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Drop in Men's Testosterone Might Lead to Alzheimer's

Study finds falling sex hormone levels could trigger the disease

THURSDAY, Nov. 1, 2001 (HealthDayNews) -- A new study by New York University researchers holds promise for identifying the role of sex hormones in the onset of Alzheimer's disease.

Dr. Sam Gandy, a professor of psychiatry and cell biology at New York University School of Medicine, made the discovery as part of a small study that followed six men undergoing testosterone suppression for treatment of prostate cancer.

After the hormone levels were reduced, a protein called amyloid roughly doubled. Researchers believe amyloid accumulation leads to the build-up of "senile plaque" that kills nerve cells controlling memory and reasoning. Gandy reported his results at a recent meeting of the American Neurological Association.

Previous studies have indicated that postmenopausal women who take estrogen cut their risk of Alzheimer's by half; this is the first study to look at the role testosterone plays in men.

Gandy says the research offers an important clue to the reason that Alzheimer's strikes the elderly. If sex hormones keep amyloid from building up, it makes sense that menopause or andropause (menopause's male equivalent) could be the trigger for the degenerative, fatal disease.

"Falling hormone levels may be the straw that breaks the camel's back," Gandy says. "We would suggest that when it occurs in people who might have marginal metabolism of amyloid, perhaps menopause or andropause might tip them over."

The new study is significant because it's the first time Alzheimer's researchers have looked at the role of sex hormones in men, says Dr. Allan Levey, a professor at the Emory University School of Medicine in Atlanta and the director of the Emory Center for Neurodegenerative Diseases.

"There's some association between the use of estrogen postmenopausally and Alzheimer's," Levey says. "There hasn't been that body of evidence yet implicating testosterone, in part because people haven't been looking. It's been ignored. The attention of Sam Gandy's group is raising some important questions."

Levey says the results of this study "won't change the way I think about Alzheimer's in men" because of the study only involved six patients, but he'll be following further studies closely.

"Doubling the level of amyloid-beta is not trivial," he says. "It's a pretty substantial increase. But as yet, it's early. I'll be interested to see if more evidence emerges."

With this initial data, Gandy says his team is now extending its study to larger numbers of men and including "very rigorous mental cognitive function testing" in the study model. They also are trying to find "both the parts of the cell and particular molecules that hormones are using to cause this effect."

"Our notion is once we do that, we should be able to design drugs that might target those same pathways but not have the side effects of hormone replacement," he says.

Side effects of hormone replacement therapy for women can include bloating, breast tenderness, cramping, irritability, depression, and sometimes spotting or a return of monthly periods. It also is implicated in an increased risk of endometrial and breast cancer and blood clots.

Gandy and Levey emphasized that with the very small numbers in this study, no one who is undergoing hormone suppression for the treatment of prostate cancer should stop.

"There's no clear link yet -- get the prostate cancer treated," Levey says. "The immediate future would be larger studies, continued interest and a lot of questions that need to be answered."

All of that is happening, Gandy says. The data on the role of amyloid in Alzheimer's is so promising that almost every pharmaceutical company in the country is studying it. And they have a good reason: The disease affects 10 percent of those over 65 and half of those 85 and older, he says.

"Amyloid is the best-guess target for drug therapy," Gandy says, "either for slowing its accumulation or accelerating its clearance. I expect to see effective treatment [for Alzheimer's], if not prevention and a cure, in my lifetime."

What To Do: For more information on Alzheimer's disease, visit the Alzheimer's Association or the Alzheimer's Disease Education and Referral Center, a service of the National Institute on Aging.

SOURCES: Interviews with Sam Gandy, M.D., Ph.D., professor of psychiatry and cell biology, New York University School of Medicine; Allan Levey, M.D., Ph.D., professor of neurology, psychiatry and behavioral sciences and pharmacology, Emory University School of Medicine, and director, Emory Center for Neurodegenerative Diseases, Atlanta; American Neurological Association release
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