Human Growth Hormone: Fountain of youth or prescription for danger?

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Biomechanics May 2006

Human Growth Hormone: Fountain of youth or prescription for danger?

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Some practitioners advocate replacing youth's lost hormone levels in

aging adults, but researchers advise a more cautious approach.

By: Lori Rochelle Roniger

Edmund Chein, MD, used to treat patients with injuries and physical

disabilities who were also taking hormones for recognized medical

conditions, such as thyroid hormone following thyroid cancer and

estrogen after ovary removal. Trained as a physical medicine and

rehabilitation specialist, he saw striking changes in his patients

when their hormone levels improved.

" Functionally, it was day and night, " he said.

This led Chein to check the hormone levels of elderly patients who

were beginning to show signs of disability. He tested for multiple

hormones, an approach different than that of specialists who might

focus on one hormone, such as insulin.

" People who are aging are mildly deficient in all of the hormones, "

Chein said.

He began prescribing multiple hormones to aging individuals, even if

they had not had surgery, cancer, or some other trauma that led to a

reduction in hormone levels, in an effort to bring their hormones to

the levels of a normal 20-year-old. In 1994, Chein founded the Palm

Springs Life Extension Institute, based in Palm Springs, CA, to focus

on providing this type of treatment. Since then, 9000 patients have

been seen at his institute, most of whom range in age from 35 to 65.

Patients pay for services out of pocket and also purchase from the

institute bioidentical hormones, the only type Chein says he

prescribes.

Hormones Chein prescribes include growth hormone, melatonin, thyroid

hormone, and estrogen. He provided these hormones, depending on

individual needs, to the first 200 patients at the institute. In an

effort to gather research data, he advised them not to change other

things in their lives, such as exercise habits.

" Their biological age changed, " he said.

Body fat was reduced, cardiovascular fitness improved, reaction time

quickened, and the appearance of skin tone and muscles improved,

Chein said.

Of 1000 institute patients prescribed human growth hormone who were

sent self-assessment surveys, 202 responded. He reported the results

in the Fall 1999 issue of the Journal of Advancement in Medicine.

More than 50% of the respondents reported improvements in strength,

exercise endurance and tolerance, body fat, back flexibility, and

other factors.

Chein sometimes sees such side effects as joint pain and swelling,

known to occur with growth hormone, in his patients but says he is

able to eliminate them by adjusting dosage levels.

So why isn't everyone over the age of 35 taking growth and these

other hormones? For one thing, the cost-approximately $8000 to

$20,000 annually-which patients pay out of pocket without any

insurance reimbursement, if the prescription is for antiaging.

Additionally, researchers studying growth hormone at various academic

institutions say that current scientific knowledge does not yet

support its use in aging adults without major hormone-related

disorders. They add that use of the hormone in these individuals has

side effects like fluid retention, joint pain, and worsening glucose

tolerance that with long-term use could potentially lead to more

serious problems such as arthritis or heart failure. Individuals

suffering from acromegaly, a condition caused by the overproduction

of growth hormone, are at increased risk for osteoarthritis,

diabetes, hypertension, and cardiovascular disease.

Same studies, different conclusions

Practitioners like Chein and others who prescribe growth hormone

injections-the only dosing method believed by practitioners and

researchers to allow the body to effectively use the substance-to

aging adults like to point to the handful of studies demonstrating

the benefits of growth hormones. Some practitioners reference a

fairly well-known study on the effects of human growth hormone in men

older than 60 led by Medical College of Wisconsin researchers in

Milwaukee and the late Rudman, MD, which was published in The

New England Journal of Medicine in 1990. Other studies that are used

to promote the use of growth hormone for aging include a 1999 NEJM

review article on growth hormone use written by Lee Vance, MD,

currently a professor of internal medicine and neurosurgery and

associate director of the General Clinical Research Center at the

University of Virginia, and Nelly Mauras, MD, now at Nemours

Children's Clinic in ville, FL.

The Vance article discusses growth hormone use in adults with

clinically diagnosed growth hormone deficiency but not in aging

adults with declining levels of the hormone associated with normal

aging.

