Jan. 26, 2004 -- The evidence is mounting that testosterone may protect men against developing Alzheimer's disease, and now some experts say it may be time for hormone therapy trials to help answer the question once and for all.
A newly published government study links low levels of the male sex hormone as early as a decade before a diagnosis of Alzheimer's with an increased risk for the disease. Researchers with the National Institute on Aging (NIA) say their findings show testosterone protects the aging brain from dementia. But they add that it is far too soon to recommend testosterone therapy for the prevention of Alzheimer's disease.
"There are a lot of concerns about using these supplements," investigator Susan Resnick, PhD, tells WebMD. "Many, many men in the United States are using them, but we have very little information on safety and health outcomes."
Modest Risk Reduction
Resnick and NIA colleagues evaluated testosterone levels over time in 574 men participating in a large ongoing aging study. Using stored blood samples, the researchers were able to identify testosterone levels measured over an average of almost 20 years.
Fifty-four of the men developed Alzheimer's disease during the study. Although testosterone levels fell over time in all men as they aged, these levels dropped more precipitously in men who later developed the disease.
At the end of the study, men with Alzheimer's disease had, on average, about half the levels of testosterone as men without age-related dementia.
The researchers measured 'free' testosterone, which is the active form of the hormone in the body.
For every 10-point increase in testosterone level, there was a 26% decrease in the risk of Alzheimer's disease. This was true even after adjusting for the effect of age, level of education, and other factors that may increase the risk of Alzheimer's disease.
"The strength of this study was that we could go back as long as 10 years prior to a diagnosis of Alzheimer's disease and show that men with higher levels of free testosterone are less likely to develop the disease," Resnick says.
The findings are published in the Jan. 27 issue of the journal Neurology. In the same issue, researchers from Italy reported that lean male and female Alzheimer's patients had low levels of free testosterone when compared with the control group. Editorialists question whether it is time for testosterone prevention trials in men.
More than 1.7 million prescriptions for testosterone were written in the United States in 2002, representing a 30% increase over 2001 and a 170% increase over 1999, according to figures from the National Academy of Sciences' Institute of Medicine. Older men are increasingly taking the hormone in an effort to stop the clock and prevent conditions associated with aging, even though the medical evidence for this is weak.
Last November, an Institute of Medicine task force came out against large-scale testosterone prevention trials similar to the estrogen replacement therapy trials in women. Instead, the group recommended smaller trials involving only older men who had been diagnosed with low testosterone and who are not at high risk for prostate cancer.
Just as long-term estrogen replacement therapy in older women has been linked to an increased risk of breast cancer, there are concerns that men who take testosterone may be increasing their prostate cancer risk.
Alzheimer's expert Samuel Gandy, MD, PhD, says the hope is that scientists will develop a "designer" testosterone that would target the brain and not affect other organs, in the same way the designer estrogen-like compounds, such as Raloxifene (Evista), targets the bones to prevent osteoporosis.
"Theoretically we could develop a designer estrogen or testosterone that could be protective against dementia," he says.
The Alzheimer's Association spokesman, who runs the Farber Institute for Neurosciences at Philadelphia's Thomas Jefferson University, says the long-term risks vs. benefits of taking testosterone to prevent dementia will not be known until clinical trials are completed.
"Until that happens there is no medical justification for taking testosterone to lower the risk of Alzheimer's," he says. "The data just aren't there to support that as a recommendation."