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Novel agents to modulate oestrogen action.

R C Dardes·V C Jordan
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Abstract

As women enter the menopause, the majority suffers symptoms associated with a dramatic fall in circulating levels of 17 beta-oestradiol and oestrone. As a result, the oestrogen protective effect against coronary artery disease and osteoporosis is lost. To solve these problems, hormone replacement therapy is often used. However, there are a number of side-effects including increased risk from breast and uterine cancer that can limit compliance. New drugs, called selective oestrogen modulators (SERMs), have been developed to mimic oestrogen's effects on the liver, heart and bones but without its harmful effects on the breast and uterus. SERMs are structurally diverse compounds that bind to oestrogen receptors and elicit agonist or antagonist responses depending on the target tissue and hormonal milieu. The drugs are being used, or evaluated, for the prevention of hormone-responsive breast cancer, osteoporosis and cardiovascular disease in postmenopausal women. Tamoxifen is the endocrine treatment of choice for breast cancer, but it also has beneficial effects on bone density and serum lipids in postmenopausal women. Recently, tamoxifen was shown to decrease the risk of invasive breast cancer in women at high risk. However, tamoxifen has some stimulatory effects on the endometrium. Raloxifene is used to prevent osteoporosis and fractures. Raloxifene also lowers circulating cholesterol and the incidence of invasive breast cancer in postmenopausal women but does not stimulate the endometrium. The SERMs have evolved from mere laboratory curiosities into drugs that hold promise for preventing several major diseases associated with ageing in women.

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Breast NeoplasmsCoronary DiseaseEstrogen Replacement TherapyFemaleHumansMiddle AgedOsteoporosis, PostmenopausalPostmenopauseRaloxifene HydrochlorideReceptors, EstrogenSelective Estrogen Receptor ModulatorsTamoxifenJournal ArticleReview

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BibTeXRIS

R C Dardes, V C Jordan. 2000. Novel agents to modulate oestrogen action.. https://doi.org/10.1258/0007142001903355

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