" It's really irritating, " Vance said of the use of her study to lend

support to the hormone's prescription for aging. " The 1999 article

does not support growth hormone use for antiaging. It is a

comprehensive review of the clinical studies done in people with

pituitary disease and loss of pituitary function who are growth

hormone-deficient. "

It is normal for growth hormone levels to fall with age, Vance said.

" That's Mother Nature. No one knows why as we get older we produce

less growth hormone. There must be some benefit in it, " she said,

pointing to studies done in growth hormone-deficient transgenic mice

that have found they live longer than normal mice.

The bodies of healthy men and women in their 30s and onward release

progressively declining levels of growth hormone and IGF-1 (insulin-

like growth factor 1), said Marc R. Blackman, MD, chief of the

endocrine section at the National Institutes of Health's National

Center for Complementary and Alternative Medicine and a researcher on

the use of growth hormone in healthy aging adults. By the time they

are in their 60s and 70s, adults produce only one-third to one-half

of the growth hormone that they did in their 20s and 30s, he said.

However, research is still determining how much of a factor these

hormonal declines are in the tendency for muscle strength to

decrease, bone to thin, and body fat to accumulate in the abdominal

area with age.

The 1990 Rudman study found that healthy men aged 61 to 81 with

growth hormone insulin-like growth factor I (IGF-I) levels of less

than 350 U per liter who were given HGH for six months experienced an

8% increase in lean body mass, a 14.4% decrease in adipose-tissue

mass, and a 1.6% increase in average lumbar vertebral bone density,

all significant changes. Thirty percent of healthy men the age of the

study subjects have growth hormone levels below 350 U/L; levels in

healthy men aged 20 to 40 are typically 500 to 1500 U/L.

" The findings in this study are consistent with the hypothesis that

the decrease in lean body mass, the increase in adipose-tissue mass,

and the thinning of the skin that occur in older men are caused in

part by reduced activity of the growth hormone-IGF-I axis, and can be

restored in part by the administration of human growth hormone, " the

researchers wrote. " The effects of six months of human growth hormone

on lean body mass and adipose-tissue mass were equivalent in

magnitude to the change incurred during 10 to 20 years of aging. "

However, the authors recommended further research, noting that

questions remain to be answered: " What will be the benefits and what

will be the nature and frequency of any adverse effects when larger

numbers of elderly subjects and other doses of human growth hormone

are studied? What organs are responsible for the increase in lean

body mass, and do their functional capacities change as well? Only

when such questions are answered can the possible benefits of human

growth hormone in the elderly be explored. Since atrophy of muscle

and skin contributes to the frailty of older people, the potential

benefits of growth hormone merit continuing attention and

investigation. "

The investigators also advised research on growth hormone use over

longer periods of time in older men before reaching final conclusions

about its efficacy.

In an editorial that ran in the same NEJM issue, Vance cautioned that

the results should be considered preliminary and that additional

research was required on the potential side effects, dosing, and

optimal time for beginning HGH treatment in older adults with

declining production of the hormone.

" Growth hormone can affect carbohydrate metabolism adversely

(producing hyperinsulinemia, glucose intolerance, and diabetes

mellitus), the musculoskeletal system (producing arthritis and

arthralgia) and the cardiovascular system (producing hypertension,

edema, and congestive heart failure), as exemplified by acromegaly, "

she wrote.

Researchers recommend ... more research

Blackman also supports continued research on growth hormone before it

is used in healthy older adults. A study he led that was published in

the Journal of the American Medical Association in 2002 found that

women and men ages 65 to 88 given growth hormone for 26 weeks

experienced increased lean body mass and decreased fat mass. Men who

received both growth hormone and testosterone saw a marginally

statistically significant increase in muscle strength and

statistically significant improvement in cardiovascular endurance

capacity, both of which were directly related to changes in lean body

mass.

" Studies show that the amount of muscle increases, " Blackman said of

his and other growth hormone studies. " But not a single one shows an

increase in strength or functional usefulness. "

Blackman's study found a significant increase in edema in women

taking growth hormone, carpal tunnel symptoms in men taking a

combination of growth hormone and testosterone, and arthralgias in

men taking growth hormone only. These side effects, which can be

reversed by adjusting dosages and stopping use of the drug, have been

found in previous growth hormone studies. More troubling, however, is

a tendency toward a diabetic pattern in growth hormone users. The

Blackman study detected a statistically significant increase in

diabetes or fasting glucose intolerance in male subjects who received

growth hormone compared to those who did not.

