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Journal of Lipid Research, Vol. 47, 349-355, February 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer

Jonathan Q. Purnell^1,*,, Lisa B. Bland, Mark Garzotto, Dianne Lemmon^**, Emily M. Wersinger^**, Christopher W. Ryan^**, John D. Brunzell and Tomasz M. Beer^**

^* Department of Medicine, Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland, OR 97239
Center for the Study of Weight Regulation, Oregon Health and Science University, Portland, OR 97239
Division of Urology, Portland VA Medical Center, Portland, OR 97239
^** Division of Hematology & Medical Oncology, Portland VA Medical Center, Portland, OR 97239
Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA 98195

Published, JLR Papers in Press, November 20, 2005.

¹ To whom correspondence should be addressed. e-mail: purnellj{at}ohsu.edu

Androgen deprivation therapy (ADT) for prostate cancer is now used in earlier disease stages and as adjuvant treatment. Recognizing and reducing the toxicity of this therapy, including worsened lipid levels and cardiovascular disease (CVD) risks, has become an important clinical concern. Oral estrogen therapy induces hypogonadism and mitigates many side effects of ADT, but has a high thrombosis risk. Transdermal estrogen therapy (TDE) has a lower thrombosis risk than oral estrogen and may improve CVD risk compared with ADT. This prospective pilot study of 18 men with androgen-independent prostate cancer receiving ADT measured effects of TDE on lipid and inflammatory CVD risk factors before and after 8 weeks of TDE (estradiol 0.6 mg/day). During treatment, estradiol levels rose 17-fold; total cholesterol, LDL cholesterol, and apolipoprotein B levels decreased. HDL₂ cholesterol increased, with no changes in triglyceride or VLDL cholesterol levels. Dense LDL cholesterol decreased and LDL buoyancy increased in association with a decrease in HL activity. Highly sensitive C-reactive protein levels and other inflammatory markers did not worsen. Compared with ADT, short-term TDE therapy of prostate cancer improves lipid levels without deterioration of CVD-associated inflammatory markers and may, on longer-term follow-up, improve CVD and mortality rates.

Abbreviations: ADT, androgen deprivation therapy; CVD, cardiovascular disease; DEXA, dual energy X-ray absorptiometry; hs-CRP, high-sensitive C-reactive protein; IL-6, interleukin-6; SHBG, sex hormone binding globulin; TDE, transdermal estrogen therapy; TNF, tumor necrosis factor-

Supplementary key words estradiol • apolipoprotein • inflammation • androgen deprivation therapy

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