Like estrogen loss in older women, decreased levels of testosterone may put aging men at risk for Alzheimer’s disease, according to a new study by USC researchers.

The team’s findings—appearing as a letter to the editor in the Sept. 22 issue of the Journal of the American Medical Association—bolster sparse research on the adverse effects of age-related testosterone depletion in the brain and may lead to future development of hormone replacement therapies.

“Our findings strongly suggest that normal age-related testosterone depletion is one of the important changes that promote Alzheimer’s disease in men,” said Christian Pike, senior author of the study and an assistant professor at the USC Leonard Davis School of Gerontology.

“Understanding how these changes increase vulnerability to the disease is critical not only for elucidating Alzheimer’s development, but also for identifying those persons most at risk,” Pike said.

While the link between estrogen loss in women and increased susceptibility to a variety of diseases—including Alzheimer’s—has long been established, there has been less focus on the health effects of hormonal depletion in men.

Only within the last few years has the range of impairments—including osteoporosis and the loss of muscle mass, strength and function known as sarcopenia—and their link to decreased testosterone levels become a recognized clinical syndrome called ADAM, or androgen deficiency in aging males. Androgens are male sex hormones.

The data collected by the USC team—Pike, Lilly Chang and Frank Stanczyk of the Keck School of Medicine, and Emily Rosario of the USC Andrus Gerontology Center—suggest that the brain is another tissue that experiences age-related testosterone loss and that increased vulnerability to Alzheimer’s disease should now be considered a component of ADAM.

Using brain tissue from 45deceased male subjects and an established medical scale of neuropathology, the researchers divided their samples into three categories: those considered neuropathologically normal with no clinical history of cognitive impairment (these were the controls); those who exhibited mild neuropathological changes; and those who had Alzheimer’s disease.

“We found that brain levels of testosterone are significantly lower in [Alzheimer’s] subjects compared with the control subjects,” the researchers wrote. “We found that brain levels of testosterone are also significantly reduced in men with mild neuropathology consistent with early Alzheimer’s disease.”