Effect of hormone replacement therapy on nitric oxide bioactivity and monocyte chemoattractant protein-1 levels.
BACKGROUND
Vascular inflammation plays an important role in the pathogenesis of atherosclerosis. We investigated the effect of hormone replacement therapy (HRT) on vasomotor function and monocyte chemoattractant protein (MCP)-1 levels, an important serological marker of inflammation.


METHODS
We administered micronized progesterone (MP) 200 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and remaining 5 days off cyclically during 2 months to 20 healthy postmenopausal women (PMW). We measured NO bioactivity and plasma levels of MCP-1 before and after HRT in 20 PMW. And we measured plasma levels of MCP-1 in each 20 subjects of premenopausal women, men <50, and men >50 years, respectively.


RESULTS
MP combined with CEE significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P<0.001). PMW receiving HRT had lower levels of MCP-1 than those not receiving HRT (121+/-38 versus 146+/-44 pg/ml, P<0.001). In all comparisons, subjects with high estrogen status had significantly lower MCP-1 levels than subjects with low estrogen status (P<0.001 by ANOVA). Premenopausal women had lower levels of MCP-1 than men of a similar age (106+/-14 versus 164+/-40 pg/ml, P<0.001). PMW not receiving HRT had similar levels of MCP-1 compared with men of a similar age (146+/-44 versus 143+/-29 pg/ml, P=0.816). Premenopausal women had markedly lower levels of MCP-1 than PMW not receiving HRT (106+/-14 versus 146+/-44 pg/ml, P=0.001). PMW receiving HRT had similar levels of MCP-1 compared with premenopausal women (121+/-38 versus 106+/-14 pg/ml, P=0.323).


CONCLUSIONS
These findings might provide at least a partial explanation for the protection against cardiovascular disease experienced by premenopausal women, and the loss of that protection following menopause.
Koh
K K
KK
Cardiology, Gachon Medical School, Inchon, South Korea 405-760. kwangk@ghil.com
Son
J W
JW
Ahn
J Y
JY
Lee
S K
SK
Hwang
H Y
HY
Kim
D S
DS
Jin
D K
DK
Ahn
T H
TH
Shin
E K
EK
D000367:Age Factors; D000704:Analysis of Variance; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000378:metabolism*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D017698:Postmenopause / Q000378:metabolism; D017697:Premenopause / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D012737:Sex Factors; D014463:Ultrasonography
D018932:Chemokine CCL2; D004966:Estrogens, Conjugated (USP); D009569:Nitric Oxide; D011374:Progesterone