The effects of hormone therapy on the markers of inflammation and endothelial function and plasma matrix metalloproteinase-9 level in postmenopausal women: the postmenopausal estrogen progestin intervention (PEPI) trial.
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).


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.
Hu
Peifeng
P
Multicampus Program in Geriatric Medicine and Gerontology, UCLA School of Medicine, 10945 Le Conte Avenue, Suite 2339, Los Angeles, CA 90095-1687, USA. phu@mednet.ucla.edu
Greendale
Gail A
GA
Palla
Shana L
SL
Reboussin
Beth A
BA
Herrington
David M
DM
Barrett-Connor
Elizabeth
E
Reuben
David B
DB
D002097:C-Reactive Protein / Q000032:analysis; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000502:physiology*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood* / Q000502:physiology; D011374:Progesterone / Q000008:administration & dosage*
D004966:Estrogens, Conjugated (USP); D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; D011374:Progesterone; D002097:C-Reactive Protein; D017258:Medroxyprogesterone Acetate; D020780:Matrix Metalloproteinase 9