Objective: To compare the effects of oral vs. transdermal estrogen therapy on C-reactive protein (CRP), IL-6, E- and P-selectin, ICAM-1 and VCAM-1, Serum Amyloid A (SAA), Transferrin, Prealbumin, IGF-1, SHBG, TBG and CBG in naturally menopausal women.

Design: Randomized, open-label crossover clinical trial. A 6-week withdrawal from prior hormone therapy (baseline) was followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/day) and 12 weeks of transdermal estradiol (E2) (0.05 mg/day), with oral micronized progesterone (100 mg/day) given continuously during both regimens.

Results: 27 women enrolled and 25 completed both treatment periods. Nine parameters changed significantly during oral CEE (median percentage 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%; 0.024), IGF-1 (-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-1 (-12.5%; P<0.001) and SHBG (2.6%; P=0.042). During oral CEE the intra-subject changes in CRP correlated strongly with the changes in SAA (r=0.805; P<0.001) and were only weakly associated with the changes in SHBG (r=0.248; NS), TBG (0.430; P=0.031) and CBG (r=0.072; NS). 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 to oral CEE, transdermal E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters.