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Summary
Kloosterboer HJ  
Die Rolle der Sulfatasehemmung und andere Wirkungen von Tibolon auf die Brust

Journal für Menopause 2003; 10 (Sonderheft 3) (Ausgabe für Österreich): 2-8

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Abb. 1: Tibolon - Metabolismus Abb. 2: Tibolon - Plasmakonzentration Abb. 3: Tibolon -Tamoxifen - DMBA-Modell Abb. 4: Sulfatase - Sulfotransferase Abb. 5: Tibolon - Gewebeselektive Wirkung



Keywords: BrustEstrogenHormonersatztherapieHRTLivielMammakarzinomMenopauseOrganon GesmbHProgestagenSulfatasehemmungTibolon

Hormone treatment with an estrogen plus a progestagen increases the risk of breast cancer. Both hormone activities reside also in tibolone. In order to assess the breast safety of tibolone the compound was evaluated in various preclinical models. In breast cancer cell lines the effects of tibolone were inconclusive, but in various in vivo models it did not stimulate the breast. In the DMBA model tibolone clearly inhibited the growth of breast tumors and when tibolone is given in a prophylactic design far less tumors develop. Ovariectomized monkeys treated for two years with tibolone show no increase in the expression of the proliferation marker Ki67. Several investigations were performed in order to unravel the mode of action of tibolone in breast tissue. The effects of tibolone and its metabolites on the various steroid metabolizing enzymes in breast tissues were therefore investigated. Tibolone or its metabolites did not inhibit the enzyme aromatase, but sulfatase was profoundly inhibited. The sulfated 3 alpha-OH tibolone metabolite showed even irreversible inhibition of the sulfatase enzyme. In addition, it was found that the enzyme 17 beta-hydroxy-steroid dehydrogenase activity was also slightly inhibited and sulfotransferase activity was stimulated at low concentrations. The consequence of the effects of tibolone on these enzymes is that for both the endogenous estrogens and the estrogenic metabolites of tibolone the equilibrium is preferentially at the site of the sulfated forms. Besides this effect on the intracellular hormonal milieu tibolone and its metabolites also influence cellular homeostasis. It inhibits cell proliferation of normal breast epithelial cells and stimulates apoptosis. In this respect, tibolone behaves differently to estrogens. Clinical studies have shown that tibolone users experience less breast tenderness and do not show an increase in mammographic density as found with continuous combined estrogen plus progestagen preparations. The data about tibolone and breast cancer risk are inconclusive and require further investigation.
 
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