Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study.
BACKGROUND
Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events. In contrast, in a recent clinical trial of women with coronary disease, a subgroup analysis demonstrated increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of hormones on these factors is of interest.


RESULTS
Four inflammation-sensitive factors, C-reactive protein, soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors. Compared with placebo, all 4 active preparations resulted in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin (P=0.0001). There were no effects of treatment on concentrations of von Willebrand factor or factor VIIIc. There were no differences in effects among treatment arms. Relative to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower compared with baseline.


CONCLUSIONS
Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related to adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an anti-inflammatory effect. Because PEPI was not designed to assess clinical endpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.
Cushman
M
M
Departments of Medicine, and Biochemistry, University of Vermont, Burlington, VT 05446, USA. mcushman@salus.uvm.edu
Legault
C
C
Barrett-Connor
E
E
Stefanick
M L
ML
Kessler
C
C
Judd
H L
HL
Sakkinen
P A
PA
Tracy
R P
RP
D000941:Antigens / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000627:therapeutic use; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007249:Inflammation; D008055:Lipids / Q000097:blood; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000276:immunology
D000941:Antigens; D015415:Biomarkers; D001786:Blood Glucose; D019040:E-Selectin; D004966:Estrogens, Conjugated (USP); D008055:Lipids; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D011374:Progesterone; D005169:Factor VIII; D002097:C-Reactive Protein; D017258:Medroxyprogesterone Acetate