Estrogen and Alzheimer’s Disease-Part IX

It is generally believed that estrogen has a range of effects on certain systems in the body. This includes the cardiovascular system, the skeletal system and the neuronal system especially those parts involving cognitive functioning. A lot of the evidence comes from animal studies which suggest a neuroprotective role for estrogen and that it may ameliorate the decline in functioning in women with AD.

Epidemiological studies indicate that women live longer with Alzheimer disease than men and that twice as many women have the disease as men. Could it be that vulnerability exists in women following the decline in estrogen production in the postmenopausal phase of life development? Could this information provide some insight into a treatment program for Alzheimer’s disease? These questions passed through researcher’s minds, which led them to undertake research studies to determine the effect of estrogen replacement therapy on cognitive improvement. Several open trial and one randomized study reported results suggestive of the role of estrogen in improving cognition and mood in AD. The difficulty with generalizing from these studies was that they involved a small number of individuals and most did not use standardized diagnostic criteria. At this time, more definitive studies are in progress, which may answer the question of the role of estrogen in AD treatment. These include the Women’s Health Initiative Memory Study, Women’s International Study of Long Term Duration Oestrogen for Menopause and Preventing Memory Loss, and Alzheimer’s with Replacement Estrogens study.

One completed collaborative study with a fairly large sample of subjects was done by Mulnard et al as part of the Alzheimer’s Disease Cooperative Study group. This study investigated the issue "whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate Alzheimer’s disease". The participants, 120 women of advanced age (approximately 75) who had a hysterectomy and have mild to moderate Alzheimer’s disease, were randomized into three groups. This included a control group that got a placebo and two groups of women who received Premarin (the best-selling prescription drug in America) of different dosage. They were followed in this study for twelve months. Caretakers were required to administer the dosages being evaluated and subjects' plasma estradiol levels were taken at each visit to the researcher. The goal was to determine if estrogen alters the downhill course of Alzheimer’s disease.

The results are clear and unequivocal: in older women with mild to moderate Alzheimer’s disease who had a hysterectomy, estrogen does not halt the decline in cognitive function.

This of course does not answer the question of estrogens role in treating Alzheimer’s disease because the study dwelt with a very specific population. It does not tell us whether estrogen taken shortly after the end of menopause could prevent onset, delay its start or diminish the severity of AD. Quoting from the Mulnard study:

Estrogen failed to improve cognitive functional outcomes in this1-year study of women with mild to moderate AD and hysterectomies…we found a benefit of low-dosage estrogen on the MMSE after brief exposure (2 months: P = .05), but the benefit did not persist with continued treatment. In fact, patients receiving estrogen appeared to decline more than those receiving placebo of 1 global clinical measure, the CDR, despite the greater use of donepezil (Aricept) in the estrogen treated patients. Overall the results of this study do not support the role of estrogen in the treatment of AD. (Mulnard , 2000)

The April 4th edition of The Washington Post and The Los Angeles Times carried a report that women taking Premarin in the Women’s Health Initiative study were informed that the drug may put them at higher risk of heart attacks and strokes. This prospective longitudinal study is following 25,000 women and is looking at the role of estrogen in preventing heart disease in healthy women as well as its role in Alzheimer’s disease. Those taking Premerin received a letter indicating a slightly higher incidence of heart attacks, strokes and blood clots had been found when compared to those taking a placebo.

The NY Times, April 5, 2000, reports that "Some heart disease researchers …were wary about estrogen because it can elicit blood clots, which can cause heart attacks and strokes. Birth control pills, which contain estrogen may cause clots, and a recent study found that women who already had heart attacks might not be protected from new ones if they take estrogens."

Future studies must now clarify the role of estrogen in dealing with Alzheimer’s disease and its role in heart disease prevention.


Mulnard RA, Cotmsn CW, Kawas C, van Dyck, CH, Sano M et al. Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease. JAMA 2000; 283(8): 1007-1015

Kolata G. Estrogen tied to Slight increase In Risks to Heart, a Study Hints. NY Times, April 5,2000, Vol. CXLIX: No. 51,349.

To view our other articles on Alzheimer's Disease please view the following:

See: Part I-Medication for Alzheimer's
See: Part II-Clinical Studies of Alzheimer's
See: Part IV-Alternative Treatments for Alzheimer's
See: Part V-Possible New Drugs for Alzheimer's Disease Treatment
See: Part VI-Early Diagnosis
See: Alzheimer's Part VII-Metrifonate
See: Alzheimer's Part VIII-Implications of Longer Life Expectancies
See: Alzheimer's Part IX-Ethical Care Principles
See: Alzheimer's Disease-Part X-Estrogen and Alzheimer's Disease
See: Alzheimer's Disease Part XI-Pocket Smell Test (PST)
See: Alzheimer's Disease Part XII-MAO-B
See: Alzheimer's Disease Part XIII-Critical Flicker Fusion Threshold Test
See: Alzheimer's Disease Part XIV-Donepezil
See: Alzheimer's Disease Part XV-Cerebrolysin
See: Alzheimer's Disease Part XVI-MCI
See: Alzheimer's Disease Part XVII-Summary
See: Alzheimer's Disease Part XVIII-NO Releasing NSAIDs
See: Alzheimer's Disease Part XIX-Vitamin E
See: Alzheimer's Disease-Part XX-Clinical Trials
See: Alzheimer's Disease-Part XXI-The Brain
See Dementia with Lewy's Body- Part XXII-by Gourete Broderick
See: Alzheimer's Disease-Part XXIII-HMG
See: Alzheimer's Disease-Part XXIV-A Prequel
See: Alzheimer's Disease-Part XXV-Psychosis
See: Alzheimer's Disease-Part XXVI- Amyloid-beta Hypothesis Controversy
See: Alzheimer's Disease-Part XXVII- AD and Diabetes
See: Alzhemeir's Disease-Part XXVIII - Insulin and AD



By Harold Rubin, MS, ABD, CRC, Guest Lecturer
April 5, 2000

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