San Francisco Chronicle - December 27, 2004
Carl T. Hall at chall@sfchronicle.com.

Despite the well-documented risks of side effects from high doses of muscle-building hormones, doctors insist the drugs have legitimate uses -- and genuine benefits for athletes when used wisely.

Nobody defends cheaters.

At the same time, many doctors and pharmaceutical experts say it's important not to rush to judgment about the chemical agents some of the cheaters appear to be using, particularly testosterone and related hormones in the class of drugs known generally as anabolic-androgenic steroids.

Hormones are the messengers of the body, produced in the various glands of the endocrine system to regulate metabolism throughout the body. They are by nature potent molecules that may affect virtually every organ system one way or another. Testosterone, the main male hormone, is one of the main drivers of muscle growth, and has profound effects on mood and sexual function. Many of the steroids in use are synthetic relatives of the natural molecule, reshaped to get different effects -- or to thwart testing methods.

Medical specialists warn that illicit use of powerful hormone supplements is asking for trouble. But the idea that these drugs "are equivalent to taking heroin or something is very unfair," said Dr. John Baxter, a professor in the metabolic research unit at UC San Francisco and a former president of the Endocrine Society, a medical group for hormone specialists.

Baxter did some of the fundamental genetic work that led to the cloning of human growth hormone, which led to commercial production of a synthetic version -- and yet another chemical enhancer popular in some bodybuilding circles. Now, he fears the spate of publicity about illegal doping in sports may be obscuring the legitimate value of hormone replacement.

"The thing that disturbs me is that we seem to be demonizing something that for many people could have great therapeutic benefit," he said.

Baxter made it clear that he had in mind aging men with declining testosterone levels, not healthy athletes in the peak of their careers, and certainly not youngsters.

"There are problems with these drugs," he said. "But in older men, with lower levels of testosterone, replacement therapy with this class of hormones is probably going to be beneficial."

Testosterone and its brethren hormones are among the most closely studied molecules in medicine, and yet mysteries remain about their precise mode of action and many -- sometimes contrary -- effects. They work in unpredictable ways that vary from one person to the next, depending on how the hormone finds its way to their particular receptors.

These hormonal docking sites are scattered throughout the body. The precise structure and location of the receptors determine the hormone's effect. Dosages and duration of use are among the critical factors complicating the puzzle. Receptors can become saturated after chronic use, requiring higher doses to achieve the same result.

Chronic heavy use can disrupt the body's natural hormone production and regulatory system. Men can become feminized, women masculinized. In children and teenagers, some performance-boosters can stunt growth.

Because of the potency of the hormones, our bodies contain feedback loops to curtail production when their levels get too high. That is why hormone supplements can have paradoxical effects, sometimes persisting long after the drug use is stopped.

"It shrinks the person's own glands," said Dr. Adrian Dobs, an endocrinologist at Johns Hopkins University School of Medicine.

But doctors no longer bother to argue, as they once did, against anecdotal reports from athletes claiming that hormone supplements help pack on muscle and boost strength. Studies show the drugs really do help add lean muscle when used along with a high-protein diet and vigorous training.

Human growth hormone, produced in the pituitary, is the main growth regulator in children and has important metabolic effects in adulthood. Injections are used to treat muscle-wasting in AIDS -- and may help athletes bulk up.

"If you take exogenous human growth hormone to get big muscles, it doesn't necessarily mean those muscles are going to be stronger," said Dr. Gary Wadler, a New York University professor and one of the nation's leading experts on steroids in sports. "But if you take the combination of human growth hormone to make (the muscles) bigger, and then add to the mix a polypharmacy of anabolic steroids, then you can take those bigger muscles and make them stronger.'' Side effects may be part of the bargain, but "you can get the desired effects for a while," said Dr. William Roberts, who is part of the family medicine department at the University of Minnesota medical school and president of the American College of Sports Medicine.

He even tried a rub-on steroid cream on his own torn leg muscle after a skiing accident, hoping to recover in time for a long-planned family vacation.

"They told me it would take six months to be skiing again, and I had a vacation scheduled in six weeks. So I used it locally, and in fact I was skiing in six weeks. I thought it was worth a try, but to me, that's different than using it to improve my contract with the Yankees, or even to improve my skiing," he said.

Part of the way the drugs work is by promoting faster muscle healing. That's important even without an injury; athletic training is all about breaking down and rebuilding muscle tissue.

"When you are training hard, there is probably going to be some muscle damage, and if that damage is repaired more quickly, it means you can get back to hard training faster," Roberts said. "There may be applications for that in older guys like me who tear easy."

Doctors said it's hard enough to track the effects of steroids prescribed to their own patients, let alone predict the long-term impact of illegal drug use in sports. Dr. Marc Safran, head of sports medicine at UCSF, said side effects are inevitable from underground use.

He treats some of those who have suffered these effects, including one former steroid user now on long-term testosterone replacement to preserve his male body traits, having burned out his own hormone production system.

Although such risks are well- known, Safran said it's impossible to quantify how serious the dangers might be.

"Because they are banned substances in sports, and because they are dangerous substances that can cause irreversible harm, it's not ethical to do true scientific studies of these medications as they actually are being used," Safran said. "So we are kind of stuck on the anecdotal experiences as far as what's going on with illicit use."

Evidence suggests widespread use in all levels of sport.

At World Gym in San Francsco, general manager Rory Kurtz insisted that drug use is not tolerated. He also said prohibitions are widely ignored -- because the drugs obviously give bodybuilders the desired results. "So many people are on stuff these days, it's kind of one of those things," he said. "I can point to people and can just tell by looking at them. Even some smaller guys you might not suspect, but you can tell. You'd be amazed how many people take stuff."

Wadler said this sets the stage for "a big-time public health issue" in the future as the inevitable downside becomes clear, citing such risks as weak bones and elevated fracture risks as the former muscle-builders get old.

"There's something very unique about hormones," he said. "The adverse effects don't manifest themselves for months, years or even decades."

FEEDBACK LOOP

Balancing normal testosterone production and pituitary gland function

-- Pituitary hormones help regulate testosterone and sperm production

-- Natural testosterone controls hormone secretion.

Steroids disrupt feedback loop

Elevated hormone levels shut down natural glandular activity. Men may suffer shrinkage of the testicles, reduced sperm count and enlarged breasts. Women may experience masculinizing effects. .

HOW STEROIDS WORK 1. Blood carries steroid to muscle 2. Steroid is drawn toward muscle cellÆs wall and attaches to a receptor 3. Steroid enters cell nucleus, interacts with chromosomes 4. Nucleus sends out information to increase protein production, which strengthens and increases muscle.

STEROIDS HEALTH RISKS

Heart disease: Increased levels of bad cholesterol

Liver damage: Oral steroids may be particularly difficult for the liver to metabolize

Tendon ruptures: Steroids can make muscles bigger and heavier, but not tendons, creating risk of rupture during exercise

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