YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==ESTROGEN AND ALZHEIMER'S== 2 AUTHOR Fillit H TITLE Future therapeutic developments of estrogen use. SOURCE J Clin Pharmacol; VOL 35, ISS 9 Suppl, 1995, P25S-28S ABSTRACT The potential long-term benefits of estrogen replacement therapy (ERT) in the prevention of osteoporosis and heart disease have been reasonably well established. However, the favorable effects of ERT on cognitive function and prevention of senile dementia in old age now represents a revitalized area of clinical research. A growing body of experimental evidence has recently provided the neurobiologic basis to support the hypothesis that gonadal hormones such as estrogen have psychologic effects on human brain function and behavior. Studies in women who have undergone surgical menopause have demonstrated that the menopause is associated with subclinical cognitive and affective dysfunction, which is improved by ERT. In addition, a growing body of evidence suggests that estrogen may be an effective therapy for senile dementia in some elderly women. Recent epidemiologic studies have indicated that long-term postmenopausal ERT may prevent late-life cognitive dysfunction in older women. Several clinical trials employing oral estrogen therapy have also observed that some aged women with senile dementia have improved cognitive and affective function after estrogen therapy. Estrogen loss resulting in cognitive disorders, including menopausal cognitive dysfunction and senile dementia in late life, may act via several mechanisms. Estrogen may be an important growth factor for estrogen-responsive neurons. Estrogen therapy may also have substantial neurochemical effects, direct effects on the vasculature, and effects on the generation of free radicals, which may be toxic to neurons. At this time, several important clinical questions need to be answered regarding the role of ERT in the cognitive and affective dysfunctions associated with menopause and senile dementia. Should estrogen be used for menopausal women whose sole complaint is cognitive or affective dysfunction? Does long-term ERT prevent cognitive decline in late life if initiated at the time of menopause? Can ERT improve cognition and affective function in postmenopausal women with Alzheimer's disease, and does estrogen therapy prevent the progression of Alzheimer's disease in these patients? Finally, do the vascular effects of estrogen play a role in the treatment or prevention of both Alzheimer's disease and vascular dementia? 4 AUTHOR Lobo RA TITLE Benefits and risks of estrogen replacement therapy. SOURCE Am J Obstet Gynecol; VOL 173, ISS 3 Pt 2, 1995, P982-9 (REF: 33) ABSTRACT Estrogen replacement therapy (ERT) has been shown to reduce the risk of cardiovascular disease (CVD) and osteoporosis in postmenopausal women. Studies also indicate a reduced risk of stroke and its consequent mortality among estrogen users, and ERT may also have a role in reducing the risk of Alzheimer's disease and increasing a woman's overall quality of life. On the negative side, some studies show a small duration-related risk of breast cancer with estrogen use and a significant increase in endometrial cancer; the latter is virtually eliminated with the addition of a progestin to the regimen. Although the definitive answer is not yet available, recent epidemiologic data suggest no reduction in protection against CVD and bone fracture with the addition of progestin, which is referred to as hormone replacement therapy, as opposed to using estrogen alone. A woman's potential risks associated with ERT or hormone replacement therapy must be weighed against her lifetime risks of developing CVD, stroke, and bone fracture. The reduction in mortality and morbidity rates with hormone use is generally viewed to be substantial and cost-effective. Health care professionals have an important role in shaping their patients' attitudes. Patients need more information from their physicians about the risks and benefits of estrogen therapy. 5 AUTHOR Honjo H AUTHOR Tanaka K AUTHOR Kashiwagi T AUTHOR Urabe M AUTHOR Okada H AUTHOR Hayashi M AUTHOR Hayashi K TITLE Senile dementia-Alzheimer's type and estrogen. SOURCE Horm Metab Res; VOL 27, ISS 4, 1995, P204-7 (REF: 32) ABSTRACT Some reports have suggested the ameliorative effects of estrogens on clinical symptoms, such as short memory, in women suffering from senile dementia-Alzheimer's type, in vivo. The action mechanism of estrogen remains to be clarified, but 1) an anti-depressive effect, 2) improvement of cerebral blood flow, 3) direct stimulation of neuron, 4) development of gliacyte and 5) suppression of apolipoprotein E have been suggested. Some mechanisms may be combined, contributing to the beneficial effects on clinical symptoms. 6 AUTHOR Tang MX AUTHOR Jacobs D AUTHOR Stern Y AUTHOR Marder K AUTHOR Mayeux R AUTHOR et al TITLE Effect of estrogen during menopause on risk and age at onset of Alzheimer's disease SOURCE Lancet; VOL 348 ISS Aug 17 1996, P429-432, (REF 28) ABSTRACT IPA COPYRIGHT: ASHP To investigate whether estrogen use during the postmenopausal period affects the risk of developing Alzheimer's disease, a study was conducted in 1124 non-demented elderly women (mean age 74.2 yr and mean duration of education 9.2 yr), who were initially free of Alzheimer's disease, Parkinson's disease, and stroke, and were participating in a longitudinal study of aging and health in a New York City community follow-up; in the study group, 36% were African American, 38% were Hispanic, and 26% were Caucasian. Follow-up ranged from 1 to 5 yr. Overall, 156 (12.5%) women took estrogen after the onset of menopause. The age at onset of Alzheimer's disease was significantly later in women who had taken estrogen, and the relative risk of the disease was significantly reduced (5.8% estrogen users vs 16.3% nonusers), even after adjustment for differences in education, ethnic origin, and apolipoprotein-E genotype. Women who had used estrogen for >1 yr had a greater reduction in risk.