Other concerns of Blackman and other researchers include the

potential for growth hormone to cause or accelerate cancer.

Acromegaly has been associated with an increased risk of colon and

other types of cancer. Growth hormone could also theoretically

shorten life, a possibility based on the observation that transgenic

mice with increased growth hormone have shortened life spans. On the

other hand, growth hormone deficiency in humans is definitely

associated with increased mortality.

" We don't know enough about functional outcomes or long-term safety, "

Blackman said. " Until we learn more, I would not recommend the use of

recombinant growth hormone outside of carefully controlled clinical

studies. "

He also pointed out that what may be the best growth hormone dosage

for aging bones may turn out not to be the best one for brain

function, for example, and that not enough is known about the optimal

dosage level to maximize effectiveness and minimize side effects.

For now, Blackman recommends that along with choosing one's parents

carefully (in order to take advantage of longevity benefits believed

to be genetically conferred), people adopt healthy behaviors that

don't have adverse side effect profiles, like eating well, refraining

from smoking cigarettes, not consuming excessive amounts of alcohol,

and participating in exercise, including weight-bearing activities.

" Sneakers are cheaper, " he said, referring to the uninsured cost of

growth hormone.

Growth spurt

Since the publication of Rudman's article in 1990, the antiaging

industry and the prescribing of growth hormone for aging have boomed,

although research on growth hormone use in aging adults has not

significantly advanced.

Vance wrote in another NEJM editorial in 2003, " Studies that have

followed the 1990 report by Rudman et al confirm the effects of

growth hormone on body composition but do not show improvement in

function. In contrast, resistance training improves muscle strength

and function, indicating that real effort is beneficial. There is no

current 'magic-bullet' medication that retards or reverses aging. It

remains to be determined whether growth hormone secretagogues that

consistently increase endogenous production of growth hormone are

beneficial in the elderly. Antiaging therapy with growth hormone has

not yet been proved effective according to objective outcome

criteria. "

Although some researchers would like to see longer term studies

conducted on growth hormone use in aging adults, well-controlled

studies have not been performed by practitioners who prescribe the

treatment and significant funding has not come through for university-

based researchers to perform the work.

" To my knowledge, there are no long-term studies on administering

growth hormone to middle-aged or older people to see the risks and

benefits, " Vance said.

In addition, researchers including Vance say that not only is the

current prescription of growth hormone to treat aging not

scientifically supported, but it is also illegal.

" Until growth hormone is properly studied, it's premature to be using

it as an intervention, " said S. Jay Olshanksy, PhD, a professor of

public health at the University of Illinois at Chicago and a

researcher on aging. " There may be a time to use it in the future,

once it is evaluated with clinical trials. It is illegal to be using

it as an antiaging intervention. "

He ticks off what is currently known about growth hormone. It

increases muscle mass but with no proven increase in strength. It

reduces body fat and improves skin elasticity but there have been

side effects associated with its use.

" You can get these benefits for free with exercise-without the side

effects, " Olshansky said.

And he points out that some of the clinics that prescribe growth

hormone also recommend the adoption of new exercise routines and

diets, so that the benefits said to be seen in patients could be due

to these factors.

As to claims of the antiaging powers of growth hormone, which even

many proponents of its use say is unproven?

" There is no proof that it makes you live longer, " he said. " It might

make you live a shorter life. "

Legal spats

Olshansky's position and advice sound simple but he has managed to

fuel the ire of antiaging medicine proponents. M. Klatz, MD,

DO, president and cofounder of the American Academy of Anti-Aging

Medicine (A4M), and M. Goldman, MD, PhD, DO, chair of the

organization's international operations, filed a lawsuit in 2005

against Olshansky and Perls, MD, MPH, an associate professor

of medicine and geriatrics at Boston University, claiming

professional defamation.

Perls, who is studying centenarians for a model of successful aging,

equates the use and selling of growth hormone by antiaging medicine

practitioners and promoters to the hawking of snake oil and other

promises of eternal youth.

