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The Steroid Story

POSTED 16 DEC 2004

No question
Anabolic steroids are powerful meds. They don't just grow muscles: Users get a high, a feeling of energy, enthusiasm and power.

But are they harmful? That's a broad question. For one thing, about 100 compounds mimic the effects of testosterone, and each could have different effects. And hormones affect the cardiovascular and reproductive systems, the liver and the brain.

Jubilant, muscular woman runs with outstretched arms.Marion Jones celebrates while winning the 100-meter sprint at the 2000 Olympics. Did those muscular arms benefit from illegal testosterone? In 2000, she was married to shot-putter C.J. Hunter, who tested positive four times for steroids at the Olympics. Chief BALCO store-minder Victor Conte has said he watched Jones use human growth hormone, another banned substance. Jones has never failed a drug test and denies the accusations.
AP Photo/CP, Kevin Frayer

Let's narrow the question to a digestible chunk: Does taking steroids increase aggression? Even that question is resistant to easy answer.

In a rare, controlled study of the effect of anabolic steroids on human psychology, Harrison Pope of Harvard Medical School found a significant increase in aggression -- but the results were uneven: "Most participants showed little change and a few showed marked changes" (see "Effects of Supraphysiologic..." in the bibliography.)

A second approach is to study animals, even though we realize that people -- most, anyway -- are not rodents. Richard Melloni, associate professor of psychology at Northeastern University, sees a strong link between steroids and aggression. Since 1995, he has been dosing adolescent hamsters with testosterone variants and watching changes in three brain chemicals: the neurotransmitter GABA, vasopressin and serotonin. The first two increase hamster aggression, while serotonin reduces it.

Steroids increase aggression in adolescent hamsters and rats. What do they do to human adults?The same effects seem to hold for people, Melloni says. In a series of tests, Melloni's research group gave adolescent hamsters a steroid cocktail in concentrations that mimic how athletes take 'roids. The drugs caused a two-to-four-fold increase in the activity of vasopressin, a molecule that constricts blood vessels and triggers aggressive behavior in hamsters. "It's a dramatic increase," says Melloni.

The vasopressin change focused on the hypothalamus and the amygdala, brain structures concerned with aggression and emotion. Having seen steroids change GABA in the same way, Melloni concludes that "steroids activate at least two systems related to aggression."

After the shot
What's important, Melloni says, is that the changes were occurring during a time when the hamster's brain is normally being shaped by the hormones of adolescence (parents: Sound familiar?). Extra hormones affect how the brain gets wired, and that changes behavior, Melloni says.

The aggression tapers off after three months, in a pattern that confirms the relationship between vasopression and aggression. Because both behavior and vasopressin activity return to normal at about the same time, Melloni says, "We think this is a causal effect. The steroids have changed the system, made an individual aggressive, it's fascinating."

While steroids raised GABA and vasopressin, they reduced the level of serotonin, a neurotransmitter that suppresses hamster aggression, and that deficit does not disappear. That change may shed light on the depression that may accompany steroid withdrawal. "The serotonin system never recovers, it's always depressed," says Melloni. "Low serotonin is implicated in high rates of depression, and this may be why a high number of high-dose steroid users develop depression on withdrawal."

tabs in foil package Overall, says Melloni, steroids are a very dangerous drug. "They have dramatic effects on the brain, heart, and liver biology, bone density... and we are in our infancy in our trek to understand how dangerous these things really are."

Rats on 'roids
Marilyn McGinnis, a research professor in the department of biology at the University of Texas at San Antonio, also injects animals with steroids. But instead of peering inside their itty, bitty, brains, she focuses on behavior -- of rats instead of hamsters. When adult and adolescent animals get testosterone, she says, "there is an increase in aggression." But stanozolol, another anabolic steroid, "inhibits aggressive and sexual behavior, but is high in anabolic properties."

In an effort to understand rat 'roid rage, McGinnis and colleagues tested how the rodents responded to social cues that normally spark aggression. A male rat is usually aggressive toward males that intrude on their territory -- unless the intruder has been castrated.  Steroid-treated rats could "distinguish appropriate cues" in the situation, McGinnis says.

In a different situation, however, the rat-fellas went ape. When the researchers startled them by pinching their rat-tails, "that dramatically increased aggression in testosterone-treated males," McGinnis says. This wasn¹t just a normal reaction to the pinch. Oddly, she adds, the guys "show exactly the same response if you tailpinch the opponent, suggesting that a high level of anabolic steroid is lowering the threshold to respond to a perceived threatening stimulus, even if they don¹t feel it, or if it's not really threatening to them." 

The studies show, she says, that "Adolescence is a critical period during which they help form the neural circuits that are responsible for mediating reproductive and aggressive behavior. Anabolic steroids help mature those circuits, so the presence of chronic high levels during puberty may have a very different effect than duringadulthood." In other words, while the changes in adult rats may be temporary, the changes in adolescent rats may be permanent.

The real fear is that young people are taking steroids. They can have prolonged, possibly permanents effects on the brain.

Confound it!
While Melloni strongly cautions against the aggressive effects of steroids, McGinnis is more equivocal. "I think if you are a normal adult, and take steroids for a little while, it will probably not have any harmful effect, but there are people out there who perhaps are more prone to psychiatric problems, and anabolic steroids would tend to exacerbate them." For kids it's a different story. "I think the real fear is that young people are taking them, and I do think they can have prolonged, possibly permanents effects on the brain and reproductive functioning."

We asked Peter Hoaken of the University of Western Ontario to sum up the impact of steroids on human aggression. He helped review the effect of illicit drugs on aggression (see "Drugs of Abuse..." in the bibliography), and told us the answer would be complex. "You need to differentiate intoxication from withdrawal from neurotoxic effects. If you run into somebody in a bar who is drunk, they maybe become aggressive. If they have smoked pot for a very long period and abruptly terminated it, they may become aggressive. If they took MMDA and damaged the serotonin pathways in the prefrontal cortex, that may make them more aggressive."

Colorful assortment of pills, tablets and capsules.What role should these guys play in sports? Photo: NIH

Most studies of human aggression and steroids asked athlete-users to describe their behavior on the drugs. "Researchers have found, essentially, a much greater incidence of aggressive interactions among those who have taken steroids," Hoaken says. "But the kind of people who tend to take androgenic or anabolic steroids are young men who are hypercompetitive, and take steroids to get bigger, stronger, or faster, so they are more likely to succeed in their chosen athletic endeavors." So these athletes might naturally be more aggressive than average.

A second difficulty is relying on memory, which typically causes errors in "retrospective" studies. Finally, Hoaken points out, we must consider the familiar drug alcohol. "The drug that undoubtedly causes the greatest increase in aggression is alcohol.... Young athletes binge drink at an alarming frequency," and that may explain higher rates of aggression among these athletes.

So does taking steroids make you more aggressive? Maybe yes, and maybe no, says Hoaken. "You can't make any causal commentary, because it's very difficult to do controlled studies." After looking over past studies, he says, "There's not a heck of a lot there. Most studies are retrospective, and I think they are hopelessly confounded."

Should we clamp down harder on steroids?

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Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

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