Journal
MATURITAS
Volume 43, Issue 1, Pages 1-10Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/S0378-5122(02)00141-X
Keywords
estradiol; metabolites; carcinogenesis; cancer therapy
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Endogenous estradiol metabolism results in metabolic products that are still capable of exerting various biological, partially estrogen-antagonistic actions. This indicates that the effects of estradiol in carcinogenesis may depend on individual variations of metabolic breakdown of estradiol. The aim of this paper is to review and discuss the available data relating to stimulatory and inhibitory properties of estradiol metabolites on carcinogenesis. Results of main D-ring metabolites and main A-ring metabolites are presented. There are indications that the endogenous production of growth influencing estradiol metabolites may be elevated in neoplasias. Some results in this respect are available for stimulating tumor growth for the D-ring metabolite 16-hydroxyestrone and the A-ring metabolites 4-hydroxyestrone and 4-hydroxyestradiol. Inhibitory effects exist for the A-ring metabolite 2-methoxyestradiol (2-ME). So far, only a few metabolites have been studied closely for their influence on carcinogenesis. There is also a dearth of data on the intracellular metabolism of estradiol in neoplastic tissues: Knowledge of the metabolites may reveal new approaches to diagnosis and treatment of malignant diseases. 2-ME has already shown actions in pharmacological dosages which led already to a first trial to prove its suitability for treating human breast cancer. (C) 2002 Published by Elsevier Science Ireland Ltd.
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