Hooked on youth

THE LATEST ANTI-AGING DRUG IS CHEAP, CONVENIENT, AND MAKES YOU FEEL LIKE A KID AGAIN. SO WHY AREN'T WE ALL TAKING IT?

MARIA BOWMAN SUSPECTED the golden years were reserved for people in lemonade commercials, those white-haired beauties who live in a world of soft sunlight and front porches. You don't suddenly wake up one morning as Joanne Woodward, smart in tennis whites for summer on the Cape, cozy in cashmere for winters in Aspen. If only healthy skepticism guaranteed a healthy lust for life. Maybe then the woman in the mirror wouldn't have looked over 50 years old, still Maria, still proud and pretty, but now visibly exhausted by a day's work and unable to summon the breath for much else.

"I know how people grow old in this country," she says. "They sit. They sit there in retirement homes. It's a terrible waste. I don't have to live to be a hundred but, my God, I want to be alive. I want the energy to take care of myself, to work if I want, and to pursue new projects."

For much of 1994, Maria Bowman had just that life. As part of an anti-aging study at the University of California at San Diego, she dosed herself daily with capsules of dehydroepiandrosterone, or DHEA, a hormone naturally secreted by the adrenal glands. For six months she not only had the energy to put her house and garden in order and sell property in a flat real estate market, but she found the time to take up golf, sharpen her tennis game, and read more. Her suburban San Diego house is filled with Asian artwork, golf magazines, a practice putting green, collections of poetry, a copy of Dostoyevsky's Notes From the Underground--the paraphernalia of an active, curious mind.

In truth, Bowman wasn't told when she was taking DHEA. Like the study's other 15 participants, all over age 50, she took the hormone for half the year and a dummy pill for the other half, never knowing when she was taking which. "My body knew," she says. "I slept less but I slept better. I felt eager to get out of bed in the morning. And there's no question I felt more feminine, more sensuous. I sure did notice the difference."

So did most of the others. According to reproductive endocrinologist Samuel Yen, the study's principal investigator, DHEA increased muscle mass in both men and women, and the men gained strength and lost fat. But the most noticeable effect was the way the drug made people feel: In a previous study of 30 middle-aged people, Yen found that 82 percent of women and 67 percent of men scored higher on a series of tests measuring their ability to handle stress, their quality of sleep, and overall well-being when they were on DHEA. Less than 10 percent reported feeling better while on a placebo.

"This is not a fountain of youth. It is not going to make you live longer," said Yen, trying to temper the mounting excitement after announcing his most recent results at the first conference on DHEA and aging, held in Washington, D.C., last June. "It is a drug that may help people age gracefully." That Yen is approaching 70 and took the hormone himself didn't exactly cool the air; CBS's "Eye to Eye" rhap-sodized at length.

Unfortunately for Maria Bowman, her DHEA supply ran out the day Yen's study concluded. She'd love a refill, except that the Food and Drug Administration halted over-the-counter sales in 1984 because the hormone had no proven benefits and its long-term effects are unknown. A supplement made from wild Mexican yams that claims to be a "precursor" to DHEA is available in some health food stores and through ads on the Internet. But researchers say the body doesn't convert the stuff to DHEA. The drug is available, however, because of a loophole in FDA regulations that allows pharmacies to mix up any drug for patients with a prescription. And prescriptions for DHEA are getting easier to come by. Scores of maverick doctors across the country are doling them out to patients with everything from flagging libido and joint pain to early Alzheimer's disease and cancer.

No one knows how many people are receiving the hormone this way, but doctors at the DHEA conference put the number in the thousands. As word of mouth grows, business is bound to get brisker. Just compare DHeA to human growth hormone, the last anti-aging drug to attract this much attention. Whereas HGH has to be injected twice a day, taking DHEA is as easy as popping a pill. And while a month's supply of HGH costs about $800, pharmacies sell a month's supply of 100-milligram capsules of DHEA for as little as $30.

"There's a big underground for this," says Kenneth Gorelick, chief medical officer of Genelabs Technologies Inc., a Redwood City, California, company that is testing DHEA for use against lupus, a disease that seems to cause shortages of the hormone. "And it appears to be growing."

So Maria Bowman faces a decision, one that millions of us will encounter in decades to come: Am I willing to be a guinea pig for a promising but unproven anti-aging drug? After a trip to Tijuana in an unsuccessful search for a pharmacy that sells DHEA over the counter, Bowman's getting edgy. "I keep thinking about what it was like," she says. "Maybe I'll try this doctor in Palm Springs."

THE PALM SPRINGS doctor is Edmund Chein, a good-natured, almost jolly, proponent of youth preservation by pill, injection, lozenge--any means available. Chein worked for ten years in Los Angeles as a physiatrist--a medical doctor specializing in physical rehabilitation-before moving to Palm Springs and founding the Palm Springs Life Extension Institute in early 1994. His small office is two blocks from the airport on Taquitz Canyon Way, a silent and pristine boulevard except for shucks of palm-tree bark sprawled under the sun.

