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The search for eternal youth has been long and disappointing. Down the
ages, any number of potions have been tried with no great success. But
the obvious appeal attached to slowing the march of time, coupled with
concerns from Western governments about escalating healthcare costs for
ageing populations, has kept research interest alive. Now, it seems that
mainstream scientists may be on to something good.

This time the potential elixir of youth is human growth hormone. Research
is starting to hint at a role for it in the treatment of everything from
heart disease to depression, obesity to muscle weakness, metabolic disturbance
to a rundown immune system. Many of these conditions are associated with
increasing age. Some enthusiastic researchers believe the hormone is so
successful in reversing aspects of ageing that it could eventually become
a virtually universal prescription for elderly people.

Others, however, are more circumspect. They say there is a fine but
important line between treating illness associated with ageing, and treating
ageing itself. Their main concern is that healthy elderly people may have
adverse reactions if they take growth hormone supplements even for a few
months. Excess human growth hormone does have well-known side effects including
acromegaly, in which people develop a prominent jaw and enlarged hands and
feet. And recent research has uncovered a link with carpal tunnel syndrome
and diabetes. Even the most enthusiastic researchers have been tempered
by such views as they carefully weigh the risks and the benefits of the
growth hormone supplements.

PREMATURE EXCITEMENT

However, this painstaking approach is in danger of being overtaken by
a premature and over-enthusiastic response from the public. The promise
of extended if not eternal youth is beguiling and some people are not prepared
to wait for the results of trials. Already some in the US are bypassing
normal medical care to gain access to the hormone. Researchers are concerned
that taking the hormone without proper supervision might be dangerous.
Any problems would besmirch the name of promising new research, they say.

Growth hormone has been known about since the late 1950s, when it was
discovered in the pituitary gland which produces it. Early supplies of the
hormone had to be extracted from cadavers and was desperately scarce worldwide.
So, for many years, doctors agreed that it should be reserved for the treatment
of young children who could not produce their own hormone. Such children
fail to grow to a normal height. By administering growth hormone before
puberty, when the cartilaginous end plates of the bone, or epiphyses, fuse,
dramatic improvements are achieved. However, this policy meant that research
into the effects of growth hormone on other groups of people was not possible.

Then, in the late 1970s, came reports of the synthesis of human growth
hormone in the laboratory. For the first time, the relative abundance of
the hormone allowed doctors to look at its effects on adults. Initial tests
were done on adults with serious deficiency – following treatment for pituitary
tumours with surgery or radiotherapy, for example. This research, and subsequent
studies on normal ageing adults, has challenged the previously held assumption
that the hormone’s uses are essentially confined to childhood.

According to Daniel Rudman, a key US researcher in human growth hormone
and professor of geriatrics and gerontology at the Veterans Affairs Medical
Center in Milwaukee, normal levels of human growth hormone are closely related
to stages in development. Levels are high in the fetus and decline throughout
early childhood. A surge of hormonal activity at puberty corresponds with
the period of rapid growth. But here the information on growth hormone
collected by paediatricians stopped.

‘We wanted to fill in the picture,’ says Rudman. ‘We wanted to see what
happens in early, middle and late adulthood.’ What they discovered was that
after the prime of life, decade by decade, the production of growth hormone
declines. And, according to Rudman, in late adulthood, somewhere between
60 to 90 years, people have a so-called somatopause, after which only tiny
amounts of growth hormone are produced. He compares this with the menopause
in women when levels of sex hormones tail off dramatically. Deficiency
in growth hormone appears to be widespread among elderly people, he says.

Rudman reasoned that just as age-related deficiencies in oestrogen can
be made good with hormone replacement therapy, so the same approach might
work for growth hormone. ‘Some aspects of the ageing process can’t be changed,’
he says. But he believes that the ageing of the endocrine system – those
glands including the pituitary which release hormones directly into the
bloodstream – may be treatable. The first step in validating this approach
is to assess exactly which body functions growth hormone controls and how
it works.

From the early studies of adults with growth hormone deficiency, a striking
and consistent observation was the effect of growth hormone supplements
on body composition. Children deficient in the hormone are not only short
but have an abnormal increase in fat mass, especially around the middle,
and a decrease in lean tissue. Hormone-deficient adults have a similar build.
Small-scale but detailed studies worldwide have shown that treatment with
the hormone can rapidly and dramatically reverse this abnormality.

DRAMATIC EFFECTS

In 1989, researchers at St Thomas’s Hospital in London studied 24 hormone-deficient
adults most of whom had been treated for tumours of the pituitary gland.
They found that the patients’ body weight was constant before and after
six months of treatment. But they lost an average of 5.5 kilograms of fat,
and increased their lean body mass by a comparable amount. Similar findings
have come from other studies. In 1993, Swedish researchers led by Bengt-Ake
Bengtsson at the University of Gothenburg found that adults with growth
hormone deficiency who were treated lost 30 per cent of their abdominal
fat but only 13 per cent of peripheral fat.

Other studies in hormone-deficient adults have shown significant increases
in their metabolic rate, which may partly be explained by the increase
in lean tissue. They have also shown decreases in cholesterol levels, increased
muscle tone, and small but significant increases in cardiac output. One
British study even showed an improvement in the psychological states of
the patients.

