Associations between markers of inflammation and physiological and pharmacological levels of circulating sex hormones in postmenopausal women.
OBJECTIVE
Hormone therapy has been shown to reduce markers of vascular inflammation in . C-reactive protein (CRP), a marker of generalized inflammation, is raised by oral estradiol therapy (ET). It is not known how sex hormone concentrations relate to the markers of inflammation in postmenopausal women taking or not taking hormone therapy.


METHODS
This observational study includes postmenopausal women participating in the Estrogen in the Prevention of Atherosclerosis Trial. Multiple measures of serum sex hormone and sex hormone-binding globulin(SHBG) levels from 107 postmenopausal women taking oral ET and 109 taking placebo for 2 years were correlated with markers of inflammation over the same time period using generalized estimating equations.


RESULTS
Levels of soluble intercellular adhesion molecule-1 were significantly inversely associated with estrone(P = 0.05), total and free estradiol (P = 0.008 and 0.02, respectively), and SHBG (P = 0.03) only among oral ET users. Serum homocysteine levels were also inversely associated with estrone (P = 0.001) and total and free estradiol (P = 0.0006 and 0.0009, respectively) in ET-treated women only. No such associations were observed among women taking placebo. CRP was positively associated with estrogens and SHBG among women taking oral ET but inversely associated with SHBG among the placebo group.


CONCLUSIONS
The inverse associations of estrogens with soluble intercellular adhesion molecule-1 and homocysteine support an anti-inflammatory property of estrogen, which was observed only at pharmacological levels in postmenopausal women. The positive associations between estrogens and CRP in the ET-treated women can be explained by the first-pass hepatic effect rather than a proinflammatory response.
Karim
Roksana
R
Department of Pediatrics and Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA. rkarim@usc.edu
Stanczyk
Frank Z
FZ
Hodis
Howard N
HN
Cushman
Mary
M
Lobo
Roger A
RA
Hwang
Juliana
J
Mack
Wendy J
WJ
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage; D004970:Estrone / Q000097:blood*; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D013739:Testosterone / Q000097:blood
D015415:Biomarkers; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D002097:C-Reactive Protein