(February 2001)

Several studies have suggested that estrogen replacement therapy at the time of the menopause can reduce the risk of Alzheimer’s disease or delay its onset. Four other studies suggested estrogens could be useful in treating Alzheimer’s disease. That has resulted in a barrage of advertising directed towards post-menopausal women.

Each of the four estrogen treatment studies were either of brief duration or had only a small number of subjects, or both. A much larger study for a longer period of time was needed. Now that study, involving 32 study sites in the United States and a total of 120 women with mild to moderate Alzheimer’s disease, who were given estrogen in good dosage for one year, has been reported in the February 23, 2000 issue of the Journal of the American Medical Association. Ninety-seven of the women completed the year-long study period. There was no evidence estrogen treatment improved thinking or slowed progression. The authors concluded "this study does not support the role of estrogen in the treatment of Alzheimer’s disease."

Even if estrogens are not effective in the treatment of Alzheimer’s disease, could they prevent the disease from occurring? A useful summary of the ten available studies was reported in the Journal of the American Medical Association in 1998. Taken together, there appeared to be a 29 percent reduced risk of dementia among those who used estrogens, but the results of the individual studies varied a great deal. Three of the studies did show a significant decrease in risk, three others showed a non-significant reduction in likelihood of Alzheimer’s disease, two showed no effect at all, and the final two showed a non-significant increase in risk. All the studies had some methodologic problems. The authors concluded "in summary, the evidence from these observational studies is weak and large, controlled blinded trials are necessary."

Commentary. There is really little convincing clinical data to suggest that estrogens will be useful in the treatment of Alzheimer’s disease. The evidence that women taking estrogens may have a reduced risk of developing Alzheimer’s is intriguing, but clearly preliminary and the studies are so divergent that it is going to take a series of far better designed studies with longer follow-up periods to provide the information that will allow us to make a reasonable judgement.

The cautions about estrogens reducing the likelihood of Alzheimer’s are justified, but there is also some reason for optimism. Only two of the studies were prospective, that is identifying women who chose to take estrogens and those who chose not to take them, and then following them to see who did and who did not develop Alzheimer’s. That is a much better type of study than waiting until women develop Alzheimer’s, then ask who did or did not use estrogens in the past. Both of the prospective studies showed more than a 50 percent reduction in risk for women who took estrogens. There appeared to be no difference in the extent of the reduced risk whether the woman took estrogens for one year or for more than ten years.

Ratings:

Mulnard, R.A. et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer’s disease. Journal of the American Medical Association. Volume 283. (February 23) Pages 1007-1015. 2000.

Yaffee, K. et al. Estrogen therapy in postmenopausal women, Effects on cognitive function and dementia. Journal of the American Medical Association. Volume 279. (March 4) Pages 688-695. 1998.