A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women.
OBJECTIVE
Our objective was to compare the effects of oral vs. transdermal estrogen therapy on C-reactive protein (CRP), IL-6, E- and P-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1, serum amyloid A, transferrin, prealbumin, IGF-I, SHBG, thyroxine-binding globulin (TBG), and cortisol-binding globulin (CBG) in naturally menopausal women.


METHODS
This was a randomized, open-label crossover clinical trial. A 6-wk withdrawal from prior hormone therapy (baseline) was followed in randomized order by 12-wk oral conjugated equine estrogens (CEEs) (0.625 mg/d) and 12-wk transdermal estradiol (E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both regimens.


RESULTS
A total of 27 women enrolled, and 25 completed both treatment periods. Nine parameters changed significantly during oral CEE (median percent change from baseline; P value): CRP (192%; P <0.001); E-selectin (-16.3%; P = 0.003); P-selectin (-15.3%; P = 0.012); ICAM-1 (-5%; P = 0.015); transferrin (5.3%; P = 0.024); IGF-I (-30.5%; P < 0.001); SHBG (113%; P < 0.001); TBG (38%; P < 0.001); and CBG (20%; P < 0.001). With transdermal E2, only three parameters changed significantly and to a lesser degree: ICAM-1 (-2.1%; P = 0.04); IGF-I (-12.5%; P < 0.001); and SHBG (2.6%; P = 0.042). During oral CEE the intrasubject changes in CRP correlated strongly with the changes in serum amyloid A (r = 0.805; P < 0.001), and were only weakly associated with the changes in SHBG (r = 0.248; nonsignificant), TBG (0.430; P = 0.031), and CBG (r = 0.072; nonsignificant). The log-log relationship between CRP and IL-6 observed at baseline showed a parallel shift during oral CEE, suggesting an amplified hepatic response or a greater sensitivity to IL-6 stimulation.


CONCLUSIONS
Compared with oral CEE, transdermal E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters.
Shifren
Jan L
JL
Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, 670 Albany Street, Boston, MA 02118, USA. jshifren@partners.org
Rifai
Nader
N
Desindes
Sophie
S
McIlwain
Marilyn
M
Doros
Gheorghe
G
Mazer
Norman A
NA
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis*; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008593:Menopause / Q000097:blood*; D008875:Middle Aged; D011228:Prealbumin / Q000032:analysis; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D014168:Transferrin / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D004966:Estrogens, Conjugated (USP); D015850:Interleukin-6; D011228:Prealbumin; D012738:Sex Hormone-Binding Globulin; D014168:Transferrin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol; D002097:C-Reactive Protein