British Medical Bulletin 56:773-786 (2000)
© 2000 The British Council
research-article |
Novel agents to modulate oestrogen action
*Department of Gynaecology, Federal University of Säo Paulo Brazil (UNIFESP)
Department of Molecular Pharmacology & Biological Chemistry, Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School Chicago, Illinois, USA
Correspondence to Dr V Craig Jordan, Director, Lynn Sage Breast Cancer Research Program, Robert H Lurie Comprehensive Cancer Center, Olson Pavilion 8258, 303 E Chicago Avenue, Chicago, IL 60611-3008, USA
Abstract
As women enter the menopause, the majority suffers symptoms associated with a dramatic fall in circulating levels of 17ß-oestradiol and oestrone. As a result, the iestrogen 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 lilmit 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 waomen 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.