Growth Hormone – the Fountain of Youth!?
Adapted from an article that appeared in the Star on 11 Dec 2005

Dr Hew Fen Lee
Consultant Endocrinologist
Chairman, Committee for Consensus for Growth Hormone use, Malaysian Endocrine & Metabolism Society and the Academy of Medicine

Dr Arlene Ngan
Consultant Endocrinologist
Member, Committee for Consensus for Growth Hormone use, Malaysian Endocrine & Metabolism Society and the Academy of Medicine

‘The fountain of youth- growth hormone’. The headline screams out of the newspaper. The article from the newspaper with the accompanying advert in the same page have described the medical and scientific evidence of the anti ageing effect of growth hormone (GH) and its many virtues of bringing about almost eternal youth. There is an intense interest in products that extend longevity and more so bring about a near eternity youthfulness. Rumours abound of certain public figures or film stars being on some products that may be accountable for their youthful looks or physical fitness or even their success.

In fact such interest in immortality is not new or recent. One of the legends of the Chinese Mid-Autumn festival (Mooncake Festival) describes a beautiful maiden in the moon called Chang Er. The story behind her ending up there is because of her tyrant husband who was a king. He spared no effort in looking for a drug for immortality oblivious of the suffering of his subjects. After a long search, a drug was finally found but Chang Er was worried that her husband may bring more suffering for people if he took the drug and lived forever. She took the drug herself instead and after taking it she floated to the moon.

What is GH?

GH is a peptide hormone which is made up of mainly amino acids that are also the building blocks of protein. This is similar to other peptide hormones for example, insulin which means that should one need to administer it, it has to be given by injection rather than taken by mouth. GH is normally made in the pituitary gland and the secretion is controlled by a complicated system of check and balances that requires other hormones eg somatostatin and GH releasing hormone through the hypothalamus. It is released from the pituitary gland mainly during sleep (Hartman, 2000).In life it has one main function which is to promote growth during childhood and puberty. The way it does this is working directly as well as indirectly through another hormone known as insulin like growth factor I (IGF-I). We know that children who lack GH are short and replacing the hormone brings about a normal growth pattern.

As we age, many hormones in our body reduce gradually except for oestragen during menopause in women where the reduction is quite dramatic. The other hormones that are shown to be reduced with age include GH, IGF-I, testosterone in men and DHEA-S. The natural assumption is that by restoring such hormones to the levels in the younger days would also reverse the process of ageing. This is a reasonable assumption but not all hormones seem to follow that hypothesis. Hormone replacement therapy with oestrogen certainly has been used for many years and recent study has indicated the higher risk of breast cancer which has brought some caution in its use as a panacea for health and beauty.

Does GH have any anti-ageing effect?

It has been noted that adults with GH deficiency with a reduced GH and IGF-I levels in the body have been found to have muscle wasting and an excess of abdominal fat (Hew et al, 1998). This body composition changes can be reversed by the administration of GH. What is interesting is that the lethargy that some of these people with GH deficiency have, seemed to be improved by GH treatment. Furthermore, there are many changes in the metabolism in those with GH deficiency for example, high cholesterol level, osteoporosis may also be improved by GH replacement.

Normal aging is also associated with the same body compositional and metabolic changes and many elderly people do complain of lethargy. Besides GH and IGF-I levels are also lower in the elderly. On the other hand, the difference in GH and IGF-I levels between the young and elderly adults is fairly small compared with the very low levels found in those with GH deficiency (Toogood & Shalet, 1998). It was speculated that GH injection may improve some of the changes in the body that are associated with aging. Several studies have since been conducted showing some favourable results with GH injection in healthy elderly people with a proven low IGF-I levels over short periods. There was a reduction of fat in the body coupled with an increase in muscle mass although the muscle strength was not improved (Rudman et al, 1990; Holloway et al, 1994). A lot of the improvement in the muscle is due largely to an increase in water content in the muscle rather than an increase in muscle cells or muscle fibres. There was however NO improvement in the feeling of well being and a lot of those who took part complained of pain in the joints which is a known side effect of GH (Rudman et al, 1990; Holloway et al, 1994). This side effect can be reduced with a smaller dose of GH, but the benefits in body composition will also be reduced too. The improvement in the lipid levels and bone mass is negligible. There is presently little data to assess its anti-ageing effectiveness over a period longer than 6 months.

Is GH harmful?

In any treatment, the main concern is the side effect(s) if there are any. GH has been used for years in children who lack GH. There has not been any evidence of any long term side effect especially with regards to cancer risk. Having said that, most of these younger patients receive treatment for only a relative short period of time averaging a few years. There are some side effects which include ankle swelling, carpal tunnel and joint pain but generally, they are fairly mild (Rudman et al, 1990; Holloway et al, 1994; O’Connor & Blackman, 2000). In older adults with GH deficiency, GH replacement, in addition to the side effects mentioned-above, causes a small increase risk of hypertension and diabetes (Hew et al, 2000). It can even make existing heart failure worse. These are side effects recorded in those who have GH deficiency and thus are given GH as a replacement. The side effect may be even worse in those who have close to normal GH level given a supplement dose rather than replacement dose of GH. Presently, there are no long term safety data in elderly healthy individuals who have near normal or even normal GH levels given GH treatment.

