Hormone replacement therapy

Oestrogen deficiency at the menopause leads to bone loss primarily as a result of increased bone turnover and an increase in the activity of osteoclasts. Hormone replacement therapy (HRT) reverses these changes, preventing menopausal bone loss and reducing fracture risk at the spine, hip, and wrist, although the magnitude of this reduction has not been accurately established. The optimal duration of therapy for the prevention of osteoporosis is uncertain but there is increasing evidence that life-long treatment after the menopause may be required to maintain maximum protection against fracture. The extraskeletal effects of long-term oestrogen therapy include protection against cardiovascular disease and a possible increase in the risk of breast cancer; the persistence of these effects after therapy is withdrawn is uncertain although there is some evidence that the increase in risk of breast cancer is seen only in current users. Furthermore, there is increasing evidence that the use of progestogens in combined formulations does not substantially alter either the cardiovascular benefits or the increased risk of breast cancer, although further studies are needed in this area. The emergence of 'no-bleed' preparations in recent years has increased the acceptability of HRT for some women, particularly those in older age groups. Finally, the development of tissue-selective oestrogen agonists is an exciting advance which may enable life-long therapy after the menopause to protect against cardiovascular and bone disease in the absence of significant side-effects.