What is Growth Hormone (hGH)?

Growth Hormone is a protein, a string of 191 amino acids [1], that is produced in the pituitary gland of the brain. It is not a steroid.
hGH is released from the pituitary in pulsatile waves lasting minutes throughout the day, but the major amount is released at night during deepest sleep, when pulses last 1½ to 4 hours and are of greatest amplitude [2,3,4].

After hGH is released by the pituitary, it flows with the blood downstream to the liver, where it stimulates the production of another hormone, called Insulin-like Growth Factor-1 (IGF-1) [5].

It is IGF-1 that causes a majority of the beneficial effects associated with hGH [6].

Growth Hormone, like most hormones decrease with aging. “From young adulthood to midlife, GH secretion decreased by nearly 75%.” [7]

“Adults with growth hormone deficiency have increased fat mass, reduced muscle mass and strength, smaller hearts and lower cardiac output, lower bone density, and higher lipid concentrations. They also have decreased vitality, energy, and physical mobility; emotional lability; feelings of social isolation; and disturbances in sexual function, despite adequate correction of hormonal deficiencies other than growth hormone deficiency.” [8]

This constitutes a deficiency syndrome which is reversed by supplementation with recombinant human Growth Hormone [9].

The point of Bio-Identical Hormone Replacement Therapy is to recover lost function, and to thereby gain health benefit.

Since 1985, human Growth Hormone (hGH) has been produced using “recombinant DNA technology”. A specific strain of the bacterium, Escherichia coli, has been genetically modified to produce an exact copy of hGH [1,10].

The first reports that administration of hGH to older individuals provided increased quality of life were published in the New England Journal of Medicine in 1990 [11] and the journal, Hormone Research, in 1991 [12] both by lead author, Daniel Rudman, MD of the Medical College of Wisconsin.

Growth Hormone comes to public attention now and then because of some shocking revelation in the popular media concerning athletes or celebrities. In this way, hGH has gotten the reputation of being a substance that engenders abnormally superior physical performance in athletic endeavors, but has no other value.

I disagree with such a shallow, sensationalistic point of view. The hype serves to hide the reality. It casts an illusion.

Supplementation with Growth Hormone, along with the other hormones of youth, plus nutrition and exercise, altogether provide enhanced quality of life during the aging process. And, that is the point of the original Rudman articles.

Growth Hormone is involved with growth early in life, as you might imagine, but also healing. My hormone teacher, Neal Rouzier, MD, has consistently referred to Growth Hormone as “Healing Hormone”, a substance promoting repair [13].

As well, “A key systemic regulatory hormone is growth hormone (hGH), which has a developmental role in virtually all tissues and organs.” [14]

“Growth hormone affects somatic growth, sexual maturation, body composition and metabolism, as well as aging and longevity.” [7]

It’s important to remember that a hormone is a substance naturally produced in the body that takes messages to other parts of the same organism. To emphasize, the term “hormone” should be reserved for signaling substances naturally produced in the body. Pharmaceuticals that are not produced in nature but attach themselves to hormone receptor sites should not be referred to as “hormones”.

Thus, if a low level of a hormone is measured in the body, supplying additional amounts to produce an optimal, youthful level is “supplementation.” Giving an unnatural pharmaceutical does not resolve any deficiency.

As well, taking excess amounts of a natural hormone that is way above what is seen in youth is in itself, unnatural, and can cause harm.

It is true that at least some elite athletes are using excessive, supra-physiological amounts of hGH for purposes of enhancing athletic performance. And I am not advocating that kind of irresponsible and dangerous activity.

I am advising restoration to youthful levels for the purpose of health benefit.

What causes deficiency of a hormone, such as hGH?

There may be a congenital deficiency as in a child who has abnormally low stature. Supplying Growth Hormone (hGH) in amounts naturally seen in childhood causes linear growth of bones to occur, resulting in the eventual production of normal height.

Patients with AID’s have a wasting syndrome accompanied by growth hormone deficiency. They are well known to benefit from supplementation with hGH.

Adults may have normal production of hGH until suffering head trauma (as in football) or as the result of a pituitary tumor that has been removed.

These last 3 situations are referred to as “Adult Onset Growth Hormone Deficiency”.

But, there is another type of deficiency of Growth Hormone, that is also seen with almost all other hormones. And that deficiency is age related decline.

That is, Growth Hormone production decreases with advancing age [7].

What is the difference between “Adult Onset Growth Hormone Deficiency” (AOGHD) and “Age Related Growth Hormone Deficiency”?

“Deficiency of growth hormone in adults results in a syndrome characterized by decreased muscle mass and exercise capacity, increased visceral fat, impaired quality of life, unfavorable alterations in lipid profile and markers of cardiovascular risk, decrease in bone mass and integrity, and increased mortality.” [15]

Another author states: “….. growth hormone levels decline during advancing years-of-life. These changes ….. are associated with loss of vitality, muscle mass, physical function, together with the occurrence of frailty, central adiposity, cardiovascular complications, and deterioration of mental function.” [16]

So, the reality is that Age Related Growth Hormone Deficiency is identical to the clinical picture (signs & symptoms) seen with Adult Onset Growth Hormone Deficiency. Moreover, the laboratory studies are identical: “the fall in GH secretion is progressive such that by the age of 60 most adults have total 24-hour secretion rates indistinguishable from those of hypopituitary patients with organic lesions in the pituitary gland.” [17]

And here lies the problem for us practitioners of Bio-Identical Hormone Replacement Therapy (B-HRT). Conventional practitioners of the specialty of endocrinology do not accept the idea of B-HRT to treat age-related hormone decline [18].

