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F O R P H Y S I C I A N S – resources
Selective Estrogen Receptor Modulators
Introduction
The menopausal state is characterized by a decrease in ovarian production of estrogens resulting in an increase in the risk of osteoporosis, cardiovascular disease and Alzheimer's disease (1,2,3). The majority of women can now expect to live well beyond the menopausal years increasing the likelihood that these conditions will be the cause of significant morbidity and mortality among this group. It is estimated that a woman's risk of sustaining a hip fracture is between 11% and 18% (4, 5). Furthermore, 36% of women 55 to 64 years old and 55% of women >75 years old are significantly disabled by cardiovascular diseases (6). Furthermore, half of these women will be severely disabled and 1 in 6 will die as a result of the hip fracture (7). Despite a growing body of evidence supporting the use of hormone replacement therapy (HRT) to prevent and treat some of these disorders, controversy regarding an increased risk in breast cancer and uterine cancer have fueled research into other treatment modalities such as selective estrogen receptor modulators (SERM). These compounds bind to and interact with estrogen receptors acting as estrogen agonists in some tissue and as estrogen antagonists in others. Ideally, these compounds would mimic the effect of estrogen on the skeleton, cardiovascular system and central nervous system, while having no estrogenic effect on the breast and reproductive system.
SERMs are a group of structurally diverse compounds with mixed agonist and antagonist activities, which include the triphenylethylenes, such as clomiphene (Serophene, Clomid), tamoxifen (Nolvadex) and toremifene (Fareston) and the benzothiophene derivatives such as raloxifene (Evista). SERMs that reduce postmenopausal bone loss, exert a beneficial effect on serum lipids and cardiovascular function and do not stimulate the endometrium and breast tissue are currently receiving the most attention. The exact mechanism of how SERMs exert tissue-selective effects is unknown, but their mechanism of action is currently under intense investigation as the distribution of estrogen receptors (ER) and their different roles in gene regulation is elucidated.
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