There are obviously several concerns:

1. Older people are more prone to getting diabetes and hypertension, thus the increased risk seen in the younger GH deficient patients may be even worse in the elderly.
2. Though there has not been any evidence of an increased cancer risk in the younger GH deficient patients, this is not known in the elderly who are not GH deficient. It must be noted that the older people are more at risk of developing cancer of various kinds. GH is known to promote growth which includes the growth of cancer cells. For this reason, many medical and scientific researchers utilise GH for cancer research. There are also some other concerns too. Firstly, it has been found that while the IGF-I levels may be lower in many elderly people, those who have higher but yet within normal IGF-I levels in this age group have an increased risk of prostate cancer in men. A more recent study from Singapore shows an increase of breast cancer in those who produce a high albeit normal level of GH. By increasing the IGF-I level or the GH level can theoretically cause an increase cancer risk even if the level is within what we regard as acceptable range.
3. Furthermore, it has been observed that  people who develop a rare tumour in the pituitary gland that produce excessive amount of GH- a condition known as acromegaly, have a 2-3 times higher risk of developing colon cancer. The risk of hypertension, diabetes and heart failure is also many times higher.

Given the various concerns above, we need to conduct a proper study to find out if GH is safe for longer term use and to find out if the benefits shown in short term use are sustained (Rudman et al, 1990; Holloway et al, 1994; O’Connor & Blackman, 2000).

If GH can have side effects, would substance(s) that increase GH secretion (GH secretagogue) have some anti-ageing effect?

At the time of publishing of this article, several drugs are being developed to enhance or augment the depressed GH secretion due to old age. Some of these drugs eg GHRP, MK-677, hexarelin have been shown to be effective in increasing the natural GH secretion but to date we don’t know if this increase in GH secretion brings about any benefit. There seems to be a small improvement in body composition (much less than that of GH injection) but there is also a small increase in blood glucose level and thus the risk of diabetes (Chapman & Thorner, 2000). Some amino acids eg arginine when given intravenously, has been shown to increase GH secretion for only a short period of time. However, oral amino acids have not been shown to have the same effect much less a piece of meat, given that meat is made up of protein which in turn is made up of amino acids (Chapman & Thorner, 2000).

We need to keep in mind the aim of the treatment which is not only to prolong life but also to preserve vitality and youth. So far this has not been made available from medications or supplements that are proven both in terms of its effectiveness and its safety. Healthy and happy lifestyle remains the most effective and ignored regimen that we have. Regular exercise coupled with sensible diet adjustment is the mainstay of staying young. If we resort to taking any form of treatment, not only must we be certain of its effectiveness, we also need to know its side effect profile. Similarly, the use of GH for anti-ageing purpose has been fuelled more by misplaced enthusiasm rather than concrete evidence of its effectiveness and safety. If Chang Er knew that the side effect of the longevity medicine is to float to the moon, I am sure she would be quite happy for her tyrannical husband to take the medicine and live forever in the moon away from the oppressed people.

Reference

Chapman IM & Thorner MO. (2000) Clinical use of growth hormone releasingnpeptides (GHRPs) and GHRP analogues in adults. In Growth hormone in adults: physiological and clinical aspects. Ed: Juul A & Jorgensen OL. Second edition. Cambridge University Press.

Hartman ML. (2000) Physiological regulators of growth hormone secretion. In Growth hormone in adults: physiological and clinical aspects. Ed: Juul A & Jorgensen OL. Second edition. Cambridge University Press.

Hew FL, O’Neal D, Kamarudin N, et al. (1998) Growth hormone deficiency and cardiovascular risk. Bailliere’s Clinical Endocrinology and Metabolism. Vol 12: 199-216.

Hew FL, Christopher M, Alford FP. (1998) Growth hormone deficiency, insulin resistance and glucose metabolism. In Growth hormone in adults: physiological and clinical aspects. Ed: Juul A & Jorgensen OL. Second edition. Cambridge University Press.

Holloway L, Butterfield G, et al. (1994) Effect of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. Journal of Clinical Endocrinology and Metabolism. 79: 470-479.

O’Connor KG & Blackman MR. (2000) Growth hormone and ageing. In Growth hormone in adults: physiological and clinical aspects. Ed: Juul A & Jorgensen OL. Second edition. Cambridge University Press.

Rudman D, Feller AG, et al. (1990) Effect of human growth hormone in men over 60 years old. The New England Journal of Medicine. 323:1-6.

Toogood AA, Shalet SM. (1998) Ageing and growth hormone status.  Bailliere’s Clinical Endocrinology and Metabolism. Vol 12: 281-296.