Testosterone Therapy Linked to Brain Damage in Caucasian Men

A new study from the University of North Texas Health Science Center suggests that testosterone replacement therapy may damage brain function in some white men, but not in men of Mexican heritage.

“Different factors appear to drive dementia,” said the study’s lead author, Rebecca Cunningham, PhD, Assistant Professor of Pharmacology and Neuroscience, in a news release that accompanied publication of the study results. “And these factors are dependent on the ethnicity of the person.”

The study, which was published in the April issue of the Journal of Alzheimer's Disease, sought to determine whether oxidative load predicted testosterone’s effect on brain function.

Using a subset of the Texas Alzheimer's Research & Care Consortium cohort, consisting of Caucasian (n = 116) and Mexican-American (n = 117) men, researchers examined whether circulating total testosterone and luteinizing hormone correlated with cognitive function.

They also assessed whether oxidative stress (as indexed by homocysteine levels) modified this relationship between sex hormones and cognition, and whether levels of 2 antioxidants — superoxide dismutase-1 and glutathione S-transferase (GST) — varied with circulating testosterone.

Among patients with low oxidative stress levels, testosterone correlated positively with GST and produced no detectable harm to brain function.

Among patients with high levels of oxidative stress (homocysteine levels >12 μM), results varied by race.

Testosterone and luteinizing hormone were associated with cognitive impairment in white patients. For Mexican-Americans, however, there was no association, a finding that researchers attributed to that ethnic group’s considerably higher GST levels.

The research team had already done work that found oxidative stress inside an individual’s body affected testosterone’s neuroprotective effects.

Oxidative stress occurs when the body’s production of cell-damaging free radicals outstrips its supply of cell-repairing anti-oxidants.

Research suggests oxidative stress can cause or at least contribute to a wide range of diseases: cancer, Parkinson's disease, heart failure, myocardial infarction, Sickle Cell Disease, autism, chronic fatigue syndrome and, of course, Alzheimer's disease.

The North Texas study is just the latest of several research projects that have raised questions about the potential harm of testosterone replacement therapy.

A study of more than 50,000 men funded by U.S. National Institutes of Health found that seniors who took testosterone drugs had twice as many heart attacks as seniors who did not. The numbers were similar among younger men with a history of heart disease.

A study from the U.S. Department of Veteran Affairs found that taking testosterone therapy was associated with a higher risk of heart attack and death among men with coronary artery disease.

The second study has come under intense fire from clinicians who say that a number of serious errors in the original text undermine its credibility. The US Food and Drug Administration, however, cited the study (along with the NIH study) to justify its decision to perform its own investigation into the cardiovascular risks of testosterone drugs.

Now, the authors of the North Texas study say heart health shouldn’t necessarily be the only concern for patients.

“I would tell Caucasian men to be cautious about taking testosterone, especially if their oxidative stress levels are high,” Cunningham said, noting that a blood test for oxidative stress, such as homocysteine, can help physicians determine good candidates for testosterone replacement therapy.