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12 October 2001
When Testosterone Drops, Alzheimer's Increases
by George Atkinson

When doctors suppress testosterone levels in men with prostate cancer, they may inadvertently be increasing the level of a substance implicated in Alzheimer's disease, according to a report presented at the American Neurological Association's 126th annual meeting, September 30 to October 3 in Chicago.

The study indicates that when testosterone levels go down, there is a dramatic increase in levels of a protein known as "amyloid," the prime suspect in the death of nerve cells in Alzheimer's disease.

"We believe that this phenomenon may explain why Alzheimer's disease occurs in late life. People with a genetic predisposition to Alzheimer's may have borderline amyloid levels until menopause or the male equivalent, andropause, reduces gonadal hormone secretion. Brain amyloid levels may then rise enough to cause amyloid accumulation to begin," said author Sam Gandy, M.D., Ph.D., of New York University.

A number of studies have found that hormone replacement therapy in postmenopausal women cuts the risk for Alzheimer's disease in half, leading Gandy, coauthor Ralph Martins, PhD., of the University of Western Australia, and their colleagues to speculate that gonadal hormones such as estrogen and testosterone might help to break down amyloid.

Although it has not been proven, a wealth of evidence suggests that the accumulation of amyloid into clumps called "senile plaques" is toxic to nerve cells. On autopsy of Alzheimer's patients, doctors find especially high numbers of senile plaques in brain areas that underlie memory and reasoning, brain functions that deteriorate dramatically in the disease.

Previous studies by Gandy and his colleagues showed that brain concentrations of amyloid increased significantly in female guinea pigs whose ovaries had been removed. When the animals received hormone replacement therapy, their levels of brain amyloid dropped.

The researchers realized that a natural experiment could be conducted with men whose testosterone levels are suppressed as part of their treatment for prostate cancer.

"In each of six men, when testosterone levels were suppressed, plasma amyloid levels roughly doubled over the six months' duration of the study," said Gandy.

Other researchers have shown that people with higher levels of amyloid circulating in the blood are more likely to get Alzheimer's. For that reason, said Gandy, "It will now be important to follow these measures for several years, while also administering serial cognitive function exams to determine whether any of the men develop Alzheimer's disease."

As for the effectiveness of hormone replacement therapy in preventing Alzheimer's, said Gandy, a large, ten-year study currently underway will yield five-year interim results in 2003.

"If hormones are proven to be effective in this trial, then prevention of Alzheimer's disease may become an indication for hormone replacement therapy in both men and women," said Gandy.

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