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Journal Article
Review
Selective estrogen receptor modulators: a look ahead.
Drugs 1999 May
Selective estrogen receptor modulators (SERMs) are structurally diverse compounds that bind to estrogen receptors (ER) and elicit agonist or antagonist responses depending on the target tissue and hormonal milieu. They are being evaluated primarily for conditions associated with aging, including hormone-responsive cancer, osteoporosis and cardiovascular disease. Several SERMs are marketed or are in clinical development, including triphenylethylenes (tamoxifen and its derivatives: toremifene, droloxifene and idoxifene), chromans (levormeloxifene), benzothiophenes (raloxifene, LY353381) and naphthalenes (CP336,156). Tamoxifen and toremifene, both used to treat advanced breast cancer, also have beneficial effects on bone mineral density and serum lipids in postmenopausal women. Tamoxifen was recently shown to decrease the risk of invasive breast cancer in women at high risk. Unfortunately, both drugs also have stimulatory effects on the endometrium. Raloxifene, used for prevention of postmenopausal osteoporosis and fragility fractures, also has favourable effects on bone mineral density, serum lipids and the incidence of invasive breast cancer in postmenopausal women but does not stimulate the endometrium. Like replacement estrogens, SERMs increase the risk of venous thromboembolism. SERMs offer post-menopausal women many of the advantages of estrogen replacement while mitigating some of the disadvantages, particularly the concern over breast cancer. Newer SERMs, exemplified by raloxifene, also eliminate the concerns over endometrial stimulation that were not addressed by first generation SERMs. The clinical success of SERMs has set the stage for a variety of drug therapies based on selective modulation of nuclear receptor activity.
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