Perls and Olshanksy have reportedly presented a bottle of actual

snake oil at a conference to the antiaging pair, who were not

present. The lawsuit's defendants also were part of the guest editing

team for a 2004 issue of The Journal of Gerontology: Biological

Sciences on antiaging therapies that, among other topics, discussed

the legal issues surrounding " quackery in the antiaging industry " and

included an article by Blackman and S. Harman, MD, PhD,

director and president of the Kronos Longevity Research Institute of

Phoenix and a coauthor of the 2002 JAMA study, mentioning Klatz and

Goldman by name.

The A4M duo had written after the JAMA study's publication that the

effectiveness and safety of growth hormone had already been

established in older adults by other studies and that the adverse

effects reported in the study were due to doses that were higher than

those typically prescribed by antiaging physicians. Blackman and

Harman responded in their Journal of Gerontology article that seven

of the eight studies mentioned by Klatz and Goldman were conducted in

people with pituitary disease who met the criteria for adult growth

hormone deficiency. The remaining study was Rudman's 1990 article,

which Klatz and Goldman said showed gains in lean body mass,

decreases in fat, and increases in bone density. However, Blackman

and Harman wrote in their article that bone density was not

significantly affected by the treatment.

The study, in fact, found no changes in bone density of the radius or

proximal femur of the subjects but a significant increase in lumbar

vertebrae density. However, this change was only 1.6%, which the

authors wrote was statistically significant only because of the

minimal variability in individual results.

Growth hormone use continues

Chein is far from the only physician prescribing growth hormone to

aging adults. For one, Alan Mintz, MD, chief medical officer, CEO,

and cofounder of Cenegenics Medical Institute of Las Vegas, NV,

prescribes growth hormone, as well as other hormones and dietary and

exercise changes to aging patients.

" We never-underline never-use growth hormone in a vacuum, " Mintz

said.

He emphasized that his clinic practices age management medicine and

is not part of the antiaging movement. Seven percent of Cenegenics'

total patient base takes growth hormone, Mintz said, adding that the

clinic prescribes the hormone only " on label " for adult growth

hormone deficiency. Cenegenics has seen a total of 12,000 patients.

Estimates are that 35,000 U.S. adults suffer from growth hormone

deficiency.

" We really believe in the synergy of nutrition, exercise, and

hormonal therapy, " Mintz said. " That's when you really get success. "

Mintz has studied the outcomes of his patients taking hormones

(androgens, or masculinizing substances-of which the primary and most

well known one is testosterone-alone or in combination with growth

hormone in men or androgens in combination with growth hormone and/or

hormone replacement therapy in women) but their therapies have also

included dietary and exercise modifications and no control or placebo

group was included. He has found self-reported improvements in his

patients in lean muscle mass, body fat levels, athletic performance,

strength, exercise capacity, and energy, and side effects like

swollen joints, arthralgias, and swollen feet and hands.

Mimicking the body's natural patterns

The state of research on growth hormone remains anemic but perhaps

the point will end up moot. University-based researchers around the

country have been collaborating on a multicenter study on the use in

healthy older people of a growth hormone secretagogue, a substance

which causes growth hormone to be released in a pattern that more

closely resembles the body's natural pattern. Injecting growth

hormone artificially increases the hormone levels in a static

pattern, but naturally occurring hormone in the body is released in

spurts throughout a 24-hour cycle, producing highs and lows of the

substance.

It's safe to say that the use of growth hormone in aging adults isn't

going away any time soon and that the substance is unlikely to prove

a fountain of youth. With growth hormone garnering recent attention

from mainstream media like GQ, Business Week, and the Associated

Press, and advertisements for ordering it via the Internet commonly

arriving as unsolicited spam e-mail, biomechanics practitioners may

encounter patients and acquaintances inquiring about its effects-or

become curious about its potential benefits for themselves.

Unfortunately, funding for research on growth hormone for aging has

never gained much momentum. Early adopters and risk-takers may

believe there's enough evidence already for them to prescribe or use

HGH, but unfortunately it remains to be seen whether HGH can produce

biomechanical benefits like improvements in bone strength and the

ability to perform activities of daily living or if it's a new

version of snake oil not only in marketing terms but also in the

severe health risks its use carries.

In the meantime, investigators continue to search for elusive

substances-studying some, like chocolate milk, that are relatively

inexpensive and appear to have minimal potential downsides-that may

help preserve muscle and physical function as we inevitably age.