Effect of selective estrogen receptor modulators on estrogen-sensitive tissues

Selective estrogen receptor modulators (SERMs) act exclusively through estr ogen receptors and possess tissue-specific agonistic or antagonistic proper ties. The effects of all referred SERMs in bone and cardiovascular system a re estrogenic, namely they inhibit postmenopausal bone loss and favorably i nfluence plasma lipoproteins a nd some coagulation factors. The aim of this paper is to review the effects of SERMs on estrogen-dependent breast tissu es and on the endometrium. There are two types of SERMs in clinical use, ba sed on their chemical structure: the triphenylethylenes and the benzothioph enes. The prototype of the SERMs with triphenylethylene structure is tamoxi fen. Tamoxifen, like all other SERMs, is an estrogen antagonist in the brea st and is widely used for adjuvant treatment of breast cancer. A recent stu dy suggests that tamoxifen also may prevent breast cancer in patients at ri sk. Because of the partial estrogenic activity of tamoxifen in the endometr ium, its clinical use is associated with uterine hypertrophy and an increas ed risk of endometrial cancer. Other triphenylethylene SERMs, droloxifene, toremifene, and idoxifene, also show efficacy in the treatment of breast ca ncer, in a manner similar to tamoxifen. A better toxicology profile and a d ecreased endometrial estrogen agonism may be advantages of the new tripheny lethylene SERMs. Raloxifene is a SERM with a chemical structure different f rom 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 effe ct in the endometrium could be observed with raloxifene. Copyright (C) 1999 S. Karger AG, Basel.