Published Online
on August 19, 2002

A more recent version of this article appeared on September 3, 2002

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Submitted on April 25, 2002
Revised on June 7, 2002
Accepted on June 17, 2002

Effect of Transdermal Estradiol and Oral Conjugated Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women

Andrea Decensi MD^*, Umberto Omodei MD, Chris Robertson PhD, Bernardo Bonanni MD, Aliana Guerrieri-Gonzaga MSc, Francesca Ramazzotto MD, Harriet Johansson MSc, Serena Mora MSc, Maria Teresa Sandri MD, Massimiliano Cazzaniga MD, Massimo Franchi MD, and Sergio Pecorelli MD

From the Divisions of Chemoprevention (A.D., B.B., A.G.-G., S.M., M.C.), Epidemiology and Biostatistics (C.R.), and Laboratory Medicine (H.J., M.T.S.), European Institute of Oncology, Milan, Italy; the Division of Obstetrics and Gynecology (U.O., F.R., S.P.), University of Brescia, Brescia, Italy; and the Division of Obstetrics and Gynecology (M.F.), University of Varese, Varese, Italy.

^* To whom correspondence should be addressed. E-mail: andrea.decensi{at}ieo.it.

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.

Key words: hormones • inflammation • coronary disease • prevention • risk factors

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