"All I have to do is show people the research," says Chein, who has built his practice through radio interviews and ads in magazines, "and they see right away why they should be taking it."

What doctors know about DHEA's effects on the body could practically fit on the back of an envelope. Concentrations of the hormone peak during the mid-twenties. By around age 30 levels begin to taper off until, by 80, most people have less than one-fifth the DHEA they had in their youth. Why would the body produce such an abundance of a hormone and then suddenly tighten the spigot? No one knows. But researchers suspect the decline may be part of the reason we succumb to diseases like heart disease and cancer as we get older. Indeed, blood levels of DHEA--which vary from person to person but average between 300 and 500 micrograms per deciliter in 20-year-olds--may be the most reliable single measure of how quickly our bodies are aging. The fact that some people lose less DHEA than others may explain why some seem to age better than others.

In a 1986 study published in The New England Journal of Medicine, for example, researchers at UC San Diego measured DHEA levels in 242 men 50 to 79 years old, then tracked their health for 12 years. Men whose initial levels were higher than 140 mcg were less than half as likely to have died of heart disease by the end of the study, even when researchers took into account such factors as smoking and cholesterol levels. Those with the highest levels fared the best: For every 100-point increase, there was a 48 percent drop in heart disease risk and a 36 percent decrease in death by any cause.

In animals the hormone seems to act like a magic nectar. Mice prone to obesity stay slim and lean--and live longer-when given daily doses of DHEA. Rodents bred to have a high risk of breast cancer have a much lower incidence of that disease when receiving DHEA. And put older mice on a regular DHEA regimen and their cells attack infectious agents as furiously as do cells from young mice. Old mice on DHEA even look young, their thick, shiny coats and energy making them hard to distinguish from animals half their age.

"DHEA is one of the most abundant hormones in humans, so it stands to reason that it has some biological effects on us," says John Nestler, an endocrinologist at the Medical College of Virginia, who has been compiling evidence showing that a shortage of DHEA contributes to the plaque that builds up in the arteries of otherwise healthy elderly people. "If I had to guess which of those effects were the strongest, I would say protection against heart disease and boosting immunity."

The French endocrinologist Etienne-Emile Baulieu, inventor of the abortion pill RU 486, is wagering that doses of DHEA will sharpen the mind even as they protect the body. The hormone helps brain cells grow in the lab, seems to improve rodents' short-term memory, and has even shown some effect in humans. "We've already seen some correlation between DHEA levels and mental acuity in older people," says Baulieu.

For his part, Chein is hedging all bets. He offers patients not only DHEA but a combination of other hormones, including testosterone for men; estrogen for women; melatonin, a sleep regulator; and human growth hormone--all of which decline with age.

Hormone replacement therapy, as Chein practices it, goes back at least to the late 1960s, when the late Russian gerontologist Vladimir Dilman began writing about what he called the Health Passport. If important hormones such as DHEA and HGH taper off as wrinkles and gray hairs proliferate, Dilman argued, then maybe this hormonal slide is biological aging, in some fundamental sense. So why not keep the tanks full, give the body a passport to youth?

"The idea is simple," says William Regelson, a medical oncologist at Virginia Commonwealth University's medical college and author of the bestseller The Melatonin Miracle. "If you want to maintain a youthful level of health, then you have to be youthful physiologically. You have to maintain youthful levels of these hormones."

AT 66, BOB JONES looks like a country club senior tennis pro, one of those tanned, good-looking types who have been blessed with smart investment advice and a life of leisure. The notion that he spent ten years limp with chronic fatigue--and almost broke--seems preposterous. "It's true," says Jones, a retired marketing executive. "You should have seen me just a year and a half ago. People were always telling me how tired I looked. I mean, I was ready for trade-in."

That's when Jones first saw Edmund Chein. The doctor himself is a sight to behold: an L.A. character from his gold-rimmed glasses down to his white cowboy boots, Chein has the smooth-skinned countenance of an oversized boy, even at 45. Give him a backpack and a Lollapalooza T-shirt and he'd pass for a medical student. Chein won Jones over with his enthusiasm for hormone replacement--and some articles from The New England Journal of Medicine.

"I knew this was a good journal," says Jones. "They don't publish just anything. So I decided to get on the program."

For $250, Chein took Jones's medical history and gave him a physical. It cost Jones another $300 to have his blood measured for various hormones. Using those test results, Chein wrote a prescription for both DHEA and HGH at concentrations Jones's body hadn't seen in about 45 years. "I try to restore the hormone to levels the person had at their physical peak," he says, "which is about age 20 or so."

