Selective estrogen receptor modulators (SERMs) are compounds that can act as either estrogen receptor agonists or antagonists depending on the type of tissue. The first clinically useful SERM, tamoxifen, is a very effective agent for the treatment of metastatic breast cancer or when used in the adjuvant setting, but an increased risk of endometrial cancer has been associated with its use due to the partial estrogen agonist effects of tamoxifen on the uterine endometrium. Thus, there has been an intense search for new tamoxifen-like compounds that are devoid of its side effects while having the beneficial effects of estrogen on bone and the cardiovascular system. The results of the Women’s Health Initiative study of hormone replacement therapy (HRT) in postmen- opausal women have made new SERMs even more attractive for alleviation of urogenital atrophy, breast cancer prevention, treatment and prevention of osteoporosis, and possibly for cardiovascular benefits. Of the currently approved SERMs, raloxifene is currently being evaluated for use in breast cancer prevention and for its cardiovascular benefits, while toremifene is in phase II/III clinical trials for use in the prevention of prostate cancer. There are several inves- tigational SERMs currently in development, including ospemifene, lasofoxifene, arzoxifene, and bazedoxifene. Included in this review is an overview of the currently approved SERMs and a discussion of eleven investigational SERMs currently in development.
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