Sex (Hormones) on the Brain

Study finds testosterone may stave off Alzheimer's damage

FRIDAY, Aug. 17, 2001 (HealthDayNews) -- Women are up to three times more likely than men to get Alzheimer's disease -- and a group of Canadian researchers think they know why.

The key, they say, is the male hormone testosterone. Their new study shows testosterone can protect the brain from cell death related to Alzheimer's.

"Women begin losing their reproductive hormones, including not only estrogen but also testosterone, in middle age, while most men don't see a decline in their reproductive hormones, particularly testosterone, until they are well into their 80s," says Dr. Morrie Gelfand, study author and professor of obstetrics and gynecology at Canada's McGill University.

It may not be entirely coincidental, says Gelfand, that the risk of Alzheimer's in men only goes up when testosterone levels go down -- around age 84.

"We have shown in the lab that testosterone does, in fact, protect against cell death or apoptosis, which is the biological event that occurs in Alzheimer's," says Gelfand.

Perhaps men avoid this disease more readily, Gelfand adds, because they simply have a greater supply of testosterone protecting their brain from cell death.

Other experts say, however, that it's a giant leap from the Petri dish to the human body.

"The decrease in testosterone in men -- or in post-menopausal women -- is so subtle, it's hard to imagine that this small degree of change could have such a powerful impact on the brain cells," says Charles Mobbs, an Alzheimer's researcher who is also an associate professor of neurobiology and geriatrics at the Mount Sinai School of Medicine.

To make the connection valid, says Mobbs, "We would need evidence that the levels of testosterone in men with Alzheimer's disease are actually lower than in men who do not have this disease -- and that the same holds true for women. And right now, we just don't know that."

Alzheimer's disease is a condition in which brain cells deteriorate and eventually die, taking with them many important life functions, beginning with memory.

Because women develop Alzheimer's at triple the rate of men, one theory holds that the dramatic drop in estrogen experienced at mid-life may be behind the onset of this disease in those who are susceptible.

But Gelfand believes an older woman's slight dip in testosterone is responsible for the increased risk.

"It seems reasonable to assume that keeping testosterone levels normal longer could give women the same protection that men seem to naturally have well into their senior years," he says.

The study, published in a recent issue of The Journal of Neurochemistry, used the human brain cells of 12-to-16-week-old fetuses. The fetal brain tissue was obtained in accordance with the guidelines established by the Medical Research Council and approved by the Institutional Review Board of McGill University.

The cells were separated into two groups and treated with various chemical processes designed to encourage cell death. In one group, however, the cells were also treated to one of three different hormone "baths," which contained testosterone, methyltestosterone (a synthetic form sometimes used for male hormone therapy) or epitestosterone (an inactive natural form of testosterone). Each of the hormones was applied directly to the cells in levels equal to that which occurs in the body naturally during peak reproductive years.

Although all three hormones showed some protective effects, Gelfand says it was testosterone that offered the most hopeful result.

"It virtually kept the cells alive the longest, and it accomplished this at levels equal to what is found naturally," says Gelfand.

His theory: giving men and women testosterone replacement therapy as soon as their natural levels start to drop off could dramatically reduce the risk of Alzheimer's disease.

Mobbs, however, is not convinced. "I believe the in vitro results, but the physiology of aging and testosterone does not make it a really good candidate for this kind of replacement [therapy]."

Women who take testosterone can wind up with increased muscle mass, facial hair, male pattern baldness, breast shrinkage, lowering of the voice and other side effects.

In the end, Mobbs says, it is doubtful that any of the reproductive hormones will have any influence on the development of Alzheimer's disease.

What To Do

Both experts caution that if you are interested in pursuing testosterone therapy, you should do so only under the personal guidance of a physician. Do not, they warn, buy any over-the-counter testosterone products, those that may be available on the Internet or elsewhere without a prescription.

"This is a drug, and it is not entirely without side effects. No one should take it without careful medical monitoring," says Mobbs.

To learn more about the symptoms of Alzheimer's disease, visit the Alzheimer's Association. For a listing of clinical trials testing a variety of treatment approaches, click here.

For more information on testosterone therapy, click here. For information on the use of testosterone in women, check out the news report found here

SOURCES: Interviews with Morrie Gelfand, M.D., professor of obstetrics and gynecology, McGill University, Montreal, and Bloomfield Center for Research in Aging, The Lady Davis Institute for Medical Research; Charles Mobbs, Ph.D., associate professor, Center For Neurobiology and Geriatrics And Adult Development, Mount Sinai School of Medicine; June 2001 Journal of Neurochemistry
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