Brain Imaging Study Suggests Long-Term Steroid Use Can Lead to Significant Brain Structural and Functional Abnormalities

June 15, 2015

Results of the first systematic brain imaging study conducted on long-term users of anabolic-androgenic steroids reveal significant brain structural and functional abnormalities, according to doctors at McLean Hospital.

An article detailing their findings, “Brain and Cognition Abnormalities in Long-Term Anabolic-Androgenic Steroid Users,” was published last month in the journal Drug and Alcohol Dependence.

“Anabolic steroids are the newest of the world’s major forms of drug abuse,” said Harrison G. Pope Jr. MD, co-director of the Biological Psychiatry Laboratory at McLean, professor of psychiatry at Harvard Medical School, and co-author of the article. “This is a public health problem that is just coming over the horizon now and we’re only beginning to understand its consequences. Widespread use of steroids did not appear until the 1980s in the United States, so this is a very young form of substance abuse in contrast to other drugs like marijuana and opiates that have been around for thousands of years.”

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According to Dr. Pope, the majority of steroid users are not professional athletes, but rather individuals working out trying to “get big”

And while professional athletes make the headlines for steroid use, he said, that is not where the abuse is rampant.

“Professional athletes account for a tiny fraction of steroid users,” said Pope. “The great majority of steroid users are not competitive athletes at all, but are rank-and-file guys at the gym who just want to get big. This is one of the reasons that the problem has not been widely recognized, because the public has been focused on the occasional high-profile athletes who have been found to take steroids.”

There are approximately three million American men who have used steroids at some time in their lives, he said. From that number, it is estimated that one million have developed steroid dependence where they continue to take steroids for long periods of time, often in spite of the adverse effects, and this number is likely growing.

While studies have been published by Pope and others on the cardiovascular, endocrine, and cognitive effects of long-term steroid use, this is the first time that doctors have been able to systematically examine changes in the brain from long-term steroid use, said Marc J. Kaufman, PhD, director of the Translational Imaging Laboratory at McLean, associate professor of psychiatry at Harvard, and also one of the article’s co-authors.

“We used three types of imaging methods to examine different parts of the brain, including magnetic resonance imaging (MRI), which tells you about brain structure; functional magnetic resonance imaging (fMRI), which measures brain activity by detecting changes in blood oxygenation; and magnetic resonance spectroscopy (MRS), which looks at levels of different chemicals in the brain.”

The study ran from the fall of 2013 to the summer of 2014, using subjects drawn from a pool of 150 male weightlifters ages 35 to 55, with the average age being 42. Brain images of those reporting long-term use of steroids were compared with images from non-users.

One of the key findings with the structural imaging data, said Kaufman, centered on the amygdala, the part of the brain related to emotion regulation, aggression, anxiety, and possibly even depression, which was enlarged in those who were chronic steroid users as compared to the non-users.

“The amygdala in the steroid users wasn’t just a little bit larger than the control group, it was more than 20% larger,” said Kaufman. “That is a really marked difference, and it is particularly interesting because previous studies have shown that amygdala enlargement has been associated with aggression among other types of substance abuse populations.”

The study uncovered another abnormality among steroid users: a decrease in the brain levels of a sugar known as scyllo-inositol, which plays a key role in preventing neurotoxic proteins from clumping, particularly beta-amyloid protein which is known to play a role in the development of Alzheimer’s disease and other dementias.

“Clumping of beta-amyloid protein basically gums up the pipes in cells and leads to early cell death. The levels of this protective scyllo-inositol were significantly lower in steroid users,” said Kaufman.

“If scyllo-inositol depletion is a widespread phenomenon among steroid users,” he said, “we could be seeing more cases of dementia or Alzheimer’s in these men as they age.”

Said Pope, “Another reason for concern is that unlike alcohol and most illicit drugs, which leave your body fairly quickly after use, steroids can be present in the system at levels 20 to 40 times greater than natural testosterone levels, 24 hours a day, seven days a week, for the entire duration of a course, or so-called ‘cycle,’ of steroid use.”

“The body can never be rid of them because users are typically injecting long-acting steroids regularly throughout their cycle,” he said. “As a result, there’s never a break. The body has no moment to rest from the effects. That is quite different from most drugs that are abused. And that’s why we worry that steroids might have unique forms of toxicity that we don’t typically see with other drugs of abuse.”

Pope also pointed out that steroids are not addictive in the sense that alcohol or drugs are addictive, but users develop a different type of dependence syndrome. He gave three reasons for steroid dependency:

  • Body image: Weightlifters get big and they become fixated on wanting to stay that way. This fixation develops in much the same way that women with anorexia nervosa can weigh 87 pounds and look in the mirror and still think that they look fat. In steroid users, the pattern is simply the reverse; they may weigh 230 pounds with a 32-inch waist and still think that they are not muscular enough.
  • Endocrine effects: When a male takes steroids, which are all synthetic derivatives of testosterone, the body subsequently shuts down its own production of testosterone. If that person then stops using steroids, his own testosterone production may take weeks, months, or occasionally years to return to normal. He may develop impaired erectile function, loss of sex drive, and sometimes depression when coming off steroids, which often motivates him to go back to using the drugs.
  • Hedonic effects: There’s a pleasure experience that is associated with taking steroids. It’s not the same as getting high as with drugs or alcohol, but there is a reinforcing quality of some type. Some steroid users describe this as feeling self-confident or invincible. Scientists are convinced of this phenomenon because male hamsters in laboratory studies will self-inject steroids to the point of death if they are given the opportunity.

When trying to get off of steroids, the user has to be given medications to try and stimulate his own testosterone function while slowly tapering the external steroids, Pope said. “It’s an elaborate program that requires an expert endocrinologist and sometimes also a psychiatrist, so it’s a difficult process.”

Kaufman pointed out that while the findings of the study are alarming, they are preliminary. “The results merit an extended, more comprehensive sample in order to build a strong scientific foundation,” he said. “We are applying for funding to conduct a larger study. These results need to be followed up because they have many implications. For example, clinical trials are already underway to establish whether replacement of scyllo-inositol can be useful for preventing cognitive decline in people with early Alzheimer’s, an approach that may prove useful in steroid users.”

In any case, said Pope, “It is urgent to pursue this area of research, given the potential implications for the millions of men who have used or who are contemplating using steroids.”

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