Richard Sprott, left, and Richard Hodes of the National Institute on Aging. (Photo/Michael Lutzky for The Post) In This Report Side Effects of DHEA Researching Testosterone Growth Hormone Debate Melatonin's "Dark" Mystery

By Susan Okie
Tuesday, Feb. 24, 1998; Page Z12

Elmer M. Cranton is putting his trust in hormones. Like plenty of other 65-year-olds, he doesn't look forward to old age -- but as a physician, he has decided to fight back. He says he has read most of the medical literature on growth hormone, DHEA, melatonin and a handful of other hormones -- chemical messengers naturally produced by the body -- that have recently been promoted as "anti-aging" treatments.

"I was impressed by it -- impressed that it was safe, impressed that it would do some good to slow the aging process," he said. So, about five years ago, Cranton began taking low doses of growth hormone, an expensive prescription drug that must be injected several times a week. Since then, he's added four additional hormones to his regimen: DHEA, melatonin, testosterone and pregnenolone.

Many scientists studying these hormones say it's far too early to conclude that they're safe and effective when taken for long periods by healthy elderly people. But that hasn't stopped Cranton, a Harvard-trained family practitioner who works in Yelm, Wash. He says that he and the several dozen patients to whom he prescribes low doses of hormones in various combinations are too old to wait for research to provide a definite answer.

"I don't want to get old," he said. "I encourage people to measure all these hormones [in their bodies] and replace them all" to the levels that are normally found in people in their thirties or forties. "Like an orchestra, they all work synergistically, one with the other."

Many ongoing studies are focusing on whether supplementing certain hormones can prevent or ameliorate the unwanted effects of age -- effects such as increased body fat, muscle wasting, thinning and wrinkling of skin, bone loss, sleep disturbances, undesirable changes in cholesterol and other circulating fats, reduced sex drive and weakening of the immune system. At universities and medical centers around the United States, scientists are testing hormones -- alone, in combination, and in conjunction with exercise regimens -- in more than 25 studies funded by the National Institutes of Health. Similar studies are taking place in other countries.

"The biology of these hormones, and some of the experimental evidence . . . suggest there may be useful applications. Further research is justified," said Richard J. Hodes, director of the National Institute on Aging.

Emerging Clues

For estrogen, the best studied hormone, more than two decades of research have already established some clear benefits of hormone "replacement therapy." In large studies, this female sex hormone has been found to reduce women's risk of heart disease -- the number one killer of American women -- by between 33 percent and 46 percent, leading to a lower overall death rate in estrogen users. It also confers about a 15 percent reduction in the risk of hip fractures caused by bone loss, a slight reduction in the risk of colon cancer, and even some apparent protection from Alzheimer's disease.

The research has also identified some clear risks. Taken alone, estrogen causes higher rates of cancer of the lining of the uterus (the endometrium), but taking it with progesterone, another female sex hormone, greatly reduces this risk. Estrogen also produces an increase in breast cancer risk that becomes apparent when a woman has been on the hormone for about five years; the risk grows larger with continued use. Estrogen also somewhat raises a woman's risk of gallstones and of blood clots in leg veins.

For other hormones, the benefits and dangers aren't nearly so well defined. Researchers studying their effects on aging say that some of the early findings are promising, but none has been proven to thwart the aging process and they caution consumers against trying out multiple-hormone combinations outside of scientific trials.

"There's an exciting, emerging information base. . . . [It's] compelling to think that there may be some utility to all this," said Marc R. Blackman, a professor of medicine at Johns Hopkins University School of Medicine who is conducting a trial of supplementation with growth hormone and sex hormones (estrogen/progesterone or testosterone) in elderly people. "It's just that we're not there to say that yet. We're sort of knocking on the door."

Scientific interest in possible anti-aging effects is most intense in the case of growth hormone, but experts in the field are quick to point out that their level of understanding of that hormone's long-term effects in older people is comparable to the state of knowledge about estrogen replacement 20 years ago.

"No real clinical data are available to support the concept that you can use it as a fountain of youth or for prevention of aging," said Steven W.J. Lamberts, a professor of medicine at Erasmus University in the Netherlands. Except for children or adults with clear-cut growth hormone deficiency, he added, "there should really be no use whatsoever -- especially in old age."

Several other hormones -- DHEA, the male sex hormone testosterone and melatonin, for example -- have been touted in books and in the media for their supposed anti-aging effects, including improvements in longevity, strength, sexual potency, and well-being. Scientists say there is inadequate research data from human studies to back up these claims. Many are based on data from animal studies, or on findings from short-term studies in people that have not been confirmed.

Researchers do know that melatonin can help to prevent jet lag in travelers, and they are studying its usefulness for certain sleep disorders in the elderly. The hormone is scheduled to be tested as a sleep aid in astronauts on board the space shuttle this April and again in October, when former astronaut John Glenn is expected to return to space at the age of 77. But there is no scientific evidence that melatonin has anti-aging properties in humans.

Several NIH-funded studies are evaluating testosterone's effects on muscle mass, strength, heart function, libido and other factors in older men, as well as monitoring its potential for promoting prostate cancer. Fewer studies have been undertaken in humans to test the therapeutic potential of DHEA, a steroid hormone that poses problems as an anti-aging treatment because it is partially converted by the body into testosterone, causing frequent, undesirable side effects in women and perhaps promoting prostate growth and cancer in men.

For consumers trying to assess the medical claims being made for hormones, the picture may seem confusing. News magazines have run stories on the anti-aging treatments featuring photos of stunning young models -- sometimes male, sometimes female -- as well as headlines about staying "forever young." The implication is that the treatments don't just slow the clock, but make it run backward.

