Tamoxifen: oestrogen or anti-oestrogen in bone?

摘要

The evidence to date strongly suggests that tamoxifen has oestrogenic effects on bone and provides reassurance for women on long-term therapy who are concerned about osteoporosis. Overall, the increases in bone density reported in prospective studies of tamoxifen-treated women have been less than those observed in healthy postmenopausal women receiving hormone replacement therapy, suggesting that tamoxifen may act in bone as a partial, rather than complete, oestrogen agonist. However, many of these studies have been small and pooriy controlled, and firm conclusions about the magnitude of tamoxifen-induced effects on bone must await large, long-term prospective studies. The recently initiated trial of tamoxifen prophylaxis for breast cancer in the UK provides an ideal opportunity for such a study. The apparent bone-preserving properties of tamoxifen raise the possibility that this drug might be used as an alternative to oestrogen in the prophylaxis of osteoporosis. However, the failure of tamoxifen to alleviate menopausal symptoms and its oestrogenic effects on the endometrium and probably also the liver are significant disadvantages and other, non-hormonal options, for example bisphosphonates, exist for women who have breast cancer or are at high risk from this disease. Nevertheless, tamoxifen has provided an important example of how a single agent may have both oestrogenic and anti-oestrogenic effects within a single species, and has stimulated research into the development of other, more selective agonists which may retain beneficial oestrogenic actions whilst possessing neutral or anti-oestrogenic effects on the breast, liver and endometrium.