Shocking, but potentially promising way to treat Alzheimer's - Lupron

July 22nd 2006

Lupron

For the last several years, the main drug used to treat Alzheimer's
disease has been Aricept, but its benefit isn't long-lasting, spanning
maybe 18 months to 2 years. Yet surprisingly, a randomized study out
just this week has added another clue to the mystery of this tragic
disease - a drug called leuprolide (brand name Lupron) commonly used
to treat prostate cancer, breast cancer, and endometriosis was found,
after 12-48 weeks, to significantly slow the progression of
Alzheimer's.

Lupron's mechanism of action is that it blocks LH (luteinizing
hormone), which prompts the pituitary gland to produce gonadotropins,
hormones that stimulate the ovaries and testes to produce the high
levels of estrogen and testosterone necessary for reproduction.

This drug is given as a shot and helps to treat recurrent fibroids or
endometriosis and is used as a way to induce temporary menopause in
early and late stage breast cancer patients; it also shuts down
testosterone production in men with prostate cancer.

The baffling thing about this new, yet inconclusive, Alzheimer's study
to some scientists is how this observed benefit could possibly be
real, since this is a drug that blocks the "brain protective" hormones
estrogen and testosterone. However, if researchers are truly following
all of the current, available evidence surrounding hormones' effects
on cognition, this study should NOT be a surprise! In fact, a lot of
valid scientific evidence points to the contrary, that excessively
high levels of reproductive hormones throughout life may be bad for
the brain.

The most conclusive data to date, at least in women, comes from (yet
again) the WHI (Women's Health Initiative) which surprised everyone
when the trials found stroke and memory risks (including dementia) for
women on estrogen or estrogen/progestin. While this study may have
been a shock, there were other observational data out years before
this study that spelled trouble. The Rotterdam study, for example,
evaluated the natural estradiol levels of older women to see if there
was any association with cognition. Surprisingly, the women with the
highest levels had a doubled incidence of vascular dementia and a
slightly greater risk of Alzheimer's.

In April 2000, another study conducted by Terry Manolio of the
National Heart Lung and Blood Institute, looked at the MRIs of the
brains of 2000 women, half of whom were taking estrogen. Again, the
estrogen users' brain scans showed slightly more decay than the non-
users. Dr. Manolio herself didn't know what to make of this and
worried that this would scare women off of their hormone replacement
since it was basically a given that the therapy was beneficial! Also,
a laboratory study out of Emory that went virtually unnoticed involved
sophisticated cognitive tests of older female cynamalgous monkeys who
either retained their ovaries or had them removed at a young age.
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This study, according to the scientists, actually found a PROTECTIVE
effect of ovary removal on spatial-visual memory in the older monkeys.
And lastly, a small study out from Urbana-Illinois, reported this
Janurary, showed that high levels of fitness counteracted the
cognitive decline associated with longterm HRT use. Again using brain
MRIs of 54 women, this study found that those who used HRT for 10+
years had decreases in the 4 different areas of gray matter in the
brain, but that exercise lessened these decreases. While only the WHI
is truly definitive out of all these studies, it seems clear that
hormones do not have any preservative effects on thinking and
cognitive abilities.

Based on this data, hormonal decline with age should no longer be
viewed as a bad thing, but rather a natural protective mechanism.
Secondly, attempting to replace hormones is fraught with multiple
hazards. Third, the healthiest lifestyles are those which actually
lessen the effects of reproductive hormones on the body's organ
systems. Obesity, which is a risk factor for heart disease, colon and
reproductive cancers, and probably dementia, is a condition involving
excessive estrogens and androgens.

Exercise and a diet than keeps weight down have long been known to be
beneficial, although the precise mechanisms haven't been clearly
pinpointed. Hypothetically, it may be a hormone lowering effect.
Taking all of this into account, it seems that scientists should have
enough basis to be pooling their efforts into exploring the effects of
hormonal manipulation as a way to prevent/treat Alzheimer's, stroke,
and other serious brain degenerating diseases.

A word of caution in all this - to espouse the widespread, longterm
use of drugs that BLOCK hormones (be it Lupron or whatever else comes
along) is just as bad an idea as HRT was!! Both are clearly
disrespectful toward the natural intricacies of human biology.
Instead, a more accurate interpretation (at least in terms of this
latest Alzheimer's research) is that both menopause in women and the
natural age related androgen decline in men do not trigger the aging
process but are instead inherent natural processes that PROTECT us
from diseases. And Alzheimer's, perhaps the scariest of all, might
just be one of them. We now know that hormones don't need replacing.
And we also have good reason, at least from a hormonal standpoint, to
be espousing widespread modalities aimed to lessen the overweight
epidemic in this country, considering all of the various other
diseases associated with it. Conclusive answers are not yet in, but
the puzzle is certainly coming together.

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