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

Abstract

The goal of this randomized, open-label, crossover clinical trial was to compare the effects of oral and transdermal estrogen therapy in 25 healthy, naturally menopausal women who were taking estrogen-progestin hormone therapy (HT). Following a 6-week period of withdrawal from ongoing HT, participants received oral conjugated equine estrogens (CEEs) in a daily dose of 0.625 mg or 0.05 mg daily of transdermal estradiol (E 2 ) for 12 weeks. Participants received 100 mg daily of oral micronized progesterone continuously during both regimens. Numerous parameters changed significantly during oral CEE therapy when the median percent change from baseline was estimated. They included C-reactive protein (192%), E-selectin (-16%), P-selectin (-15%), intercellular adhesion molecule-1, or ICAM-1 (-5%), and transferrin (5%). Other parameters significantly influenced by oral CEE administration included insulin-like growth factor-I, or IGF-1 (-30.5%), sex hormone-binding globulin, or SHBG (113%), thyroxine-binding globulin (38%), and cortisol-binding globulin (20%). With transdermal E 2 , only 3 parameters changed significantly, and to a lesser degree than with oral CEE: ICAM-1 (-2%), IGF-I (-12.5%), and SHBG (3%). With oral CEE, intra-subject changes in C-reactive protein (CRP) correlated strongly with changes in serum amyloid A but were only weakly associated with changes in SHBG, thyroxine binding globulin, and cortisol-binding globulin. Both regimens were well tolerated and caused no clinically important changes in heart rate, blood pressure, or body weight. These findings suggest that transdermal estrogen therapy (ET)/HT may be preferable to oral ET/HT because it minimizes the hepatic estrogen exposure that increases CRP and levels of coagulation markers and reduces IGF-1.