Testosterone Replacement Studied As Alzheimer’s Intervention

A number of studies have indicated that estrogen replacement therapy in postmenopausal women can cut the risk of developing Alzheimer’s disease by up to half. A new report, presented at last month’s American Neurological Association’s annual meeting, suggests that as testosterone levels decrease in aging men, production of a key protein in Alzheimer’s, beta amyloid, increases.

The presentation by Samual Gandy, M.D., Ph.D., a professor of psychiatry at New York University School of Medicine, detailed studies showing that in men who are being treated for prostate cancer and receive medication that suppresses their production of testosterone, blood serum amyloid levels increase dramatically.

Previous studies by Gandy and his colleagues have shown that brain concentrations of amyloid increased significantly in female guinea pigs whose ovaries had been removed. When the animals received hormone replacement therapy, their levels of brain amyloid dropped again.

Other research has linked higher rates of Alzheimer’s to higher levels of serum amyloid, much easier to measure directly. In addition, studies have indicated that women who are taking estrogen replacement therapy have somewhat lower rates of Alzheimer’s. Studies have indicated that estrogen may provide a protective effect by delaying or potentially preventing the onset of the degenerative disease.

Gandy and his coauthor, Ralph Martins, Ph.D., at the University of Western Australia speculated that estrogen and testosterone could play a part in the pathway for development of the disease. They hypothesized that a study could easily be constructed with men whose testosterone levels were suppressed as part of their treatment for prostate cancer. The pair followed six men over a period of six months during which testosterone production was suppressed and found that plasma amyloid levels roughly doubled over the duration of the study.

“It will now be important,” Gandy said in a statement released by New York University, “to follow these measures for several years, while also administering serial cognitive function exams to determine whether any of these men develop Alzheimer’s disease.”

Gandy believes their findings may help to explain why Alzheimer’s is a disease of later life.

“People with a genetic predisposition to Alzheimer’s may have borderline amyloid levels until menopause or the male equivalent, andropause, reduces gonadal hormone secretion. Brain amyloid levels may then rise enough to cause amyloid accumulation to begin.”

As to the effectiveness of hormone replacement therapy in preventing Alzheimer’s, Gandy said a large, 10-year study now under way will yield interim results in 2003. ▪