Role of oestrogen in the treatment and prevention of Alzheimer's disease.
Alzheimer's disease (AD), the most common primary dementing disorder, results in devastating clinical and socio-economic consequences, and is a leading cause of death among the elderly. Despite recent advances in the neurobiology of AD, identification of effective treatment strategies has remained frustratingly elusive. Administration of currently available cholinergic drugs improves symptoms in some patients with AD, but may be associated with efficacy-limiting adverse effects. Moreover, it is not yet known whether cholinergic drugs have the potential to alter the progression of AD pathology. In contrast, cumulative evidence from basic neuroscience and clinical research demonstrates that oestrogen has significant neuromodulatory and neuroprotective properties. Furthermore, preliminary evidence from clinical studies indicates that oestrogen replacement therapy can significantly enhance cognitive function in postmenopausal women with AD, and reduce the risk for developing the disease. However, long-term administration of oestrogen is associated with potentially serious adverse effects, including increased risk for developing malignancies of the uterus and the breast. Fortunately, tissue-specific analogues of oestrogen are in development that could specifically target the functions of the brain, and may be devoid of the cancer-inducing and feminising properties of the hormone. Availability of these analogues will make it feasible to treat AD with oestrogen in both women and men. However, findings of preliminary studies, although promising, need to be confirmed in larger, controlled clinical trials before the role of oestrogen in the treatment and prevention of AD can be firmly established.
Geriatric Research, Education and Clinical Center (GRECC) 182 B, Veterans Affairs Puget Sound Health Care System, Seattle/Tacoma, WA, USA. sasthana@u.washington.edu
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