Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy.
OBJECTIVE
The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy.


METHODS
We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy.


RESULTS
all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy.


CONCLUSIONS
Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.
Vitale
Cristiana
C
Cardiovascular Research Unit Department of Medical Sciences, Fondazione San Raffaele IRCCS-Roma, Tosinvest Sanita, Roma, Italy.
Cornoldi
Alessandra
A
Gebara
Otavio
O
Silvestri
Antonello
A
Wajngarten
Mauricio
M
Cerquetani
Elena
E
Fini
Massimo
M
Ramires
José Antonio F
JA
Rosano
Giuseppe M C
GM
D000367:Age Factors; D000726:Androgen Antagonists / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging; D002097:C-Reactive Protein / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000097:blood*; D003271:Contraceptive Agents, Female / Q000627:therapeutic use; D017373:Cyproterone Acetate / Q000627:therapeutic use; D004394:Dydrogesterone / Q000627:therapeutic use; D004958:Estradiol / Q000627:therapeutic use; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D004967:Estrogens / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D009640:Norethindrone / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000627:therapeutic use; D017698:Postmenopause; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D018180:Thrombomodulin / Q000097:blood*; D014463:Ultrasonography
D000726:Androgen Antagonists; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003271:Contraceptive Agents, Female; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D015850:Interleukin-6; D009652:Norpregnenes; D018180:Thrombomodulin; D020849:Raloxifene Hydrochloride; D017373:Cyproterone Acetate; D004958:Estradiol; D002097:C-Reactive Protein; D004394:Dydrogesterone; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; C027385:tibolone; D009640:Norethindrone