Growth Hormone Changed Older Bodies, for Better and Worse

By Gina Kolata

NY Times, November 13, 2002

Over the past few years, hundreds of clinics have sprung up, providing human growth hormone to thousands of elderly people looking for a fountain of youth. Athletes, would-be athletes and bodybuilders also take it, often in huge amounts, hoping to build muscle. But there has been almost no objective evidence on whether it works.

Now, in one of the largest and most careful studies so far of human growth hormone in healthy older people, researchers find that it can markedly transform older people's bodies. The effects were potent. Those who took the drug gained lean body mass, much of which is likely to be muscle, and lost fat as if they had been working out in a gym, lifting weights and doing aerobic exercise. Some men gained 10 pounds of lean body mass and lost an equivalent amount of fat. Yet the subjects, who ranged in age from their mid-60's to their late 80's, were sedentary and did not exercise or change their diets.

But the investigators caution that these gains were accompanied by serious adverse side effects in nearly half the subjects, who developed pre-diabetes or diabetes, aching joints and swollen tissues.

The findings, the scientists said, give them hope, but much work remains. The study lasted just six months, and there is concern that growth hormone may have terrible long-term effects — in animals it can actually speed aging and reduce the life span, and scientists fear it could promote the growth of cancers. In people, growth hormone can cause arthritis, and some experts worry that the joint pains that plagued many in the study might lead to arthritis if the drug were continued.

"This is a fascinating area for further research," said Dr. Marc Blackman, a director of the new study, which is being published today in The Journal of the American Medical Association. But, Dr. Blackman cautioned, "we don't think this is ready for prime time yet."

Growth hormone therapy should not be used outside a controlled clinical trial, said Dr. Blackman, who directs the laboratory of clinical investigation at the National Center for Complementary and Alternative Medicine.

The researchers were asking whether growth hormone and, possibly, sex hormones might be a key to the debilitating changes that occur with aging. Starting about age 30, growth hormone levels start to decline. By age 60, people can have half as much as they did at 30. Testosterone, in men, declines, too, and, in women, estrogen levels plummet after menopause. The hypothesis was that the effects of aging — shriveling muscles, thinning bones, increased body fat, especially in the abdomen, a loss of energy and enthusiasm, might be linked to hormone deficiencies, and, in particular, a lack of growth hormone.

People who lack growth hormone — for example, patients with a genetic defect or a tumor of the pituitary gland that prevents the hormone from being made — have all these signs and symptoms of aging, and they are reversed when they take growth hormone injections.

Sex hormones may also play a role, Dr. Blackman said. "Sex steroids stimulate the growth hormone system," he said. "At least in younger people, when one is awry, the other one goes down."

In their study, the researchers tried to recreate in older people the hormone levels of a 20- or 30-year-old. They recruited 57 women and 74 men, with ages from 65 to 88, giving them hormones or dummy medications.

The most striking results were in the men who took both growth hormone and testosterone. They gained almost 10 pounds of lean body mass and lost a corresponding amount of fat. They also increased their cardiovascular endurance, a measure of their ability to exercise. Men who took growth hormone alone gained seven pounds of lean body mass and lost a similar amount of fat but their endurance did not change.

The women who took growth hormone, with or without estrogen and progesterone, gained a few pounds of lean body mass and lost five pounds of fat. In both men and women, sex hormones alone did not significantly change their body composition. Growth hormone appeared to be the major factor.

The side effects, however, were serious, afflicting 24 percent to 46 percent of the men and women taking growth hormone and including swollen feet and ankles, joint pain and carpal tunnel syndrome, which is caused by a swelling of a tendon sheath over a nerve in the wrist. It, and the joint pain, might be caused by the drug's tendency to increase water retention, Dr. Blackman said.

But Dr. S. Mitchell Harman, an author of the new study and director of the Kronos Longevity Research Institute, a nonprofit center that does research on aging, said it might be a result of growth hormone's effects in increasing tissue growth.

In addition, half the men who took growth hormone also had impaired abilities to use glucose, developing either diabetes or a prediabetic condition. But all these adverse effects disappeared when the study ended and the men and women stopped using the drugs.

Participants in the study did not grow stronger, even though they gained muscle, but it is possible that that might change if the treatment continues longer, said Dr. Harman, who also helped direct the study. Dr. Harman noted that when the hormone was given to people with rare medical conditions who lacked it, "you see very little increase in muscle strength until a year."

Dr. Blackman was cautious. "I personally believe these data are quite exciting," he said. "But there are two issues that are the bottom line. One is that we are uncertain about the possible effects and their functional relevance — getting out of a car, being able to bathe. The other is that there needs to be a lot more research with larger numbers of people and a reduction of these adverse effects."

Dr. Michael Thorner, chairman of the department of medicine at the University of Virginia School of Medicine, said the recent fall from grace of hormone therapy in menopause should give people pause. "If you just advocate that growth hormone be used because it might help," Dr. Thorner said, "the next thing you know, the whole world is on it. I think in medicine one should tailor therapies based on evidence."

The marketing of growth hormone took off in 1990 with the publication of one preliminary study of 12 men, indicating that they had lost fat and gained muscle. Soon afterward, researchers said, anti-aging clinics sprang up to offer the drug, at a cost of $1,000 or more a month, to people looking for a way to turn back the clock.

Growth hormone, made by Genentech, Eli Lilly & Company and others, is approved for use by children and adults with rare medical conditions that make them lack it. But once a drug is on the market, doctors can prescribe it at their discretion.

In just the last four years, according to IMS Health, a company that tracks drug sales, prescriptions for growth hormone made by Genentech and Eli Lilly have more than tripled, rising to 21,000 in 2001 from 6,000 in 1997.

While some prescriptions are for legitimate uses, medical experts say, many others are not. For example, growth hormone is also used by athletes and bodybuilders, with magazines directed toward these groups advertising its availability. The current issue of Men's Fitness, for example, has three ads for growth hormone, providing telephone numbers that people can call for a list of doctors who will prescribe the drug.

"There are plenty of doctors who will prescribe it," said Dr. Harman said. "It's a tremendous scam."