP-9).
Methods and results
The analysis included 271 postmenopausal women from the postmenopausal estrogen progestin
intervention (PEPI) trial. Plasma levels of biomarkers were measured on frozen samples
obtained at baseline, 1- and 3-year follow-up visits. Multivariable linear mixed effects
models were used to estimate changes in CRP, IL-6, ICAM and MMP-9 levels from baseline
to follow-up visits by treatment groups. Women assigned to CEE only or CEE plus a
progestin had 121 and 150% 1-year increase in CRP levels, respectively. In contrast,
these treatments caused no significant change in IL-6 levels. Women assigned to CEE
with or without a progestin had a 6–8% decline in ICAM and a 26–33% decline in MMP-9.
Conclusions
The linkage between CEE alone or with a progestin and increased cardiovascular events
may be associated with a rise in CRP level, but not through the mechanisms of IL-6-mediated
inflammation, endothelial dysfunction or increased MMP activity.
Keywords
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Article info
Publication history
Published online: July 18, 2005
Accepted:
June 8,
2005
Received in revised form:
May 31,
2005
Received:
April 1,
2005
Identification
Copyright
© 2005 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
