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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

Vincent Obstetrics and Gynecology Service (J.L.S.), Massachusetts General Hospital and Department of Pathology (N.R.), Children’s Hospital Medical Center, Harvard Medical School, Boston, Massachusetts 02115; Obstetrics and Gynecology (S.D.), University of Sherbrooke, Sherbrooke, Quebec, Canada J1K 2R1; Clinical Affairs (M.M.), Watson Laboratories, Inc., Morristown, New Jersey 07960; and Department of Biostatistics (G.D.), Boston University School of Public Health and Section of Endocrinology, Diabetes and Nutrition (N.A.M.), Boston University School of Medicine, Boston, Massachusetts 02118

Address all correspondence to: Norman A. Mazer, M.D., Ph.D., Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, Massachusetts 02118. E-mail: nmazer{at}bu.edu.

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.

Design: 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.

Conclusion: Compared with oral CEE, transdermal E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters.