Selective estrogen receptor modulators (SERMs)

TLDR

Estrogens regulate reproductive and secondary sexual traits and also benefit bone, heart, and brain, but long‑term exposure carries cancer risks; antiestrogens like tamoxifen act as antagonists in breast yet mimic estrogen elsewhere, prompting development of selective modulators such as raloxifene that act as antagonists in breast/uterus and agonists in bone and cardiovascular tissues. This review surveys recent advances in SERMs, focusing on structure‑activity relationships and their actions in non‑traditional target tissues.

Abstract

Naturally occurring estrogens, such as 17 beta-estradiol and estrone, have traditionally been thought to play a central role in the development and maintenance of the female reproductive system and secondary sexual 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 also been recognized. The widespread use of "antiestrogens" such as tamoxifen for the prevention and treatment of breast cancer has revealed that such compounds, while functioning as estrogen antagonists in mammary tissue, actually mimic the effects of estrogen in other tissues. The search for more selective agents has led to the development of raloxifene, a Selective Estrogen Receptor Modulator, which functions as an estrogen antagonist in the breast and uterus and as an estrogen agonist in the skeleton and cardiovascular system. Recent progress in the development of SERMs is the subject of this review, with an emphasis on structure activity relationships and on their effects in non-traditional target tissues.