Novel agents to modulate oestrogen action

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 disea se and osteoporosis is lost. To solve these problems, hormone replacement t herapy is often used. However, there are a number of side-effects including increased risk from breast and uterine cancer that can limit compliance. N ew drugs, called selective oestrogen modulators (SERMs), have been develope d to mimic oestrogen's effects on the liver, heart and bones but without it s 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 ar e being used, or evaluated, for the prevention of hormone-responsive breast cancer, osteoporosis and cardiovascular disease in postmenopausal women. T amoxifen is the endocrine treatment of choice for breast cancer, but it als o has beneficial effects on bone density and serum lipids in postmenopausal women. Recently, tamoxifen was shown to decrease the risk of invasive brea st cancer in women at high risk. However, tamoxifen has some stimulatory ef fects on the endometrium. Raloxifene is used to prevent osteoporosis and fr actures. Raloxifene also lowers circulating cholesterol and the incidence o f 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 wi th ageing in women.