Chein requires that his patients stick to a daily regimen--"as regular as prayer," he says. And he checks their blood levels of the hormones--every month for the first three months, more sporadically after that--to make sure the replacement dosage is right. In high doses, HGH can cause carpal tunnel syndrome, as well as a diabetes-like affliction in which blood sugar levels become hard to control, leading to dizziness in the short term and organ damage over time.

So far, DHEA hasn't shown such side effects. But because the body uses the hormone to make testosterone and estrogen, the side effects and risks of those hormones may hold for DHEA as well. Testosterone in high doses, for example, can cause facial hair growth, oily skin, and acne in women. It may also possibly increase the risk of heart disease, as well as prostate cancer in men. "If there's any problem at all," says Chein, "I adjust the dose, downward."

Chein will no longer reveal how many patients he has seen-"People have used that number to make me look like I'm running a mill here," he says--but he's a busy man. "It's almost all word of mouth," he says. "I get people from all over the country. Executives, money managers, people in the entertainment business. Two people you see every day when you turn on the TV are my patients. These are all very intelligent, successful people."

In regular surveys Chein asks his patients about everything from skin texture and elasticity to healing of injuries, flexibility, sexual potency, and attitude toward life. Most include comments like, "I've never felt this good" and "I can't believe how much weight I've lost." Chein insists that these subjective comments represent significant changes. Any loss of fat or increase in muscle, any lightening of mood or burst of energy could add up to fewer falls and broken bones, more independence, and less of the clinging depression that can accompany aging.

Certainly Bob Jones agrees. "I feel as good as I have in 20 years." Jones now regularly works out on a home fitness machine and hikes Mount San Jacinto, the towering wall of pale-brown granite that fills the horizon west of town. And he has even renewed his interest in computers, something he swore off after decades in the business. "So much has changed in computers that I have to learn everything all over. But I'm like a kid again on this stuff," he says. "I just feel lucky to have learned about hormone replacement. I think it's the leading edge of what people can do for themselves."

SCULPTS THE WAISTLINE sharpens the mind, massages the spirit, restores that collegiate optimism. DHEA seems almost too good for Saturday morning infomercials. So what's the catch? No one really knows. In one study, rodents given DHEA developed liver cancer, but their daily doses were ten to twenty times the amounts prescribed for humans. "If you're giving the body replacement doses, amounts it has already seen," says John Nestler, of the Medical College of Virginia, "then I think the risk of side effects in the liver is pretty low."

The real downside, doctors say, may be that DHEA simply doesn't work. Those dazzling results in animal studies, for example, may mean exactly nothing for humans. "Put it this way," says Kenneth Gorelick, the Genelabs doctor. "You can make just about anything work in some animal model. The only way to know what really happens in humans is to do experiments in humans, in vivo. As a friend of mine likes to say, 'in vivo veritas.'"

Samuel Yen has done just that, of course, but even his evidence is sparse. For one thing, his two studies included just 46 people. For another, the most pronounced effects people on DHEA report are psychological, and it's tricky to determine what, exactly, might be responsible for a person's shift in mood or well-being.

During most of the study, for example, Maria Bowman was caring for her son Louis, who was suffering from Lou Gehrig's disease. She spent hours every day helping him eat, get around, and go to the bathroom. "Just the fact that I was in this study," she says, "that I was doing something for myself for a change-that made me happy, I know."

Another woman, Nancy Martin, a 55-year-old writer and competitive runner, was in the midst of menopause during the study. "I did feel like the DHEA was helping me sleep and lessening my joint pain and soreness after running. It seemed to give me more energy, more glow, those sorts of things," she says. "But my body was changing so much during that time, who knows what was really going on?"

Certainly Elizabeth Barrett-Connor, an epidemiologist at UC San Diego and lead author of the 1986 study linking DHEA to longevity and fewer heart disease deaths, doesn't pretend to know. And until more answers are in, she's far from ready to prescribe it--let alone take it herself, as some researchers are doing. She has completed an enlarged version of the original study, following 1,029 men and 942 women over age 50 for 19 years. Contrary to her 1986 report, this study shows a weaker correlation between DHEA levels and risk of dying from heart disease. "It doesn't look quite as impressive as it did before," she says.

Though grateful that the hormone is receiving more scientific attention, Barrett-Connor says DHEA still has a lot to prove before qualifying as a legitimate anti-aging therapy. "It's been overhyped," she says. "Every five years something comes along that's supposed to solve old people's problems. It's like the flavor of the month."

NOT THAT MOST OF the people taking DHEA care much one way or the other whether the drug has been over-hyped. They say it makes them feel good right now, and possible risks be damned. "Listen," says William Regelson, the oncologist who has been taking DHEA for six years. "I just turned 70. I know there's a contract out there on me, and I'm trying to save my ass. I'm not going to wait 30 years for some graduate student to figure it out. I won't be around then."

