MONDAY, Jan. 26, 2004 (HealthDayNews) -- Low levels of testosterone are linked with a higher risk of developing Alzheimer's disease, a new study claims.
In a large group of men, researchers looked at the levels of free testosterone, which is the amount of testosterone circulating in the blood.
The researchers found a 26 percent decrease in the risk of Alzheimer's for every 50 percent increase in the amount of free testosterone measured in the blood. While levels of testosterone do decrease with age, levels dropped significantly more in men who developed Alzheimer's.
In addition, men who developed Alzheimer's had about half the amount of testosterone compared to men who didn't get the disease. And for some men, this drop in testosterone was found 10 years before Alzheimer's was diagnosed, according to the report in the Jan. 27 issue of Neurology.
"This is one more piece that we need to understand whether testosterone will protect men from developing Alzheimer's disease," says study author Dr. Susan Resnick, an investigator with the National Institute on Aging (NIA). "The logical next step would be to see if men should be raising their levels of testosterone. We don't know the answer to that yet."
In the study, 574 men were followed for about 19 years as part of the Baltimore Longitudinal Study of Aging. Their testosterone levels were checked periodically, and none of the men had Alzheimer's at the beginning of the study. During the follow-up period, 54 of the men developed Alzheimer's disease.
In earlier studies, Resnick and her team found older men with high levels of free testosterone have better visual and verbal memory and perform spatial tasks better then men with lower levels of testosterone.
"In the current study, we found that higher levels of free testosterone were associated with a significant reduction in the risk for Alzheimer's disease," Resnick says.
However, Resnick adds it is a complicated problem, and simply raising testosterone levels might not do the trick. "There may be some optimal level of testosterone that is beneficial, but levels that are too high or too low may not be beneficial," she explains.
Resnick also points out that some studies have shown estrogen may protect women from Alzheimer's. Of course, other studies have shown that women taking both estrogen and progestin are at greater risk for all types of dementias, she adds.
When testosterone crosses into the brain, it can be converted to estrogen, Resnick notes. "So we don't know if all those things related to estrogen in the brain are responsible for this effect or whether it is testosterone itself," she says.
Resnick says that more and more men are taking testosterone supplements, but she warns that little is known about the potential risks. For example, taking testosterone may increase the risks for prostate cancer and stroke, she says.
"This is an area that is worth exploring, but you should not go out and take testosterone supplementation assuming that it is going to be a good thing," Resnick cautions. "We certainly do not encourage anyone to use testosterone supplements to improve memory or prevent Alzheimer's disease."
According to Resnick, the NIA is considering doing small-scale clinical trials of testosterone replacement therapy in older men. These trials may begin soon.
Another study in the same journal issue also looked at the role of another player in Alzheimer's disease. Italian researchers found sex hormone-binding globulin, which is a protein that transports testosterone and estradiol in the blood, was significantly higher in men and women with Alzheimer's disease compared with normal subjects.
The researchers looked at 64 women and 32 men with Alzheimer's disease and compared them with similar men and women who did not have the disease.
The researchers, led by Dr. Gian Benedetto Melis, chairman of the department of obstetrics and gynecology at the University of Cagliari, believe factors involved in increasing levels of sex hormone-binding globulin could have an important role in lowering levels of testosterone as seen in patients with Alzheimer's disease.
Eva Hogervorst, an associate professor at the University of Arkansas for Medical Sciences and co-author of a journal editorial, comments that in her own studies she has found Alzheimer's patients had slightly lower levels of testosterone compared with healthy patients, but primarily they had significantly higher levels of sex hormone-binding globulin.
Hogervorst believes the key connection is not between low levels of testosterone and Alzheimer's, but rather between high levels of sex hormone-binding globulin and Alzheimer's, as found in the study by Melis' group.
"If you lower levels of sex hormone-binding globulin, more testosterone would be available for the brain, which might have a beneficial effect," she says.
Whether lowering sex hormone-binding globulin levels would prevent Alzheimer's has never been shown, and studies need to be done, she says. There may also be unwanted side effects such as increasing the risk for prostate cancer and stroke, Hogervorst cautions.
"Despite all the biological possibility, the proof of the pudding will be the results of large, controlled trials," she adds.
Hogervorst advises men to "hold your horses -- don't go running out to your doctor and ask for treatment just yet. We need to do a lot more research before recommending lowering sex hormone-binding globulin as a widespread treatment for preventing Alzheimer's disease."
More information
For more on Alzheimer's disease, visit the Alzheimer's Association or the Fisher Center for Alzheimer's Research Foundation.
