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| The Use of Estrogen To Treat
Alzheimer's |
Estrogens can work in several ways
to slow or prevent nerve cell death in Alzheimer disease. They may have a
direct protective effect on the nerve cells themselves, they may prevent
cerebrovascular disease, they can improve cerebral glucose transport, and they
may reduce the formation of ß-amyloid plaques.
Numerous epidemiologic studies have suggested that
postmenopausal estrogen replacement is associated with a reduced risk of
subsequent Alzheimer disease
Odds
ratios for estrogen-users of 0.7, 0.5, 0.4 to develop Alzheimer disease are not
individually statistically significant, but taken together they indicate a
protective benefit.
Much less is
known, however, about whether estrogen administration can be used to treat
patients with establish Alzheimer disease.
A recent review has examined the available
clinical evidence that estrogen therapy alleviates the disease. Only two
randomized, placebo controlled studies were reported up to 1996. In the first,
published in 1954, estradiol (2 mg) was given weekly intramuscularly to 13 of
28 women in a residential home over 18 months, with testosterone (20 mg) added
to reduce uterine bleeding after the first 6 months.
Significant improvements were found over
placebo in the verbal IQ, comprehension and memory on the Wechsler-Bellevue
Intelligence subscale scores of the women given the estrogen for 12 months.
In the second controlled study,
published in 1973, 25 of 50 women received conjugated estrogens (0.625 mg of
Premarin?) for 3 weeks in every 4, over a 3-year period. Very similar results
were obtained to those of the first trial. It seemed that estrogen improved
cognitive performance over a period of 12 months, after which the underlying
disease process resumed its downhill course.
Other trials of the possible beneficial effects of
estrogen treatment have provided stimulating but non-conclusive results,
because of their open design, small patient numbers, and the use of patients
with a measurable degree of depression.
While further large well-controlled studies
of estrogens in the treatment of established Alzheimer disease are clearly
needed, the increasing use of hormone replacement therapy in women - for a
variety of clinical indications - may make it difficult to recruit subjects for
such prospective studies. Moreover, it may be difficult to design trials in
which men with Alzheimer disease are treated with estrogen.
Combination of estrogen treatment with
other drug interventions should also be studied – these drugs may prove
additive in delaying what is currently regarded as almost inevitable
deterioration.
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