Maria Bowman sees the benefits through the magnifying lens of her experience with her son. "When I was caring for my son, I saw what it was like for an adult to become totally dependent. You cannot believe how painful that is, how humiliating. I want no part of it."

DHEA's self-selected guinea pigs become most animated when they talk about how hormone therapy restores the small pleasures in a day. Some of it boils down to vanity. "Absolutely," says Regelson. "People say I don't look 70. I like that." But more of it has to do with growing old the way they think they should, the way they've always been told--by staying "young at heart." That phrase means different things to different people: an open mind, a sense of playfulness, curiosity, gardening, tennis lessons, tight jeans, walks in the park. But it's meaningless, says Bob Jones, if you're young at heart but prehistoric everywhere else. "You cannot go hiking or play golf if you can't get out of bed," says Jones. "It's even hard to read a book if you're dead tired, depressed. All this stuff about the golden years, about aging with grace? Biggest bunch of bull I ever heard. It's a lot easier to age with grace when your body is feeling young, feeling healthy."

Does that mean we should all go hunting for a doctor willing to write a prescription? Most researchers think there are still too many unknowns. "I'm not saying DHEA is dangerous. So far, it looks very safe," says endocrinologist John Nestler, "but we can't go recommending something we know so little about. The Hippocratic Oath says, 'First, do no harm.'"

Edmund Chein not only disagrees but believes that it's never too early to start. "You ought to start replacing as soon as you start losing," he says. "I have patients in my waiting room right now, a businessman who has brought his son in. The son is about 30, I think."

Maybe, but he looks younger: a goateed Angelino with a long ponytail, looking slick in baggy shorts and high-tops, leafing through the literature on DHEA. He could have come over on a skateboard.

PHOTO (COLOR): Maria Bowman, who'll say only that she's in her fifties, felt a new zest for life on DHEA: "I stopped finding reasons not to do things."

PHOTO (COLOR): Bob Jones, 66, now enjoys hiking rugged Mount San Jacinto: "I feel as good as I have in 20 years."

PHOTO (COLOR): "I was having trouble just getting up in the morning to run," says competitive runner Nancy Martin, 55. She credits DHEA with keeping her on track.

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By Benedict Carey

Photographs by Danny Turner

THE HORMONE HIT LIST

DHEA is one of several natural hormones that decline as we get older and whose replacement might help the body age better. Doctors prescribing "youth preservation" therapy most commonly recommend the following hormones:
HUMAN GROWTH HORMONE

When it declines: Gradually after middle age.

What replacement can do: Can cause a dramatic shift in the body's metabolism, resulting in more muscle and less fat; accelerates healing in surgical patients; and helps people get more deep sleep.

Side effects: May lead to carpal tunnel syndrome--a disabling condition often associated with repetitive hand movements. Can bring on diabetes-like symptoms and may cause gynecomastia, in which men grow enlarged, tender breasts.

How to get it: Few doctors will prescribe HGH as an anti-aging treatment. Must be injected twice a day at an average cost of $800 a month.
ESTROGEN

When it declines: Gradually in women, starting at age 40; sharply around age 50, leading to menopause.

What replacement can do: Eliminates hot flashes, sleeplessness, and other symptoms of menopause. May reduce the risk of heart disease and osteoporosis in postmenopausal women.

Side effects: Cramping, breast pain, weight gain. Some studies suggest that estrogen therapy may increase the risk of breast cancer.

How to get it: Virtually all doctors will prescribe; women who have not had a hysterectomy will be advised to take a combination of estrogen and progesterone. Pills cost from $10 to $30 a month. Estrogen alone is available by transdermal patch for about $25 a month.
TESTOSTERONE

When it declines: Gradually in men, starting at 40; in women, at 50.

What replacement can do: Increases output of growth hormone and, with exercise, strengthens upper-body muscles. Can improve mood and increase sex drive in older men and women.

Side effects: May decrease HDL, or "good" cholesterol, and boost LDL, the "bad" kind, increasing the risk of heart disease or stroke. By stimulating growth of prostate cells, may increase the risk of prostate cancer.

How to get it: Doctors have begun prescribing it to both men and women for low libido and for some conditions that cause impotence in men. Available by pill, shot, implant, or patch for $50 to $100 a month.
MELATONIN

When it declines: Sharply at adolescence, then again at about age 40; elderly adults produce only half as much as children.

What replacement can do: Eases insomnia in older adults. Animal studies suggest it may strengthen the immune system and fight cancer.

Side effects: Lingering grogginess; may worsen any existing depression.

How to get it: Not approved by the Food and Drug Administration, but sold in health food stores for $10 to $20 a bottle.

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By Benedict Carey

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