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Testosterone-replacement therapy may increase risk of brain damage in Caucasian men. That was the conclusion of a recent study published in the Journal of Alzheimer’s Disease, which evaluated the influence of oxidative stress on testosterone’s typically protective effects.

Usually, testosterone helps protect the brain against factors that can cause dementia or Alzheimer’s disease, including free radicals, which can damage brain cells, affecting memory and cognitive skills. But in men already suffering from oxidative stress, an excess of testosterone—which can occur when taking testosterone-replacement therapy—can actually make the situation worse.

Studies Link Testosterone Therapy to Cardiovascular Risk

In January 2014, the FDA released a safety communication stating that they were investigating testosterone replacement therapy and its potential to increase the risk of heart attack, stroke, and death. They based the communication on the results of two studies that suggested the therapy increased risk of adverse cardiovascular events in men.

The first study was published in the Journal of the American Medical Association (JAMA) in November 2013. Men who received testosterone treatment had a 30 percent increased risk of stroke, heart attack and death, compared to those who had not received the therapy. The second study was published in PLOS One in January 2014, and reported a two-fold increase in the risk of heart attack in men 65 years and older in the first 90 days of the treatment. Men younger than 65 who were already at risk of heart disease also had a two- to three-fold increased risk of heart attack in the first 90 days.

Since these studies were published, many men have come forward with claims against the manufacturers of these drugs in testosterone therapy lawsuits. They note that the companies failed to provide adequate warnings about the risks, and also overpromoted the therapy to men who may not have really needed testosterone replacement.

Studies Find Low Levels of Testosterone Increase Risk of Alzheimer’s

In 2010, a study out of Saint Louis University found that having a low testosterone level put older men at risk of Alzheimer’s disease. An earlier 2004 study found similar results. Older men with lower levels of free, unbound testosterone circulating in their bloodstreams were found to be at a higher risk of developing Alzheimer’s disease. For every 50 percent increase in the amount of free testosterone, there was about a 26 percent decrease in the risk of developing the disease.

The researchers stopped short of recommending testosterone therapy to reduce risk of the disease, stating they still had so much to learn, and that the side effects of hormone therapy were uncertain.

What is Oxidative Stress?

As a result of this recent study, we know that too much testosterone may also be damaging. Scientists at the University of North Texas (UNT) Health Science Center, testosterone products in Caucasian males may actually increase risk of brain damage and dementia, though no such effect was found in Mexican-American men.

According to a report released by the Center, in Caucasian men who have elevated levels of oxidative stress in the brain, testosterone replacement therapy increases risk of damage to brain cells. They add that “Many studies have found between 20 percent and 30 percent of aging men have no response or a negative response to testosterone therapy.”

What is oxidative stress? Like factories, humans produce by-products when manufacturing energy from food. These by-products are called “free radicals,” and are usually neutralized by antioxidants, which are naturally present in the body, and are also present in vitamins, minerals, and phytochemicals from the fruits, vegetables, and other items in our diets.

As we age, the theory goes, we may start to lose the battle with free radicals. A poor diet, disease, smoking, and other lifestyle factors can also tip the balance in favor of free radicals, creating “oxidative stress” in the body and brain.

UNT suggested that doctors test for this problem before prescribing testosterone therapy to Caucasian males.

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