So, how does one hormone have such dramatic and diverse effects? The
classical view is that human growth hormone is produced by the pituitary
gland, travels in the blood, and stimulates the liver to produce insulin-like
growth factor 1, or IGF-1. This intermediary is then responsible for most
of the hormone’s growth-promoting activities in tissues throughout the body.
According to Andrew Weissburger, a research fellow in endocrinology at St
Thomas’s Hospital, this view has been challenged by increasing evidence
that growth hormone may induce local production of IGF-1 by cells in cartilage,
muscle and other organs. Some of its apparently direct effects could be
due to locally-produced IGF-1.

The effects of IGF-1 differ from one tissue to another. It acts on muscle
cells to stimulate the production of protein and manufacture of cell components.
It mobilises fat for use as energy in adipose tissue. It prevents insulin
from transporting glucose across cell membranes in lean tissue, so that
the cells have to switch on their mechanism for using fat for energy. As
a result, glucose levels in the blood may rise.

MEDIA ATTENTION

Elsewhere, Douglas Crist, a physiologist at the department of endocrinology
at the University of New Mexico, believes growth hormone has a different
effect again on the immune system. He has demonstrated an increase in the
function of killer cells in people given the hormone. Samples taken from
healthy adults were better able to kill cancer cells in culture after they
had been given growth hormone.

By the mid-1980s, the evidence showing the wide-ranging effects of human
growth hormone started to kindle interest in its potential benefits for
healthy elderly people. Researchers in the US led the way, with Rudman in
the forefront. In July 1990, he published results from a landmark study
in the New England Journal of Medicine. Rudman’s analysis included 21 healthy
men over 60 all of whom were beyond the so-called somatopause, and producing
extremely low levels of growth hormone. They had the reduced lean body mass,
increased fat and thin skin characteristic of their age. After receiving
the hormone for six months, all these aspects of ageing were reversed. Rudman
demonstrated an increase in lean tissue and decrease in fat ‘equivalent
in magnitude to the changes incurred during 10 to 20 years of ageing’.

Not surprisingly, this finding generated great excitement. The US National
Institutes of Health called for applications for research proposals into
the effectiveness of specific interventions in ageing, such as exercise,
nutrition and hormones, including growth hormone. It is now funding eight
projects on growth hormone in the elderly. And, in parallel to increased
research interest, came a surge in public interest. Here was a treatment
which could apparently turn back the wheels of time. Media reports of elderly
people suddenly feeling half their age were widespread. Stories of people
with new levels of energy and restored sex drive were rife.

The publicity has inspired some businessmen to set up clinics outside
the US in unregulated countries. After visiting such clinics, clients can
have personal supplies of the hormone shipped to them at their homes. Researchers
find this development extremely worrying. For example, Marc Blackman, head
of gerontology research at the Francis Scott Key Medical Center in Baltimore,
believes the claim that growth hormone improves strength has yet to be substantiated.

Blackman is an enthusiast for growth hormone, but he warns: such clinics
‘may be moving in a direction which could be harmful to the general public.’
His misgivings about the safety of long-term use of growth hormone supplements
is shared by Rudman, who says that more work into the safety and efficacy
of growth hormone will have to be completed before growth hormone is licensed
for this use. ‘In this country the FDA is nowhere near releasing it for
general use by physicians.’

Already research has found no shortage of side effects. In a study by
Rudman, more than one in four elderly men receiving the hormone for a year
developed carpal tunnel syndrome, hyperglycaemia (abnormally high levels
of sugar in the blood), or gynaecomastia (enlargement of the breasts). He
also found that these effects increase with increased dose. ‘The appropriate
dose of human growth hormone in older people is substantially lower than
was originally thought,’ says Rudman. However, the optimum dose and duration
of treatment is still being worked out. The target groups who will benefit
most are being sought, and the ways in which they will benefit evaluated.
‘We need a number of years’ experience before this is a safe, logical and
effective form of treatment,’ he says.

Other researchers are less optimistic. Andrew Hoffman at the Veterans
Affairs Medical Center in Palo Alto has doubts about growth hormone’s potential
in healthy elderly people. He says side effects like oedema and headaches
are very common even at low doses. Bell’s palsy, in which one side of the
face ‘freezes’, has also been associated with the hormone.

TONIC OF YOUTH?

‘The real issue is: if you have people who are basically healthy, does
it make sense to give them a relatively powerful hormone?’ asks Hoffman.
He believes the benefits of human growth hormone supplements would need
to be substantial to outweigh the risks. Hoffman is sceptical about the
big claims made for growth hormone. ‘There may be room for it in some cases,
but it’s not clear to me we are seeing dramatic effects.’ Weissburger, who
is now researching the effects of the growth hormone in elderly patients,
agrees. ‘I don’t think it will be a tonic of youth. There are physical benefits,
but none of the patients I have seen have reported dramatic changes in
the way they feel. They don’t suddenly want to go cartwheeling down the
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There are practical problems, too. Hoffman believes the price of growth
hormone is currently prohibitive for anything but experimental studies.
Furthermore, it must be administered by injection, which Hoffman feels
would be a barrier to its widespread acceptance by the public.

Whether the optimists or the pessimists prove correct, only time will
tell. Meanwhile, those involved in research are agreed that attempts to
exploit the technology for commercial ends are premature. Far from offering
eternal youth, unregulated use of human growth hormone may endanger promising
research, and perhaps even people’s lives.

Helen Saul is a journalist specialising in health and medical issues.