Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women.
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.


RESULTS
A total of 189 postmenopausal women were randomized to 50 microg/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 microg/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.
Division of Chemoprevention, European Institute of Oncology, Milan, Italy. andrea.decensi@ieo.it
Andrea
A
Decensi
Umberto
U
Omodei
Chris
C
Robertson
Bernardo
B
Bonanni
Aliana
A
Guerrieri-Gonzaga
Francesca
F
Ramazzotto
Harriet
H
Johansson
Serena
S
Mora
Maria Teresa
MT
Sandri
Massimiliano
M
Cazzaniga
Massimo
M
Franchi
Sergio
S
Pecorelli
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000209:etiology / Q000517:prevention & control; D002097:C-Reactive Protein / Q000032:analysis*; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control; D020405:Dermis; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D017698:Postmenopause; D012307:Risk Factors
D000970:Antineoplastic Agents; D015415:Biomarkers; D004966:Estrogens, Conjugated (USP); D017313:Fenretinide; D004958:Estradiol; D002097:C-Reactive Protein