A new study by UCSF researchers finds that older men with higher testosterone levels performed better on tests of cognition, which suggests that older men who are prescribed testosterone supplements may reduce their risk of cognitive decline, a precursor state to Alzheimer's disease.

Men's bodies tend to produce less testosterone as they age, and some doctors have begun prescribing supplements of the hormone to increase libido and treat other age-related problems in men.

"The men in the study with higher levels of bioavailable testosterone, the testosterone that can reach the brain, did significantly better on these cognitive tests than men with lower levels," said lead author Kristine Yaffe, UCSF assistant professor of psychiatry, neurology and epidemiology and biostatistics, and chief of geriatric psychiatry at San Francisco Veterans Affairs Medical Center.

However, Yaffe does not recommend that men begin taking testosterone to improve cognition. "Our study only looked at natural testosterone levels and so it doesn't prove that testosterone supplements can prevent cognitive decline. We will need results of large randomized clinical trials in older men before we can confidently say that testosterone supplements are beneficial and safe," she said.

Taking testosterone, or over-the-counter supplements that boost levels of the hormone, can have side effects including increased risk of prostate cancer, increased cholesterol levels, acne and male pattern baldness, Yaffe said.

Although some previous studies have suggested that testosterone might benefit the brain, most of these studies were of younger men, she said.

The study, which was published in the April issue of the Journal of the American Geriatrics Society, looked at 300 older men enrolled in a larger study of risk factors for osteoporosis in men that included cognitive testing.

The cognitive tests measured concentration, memory, attention, language, and other cognitive skills. When scores on these tests decline significantly, or are well below average, this serves as a warning of a high risk of Alzheimer's disease, Yaffe said.

In addition to testosterone, the researchers measured estrogen and sex hormone-binding globulin, a protein that binds these two hormones. Although testosterone was linked to better scores on the tests, estrogen had essentially no effect on performance, Yaffe said. Previous studies of women have shown that higher estrogen levels can reduce their risk of cognitive decline.

Other research has shown that men have higher levels of both estrogen and testosterone than women, and that women have a 30 percent greater risk of developing Alzheimer's Disease, Yaffe said. Some researchers hypothesize that women's increased Alzheimer's risk is related to lower hormone levels. This study doesn't explain how testosterone acts on the brain, Yaffe said, but other studies of mice have shown that the parts of the brain that handle learning and memory tasks are replete with receptors for testosterone.

In comparing scores, the researchers focused on bioavailable testosterone, which is not bound to the proteins, Yaffe said, because when the hormone is bound to protein it has essentially no effect on the brain.

Co-investigators on the study included: Joseph Zmuda, assistant professor of epidemiology, and Jane Cauley, associate professor of epidemiology, both at the University of Pittsburgh; and Lilly Lui, from UCSF Prevention Sciences Group.