[Effect of selective estrogen receptor modulators on estrogen-sensitive tissues].
Selective estrogen receptor modulators (SERMs) act exclusively through estrogen receptors and possess tissue-specific agonistic or antagonistic properties. The effects of all referred SERMs in bone and cardiovascular system are estrogenic, namely they inhibit postmenopausal bone loss and favorably influence plasma lipoproteins and some coagulation factors. The aim of this paper is to review the effects of SERMs on estrogen-dependent breast tissues and on the endometrium. There are two types of SERMs in clinical use, based on their chemical structure: the triphenylethylenes and the benzothiophenes. The prototype of the SERMs with triphenylethylene structure is tamoxifen. Tamoxifen, like all other SERMs, is an estrogen antagonist in the breast and is widely used for adjuvant treatment of breast cancer. A recent study suggests that tamoxifen also may prevent breast cancer in patients at risk. Because of the partial estrogenic activity of tamoxifen in the endometrium, its clinical use is associated with uterine hypertrophy and an increased risk of endometrial cancer. Other triphenylethylene SERMs, droloxifene, toremifene, and idoxifene, also show efficacy in the treatment of breast cancer, in a manner similar to tamoxifen. A better toxicology profile and a decreased endometrial estrogen agonism may be advantages of the new triphenylethylene SERMs. Raloxifene is a SERM with a chemical structure different from triphenylethylenes. Raloxifene, a benzothiophene, possesses an estrogen-antagonistic effect in the breast similar to triphenylethylenes. Clinical studies on postmenopausal osteoporotic women on raloxifene as compared with placebo show a significant decrease in the rate of newly diagnosed breast cancers. In clinical studies, in contrast to tamoxifen, no stimulatory effect in the endometrium could be observed with raloxifene.
Jirecek
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Abteilungen für Geburtshilfe und Gynäkologie, Universitätsklinik für Frauenheilkunde, Wien, Osterreich. Stefan.Jirecek@akh-wien.ac.at
Pavo
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Huber
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JC
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001940:Breast / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000187:drug effects*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators