SELECTIVE ESTROGEN-RECEPTOR MODULATORS (SERMS)

Naturally occurring estrogens, such as 17 beta-estradiol and estrone, have traditionally been thought to play a central role in the developm ent and maintenance of the female reproductive system and secondary se xual characteristics. In recent years, their beneficial effects on the skeleton, the cardiovascular system, and the central nervous system, as well as the cancer risks associated with long term exposure have al so been recognized. The widespread use of ''antiestrogens'' such as ta moxifen for the prevention and treatment of breast cancer has revealed that such compounds, while functioning as estrogen antagonists in mam mary tissue, actually mimic the effects of estrogen in other tissues. The search for more selective agents has led to the development of ral oxifene, a Selective Estrogen Receptor Modulator, which functions as a n estrogen antagonist in the breast and uterus and as an estrogen agon ist in the skeleton and cardiovascular system. Recent progress in the development of SERMs is the subject of this review, with an emphasis o n structure activity relationships and on their effects in non-traditi onal target tissues.