The message from the medical establishment may also sound mixed. For instance, some medical experts complain that an exaggerated fear of breast cancer has prevented many women from availing themselves of the proven health benefits conferred by hormone-replacement therapy with estrogen and progesterone. At the same time, researchers continue to caution the public against trying other hormones, often because of concerns that they may elevate cancer risk.

Varying Federal Regulations

Because hormones fall under various laws, they are handled inconsistently by the federal government. Growth hormone, estrogen, progesterone and testosterone are prescription drugs, strictly regulated by the Food and Drug Administration. But melatonin and DHEA, although they too are hormones, are sold as dietary supplements and can be purchased and used without medical supervision. And a variety of other dietary supplements are being promoted in the media and on the Internet that claim to provide "natural" hormones -- often from plant sources -- or to boost the body's own production of these powerful chemical messengers.

The rationale behind using any of these hormones as anti-aging treatments is simple -- perhaps too simple, says Richard L. Sprott, the associate director of the National Institute on Aging (NIA). "They all are hormones that decline with advancing age," he said. "The assumption [is] that if you see it going down, it must be bad. If you could put it back, you would restore youthful function and that would be good."

The problem, Sprott said, is that "these last two assumptions are often not true. They're dangerous assumptions to make."

For now, most medical authorities advise that, except for estrogen and progesterone in post-menopausal women, hormones should be "replaced" only after a patient has been tested and found to be deficient in a specific substance. Most elderly people have lower levels of growth hormone and sex hormones than young adults, so deficiency is defined as a level that is abnormally low for the patient's age, or as a level that doesn't change appropriately in response to measures that should stimulate increased production of the hormone in a healthy person.

Sprott noted that hormones sold as dietary supplements usually carry a disclaimer that warns people not to take them without a doctor's advice.

"I think that's a little disingenuous," he said. "How many people are going to go out and get a $400 doctor's appointment that tells them what their levels of DHEA and melatonin are?"

Hormone therapy is only the latest weapon in humankind's long campaign to defeat aging. That dream has preoccupied scientists, writers and consumers for centuries -- and entrepreneurs have been exploiting the dream for almost as long.

But Sprott said that for people now facing old age, the search for a way to preserve well-being may be growing more desperate because life expectancy has increased in many countries without a corresponding improvement in the quality of life for elderly people.

"If we [increase life expectancy] and at the same time we don't affect the time of onset of debility and disease, we are going to dramatically increase human misery, not decrease it," he said.

These days, doctors who call themselves specialists in "anti-aging medicine" advertise hormone treatments on the Internet, although anti-aging medicine is not a specialty recognized by any established medical organization.

"I can measure your hormone levels and reverse the negative trends of aging with hormone replacement, vitamins and nutritional supplements," says a statement on the home page of one such practitioner, William S. King of San Diego.

King, a former emergency physician, said in an interview that he is phasing out his private practice in favor of marketing a line of products, consulting and speaking to groups. "It's too hard to educate patients one by one," he said.

Another physician, Ronald Klatz, declares in a 1995 book, "Aging not only can be arrested but can actually be reversed." In his book, "Grow Young With HGH [Human Growth Hormone]," Klatz urges elderly people to buy various dietary supplements that he claims will make their pituitary glands manufacture more of the hormone or, if that fails, to seek out a doctor who will prescribe growth hormone supplementation.

Blackman of Johns Hopkins said while some studies in animals indicate that large doses of certain protein constituents, such as the amino acids arginine and lysine, can sometimes increase growth hormone levels, the science doesn't support the claims being made for dietary supplements as growth hormone boosters.

"It doesn't work the way it's being touted," he said. "This is an example of taking a small amount of science and metastasizing [spreading] untruths."

Cranton too has written a book, "Resetting the Clock," on using hormones to try to slow the effects of aging. He said the ones he prescribes most often are DHEA, estrogen-progesterone replacement for women, and testosterone for men. He said only a few of his elderly patients can afford growth hormone treatment, which isn't covered by insurance and costs an average of $5,000 to $6,000 per year at the doses he usually prescribes.

Cranton said he believes the hormones he takes have improved his overall health.

"In the last two years . . . I lost two inches around my waist, but I did not lose weight," he said. "It went from fat into lean body mass. My endurance is better. My energy level is higher. It's a long time since I've had any cold, flu or viral infection. I think my memory and my mental alertness has improved."

"I don't know if I can attribute that all to growth hormone" or to the other hormones, he added. "It's a spectrum of subtle things."

He said he's willing to accept the possibility of some increase in cancer risk, which he acknowledges may be a side effect of boosting his levels of growth hormone and testosterone back to what would be the normal range for a man in his thirties or forties.

Multi-hormone regimens such as Cranton's are not endorsed by the medical community. For estrogen and progesterone treatment in post-menopausal women, researchers say, strong scientific evidence supports the reasonableness of the kind of trade-off he describes. But for other hormones, such as growth hormone, DHEA or testosterone, the science isn't there, and people who try to stave off aging with such substances are taking a chance.

"He may be right," said S. Mitchell Harman, acting clinical director of the National Institute on Aging, referring to Cranton's point of view. "But we haven't quantified it yet."

Resources

For more information on hormone supplementation and on other aging-related topics, call the National Institute on Aging's toll-free number, 800-222-2225, between 8:30 a.m. and 5:00 p.m. EST, Monday through Friday. Information is also available at the institute's web site .