TY - JOUR
T1 - Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women
AU - Decensi, Andrea
AU - Omodei, Umberto
AU - Robertson, Chris
AU - Bonanni, Bernardo
AU - Guerrieri-Gonzaga, Aliana
AU - Ramazzotto, Francesca
AU - Johansson, Harriet
AU - Mora, Serena
AU - Sandri, Maria Teresa
AU - Cazzaniga, Massimiliano
AU - Franchi, Massimo
AU - Pecorelli, Sergio
PY - 2002/9/3
Y1 - 2002/9/3
N2 - Background - The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2x2 retinoid-placebo trial. Methods and Results - A total of 189 postmenopausal women were randomized to 50 μg/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 μg/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI -9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI - 14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was -48% (95% CI -85% to -7%, P=0.012), whereas fenretinide was associated with a mean change of -1% (95% CI -34% to 40%, P=0.79) compared with placebo. Conclusions - In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.
AB - Background - The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2x2 retinoid-placebo trial. Methods and Results - A total of 189 postmenopausal women were randomized to 50 μg/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 μg/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI -9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI - 14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was -48% (95% CI -85% to -7%, P=0.012), whereas fenretinide was associated with a mean change of -1% (95% CI -34% to 40%, P=0.79) compared with placebo. Conclusions - In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.
KW - Coronary disease
KW - Hormones
KW - Inflammation
KW - Prevention
KW - Risk factors
UR - http://www.scopus.com/inward/record.url?scp=0037015287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037015287&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.0000028463.74880.EA
DO - 10.1161/01.CIR.0000028463.74880.EA
M3 - Article
C2 - 12208797
AN - SCOPUS:0037015287
VL - 106
SP - 1224
EP - 1228
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 10
ER -