Mental Health special section

Free testosterone dukes it out with AD

The male hormone seems to cut AD risk. It also does a
lot of other things that aren't nearly so attractive

By Jadzia Jagiellowicz

Mr Samson has just come into your office. He's 68 years old. He complains that he is forgetting people's names and worries he might have Alzheimer's disease (AD). Then comes the kicker. He tells you he's just read that low testosterone can lead to Alzheimer's and wants you to prescribe testosterone therapy. You see from his chart that he has benign prostatic hyperplasia. Should you comply with his request?

Mr Samson has based his conclusions on results of a study funded by the National Institutes of Health (NIH), and published in the January 27 issue of the journal Neurology. According to Dr Susan Resnick, one of the authors of the study and an investigator at the National Institute on Aging (NIA) in Baltimore (part of the NIH), the study found that the risk for AD decreased by 26% for every 50% increase in free testosterone levels in the bloodstream. Importantly, the free testosterone measures were gathered two, five and 10 years before the onset of AD, indicating that lower free testosterone levels may contribute to but not be the result of AD. At baseline the assay free testosterone index (nMol/nMol) was 0.2 for both the patients who went on to develop AD and those who did not. At the end of the study that level remained the same for the non-AD group, but in the patients who developed AD the level dropped by 50%, to 0.1.

The study analyzed data from 574 men who had participated in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA had measured the androgen levels of these men, who ranged in age from 32-74 years, at various times over an average of 19 years. The testosterone study calculated the levels of free testosterone in the men's bloodstreams. Testosterone in the body tends to attach itself to sex hormone binding globulin. However, some remains unbound and circulates as free testosterone. The AD diagnosis was based on the results of laboratory and imaging assessments as well as neurological and neuropsychological exams. Using criteria in the Diagnostic and Statistical Manual of Mental Disorders, 54 men in the study developed AD.

Do the results provide enough evidence to warrant the clinical use of testosterone therapy in Mr Samson in order to prevent AD? Dr Resnick doesn't think so. "This kind of study is not going to predict [the risk of AD] for an individual," she said. Rather than being used for individual predictions, Dr Resnick suggested that observational studies such as this one could help guide and focus investigators on the important measures to keep in mind as they consider further research areas.

Her suggestion has been heard. Based on the results of this study, a multidisciplinary panel, led by the Institute of Medicine in the US and supported by the NIA, has recommended that researchers begin small-scale clinical trials of testosterone therapy for symptomatic older men with low testosterone levels. Dr Evan Hadley, associate director of the NIA's Geriatrics and Clinical Gerontology program, was unaware of any such initiatives in Canada, however.

A Canadian expert on AD is cautious about assuming that findings from an epidemiological study such as Dr Resnick's would translate into similar findings in a prospective clinical trial. "Lower testosterone levels could be part of a number of factors accelerating the Alzheimer process," said Dr Serge Gauthier, Director of the Alzheimer and Cognitive Disorders Clinic at the McGill University Centre for Studies in Aging.

Although the evidence is inconclusive, scientists also have concerns that testosterone supplements may increase the risk for prostate cancer or stroke, noted Dr Resnick. Dr Gauthier echoed her concerns: "It is far from certain that testosterone supplementation would be safe and effective in delaying the onset of AD."