The endocrinologists promulgate position statements and protocols which they expect other doctors, nurse practitioners, and physician’s Assistants to follow. Everyone has an endocrine problem at one time or another. But there are just not that many practicing endocrinologists, some 5,700 in the US [19] (There are actually fewer endocrinologists than there are hospitals in this country! [20]). Endocrinologists consider themselves the experts in all matters concerning hormones. And they don’t take kindly to upstart practitioners of B-HRT.

Although it is legal for me to prescribe natural hormones, including Armour Thyroid, Testosterone, and Growth Hormone, conventional doctors typically advise against the practice.

So you, as the patient, need to be forewarned about this issue. You need to educate yourself beyond my little articles. You need to ask questions. You need to feel secure that natural hormone replacement therapy provides you with health benefit.

Most patients past menopause (and past the male equivalent, andropause) feel so much better on natural hormones. So, that kind of experience is very convincing.

That is why people take natural hormones: to feel better, but also to obtain health benefit.

But back to Growth Hormone. Most people who take bio-identical hormones stick to Thyroid, Testosterone, Estradiol, Progesterone, DHEA, Melatonin, and Cholecalciferol (D3), but do not take hGH.

First of all, it is expensive; costing, at this writing, $750 to $1,000 per month. (December, 2015)

When I started B-HRT practice in 1997, hGH cost $350 per month.

“Long-term replacement of growth hormone in patients with AOGHD induces favorable effects on Quality of Life as well as bone and metabolic parameters.” [21]

How is hGH administered?

“Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1.” [22] It is given, usually at bedtime, very similar to the way insulin is taken.

Since hGH is a protein, it cannot be taken by mouth.

“For adults, GH replacement therapy should be initiated at a low dose, followed by individualized dose titration while monitoring patients’ clinical status and serum insulin-like growth factor-I (IGF-I) concentrations.” [23] The IGF-1 level is a simple blood test.

The usual adult dose is 0.4 mg per day, but it is a good idea to start with 0.1 or 0.2 mg per day, and titrate the dose upward slowly. This precaution is especially important in the elderly.

What are the side effects?

Elevated blood sugars and insulin resistance can occur for the first 3 to 18 months or so, then normalize. So, people checking their blood sugars can notice a temporary change. Long term studies show no increase in the occurrence of diabetes while taking hGH [23,24].

Swelling ankles, usually mild, can occur. This is due to water retention, usually resolving after decreasing dose and/or lifestyle intervention, like diet and exercise [6,8,15].

The most problematic side effect, in my experience, is joint pain, usually in an elbow, but sometimes a knee, which subsides after reducing the dose. As well, pain in the wrists can occur, mimicking carpal tunnel syndrome. Again, the best way to deal with such pain is to start off with a very low dose, then slow raise it over several weeks time [17].

Occasionally, a patient will be very vulnerable to this consequence and will have generalized joint pain. This miserable situation is usually caused by starting off at the full dose. Again, the fix is to discontinue the hGH, let the joint pain subside, then restart with a very low dose.

I have had some patients tell me that they notice no positive feelings that they would ascribe to taking the hGH. I guess you could call that a sort of side effect. They may be having health benefit, but have not noticed good sensations or emotions.

This may be especially disconcerting for patients who felt more energetic, positive, and upbeat after Armour Thyroid or Testosterone, or in the case of women, Estradiol and Progesterone.

I expect patients to feel free to bring any of their concerns regarding hormone supplementation to me for discussion at any time.

Does hGH cause cancer?

“long-term surveillance of adult Growth Hormone Replacement Therapy has not demonstrated increased cancer risk or mortality.” [15]

However, observational studies of rodents show an increase of cancer and a shorter lifespan in those animals making higher levels of growth hormone. “Mutant mice” making lower levels of growth hormone live longer and have less cancer! [25]

“Extensive epidemiological data exist that also support a link between GH/IGF-1 status and cancer risk.” [26] That is, more Growth Hormone and higher IGF-1’s are linked to cancer and reduced lifespan [27] according to observational (epidemiological) studies conducted since 2009.

Be aware that there is an awful lot of complexity in biological systems. An important issue is that associations determined by observational studies do not prove causation.

What does prove causation are “interventional studies”. Thus, in the case of a hormone, like hGH, effect is demonstrated by administering it to half of a study population. Both halves of the study population are chosen to be as equal as possible in all characteristics. As well, the larger the study population, the better.

“Despite theoretical concerns about the effect of GH on tumor development, this review of various clinical and epidemiological studies demonstrated that there is no clear evidence of a causal relationship between GH treatment in patients with GH deficiency and tumor development.” [28]

Interventional studies conducted over many years have not shown any increase of cancer among patients taking hGH [29]

Ron Rothenberg, MD, professor at the University of California San Diego School of Medicine, flatly states: “the notion that Growth Hormone causes cancer is another myth.” [30]

Does hGH increase lifespan?

There is no proof of that. “A variety of favorable effects of GH replacement have been indicated; however, it has not yet been established fully whether there is a direct effect of GH treatment on reducing mortality.” [28]

“By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice.” [31] Many current observational studies (of mice) in the scientific literature are saying that: “Available evidence indicates that reduced GH signaling is linked to extended longevity.” [32]

Again, opposite opinions are garnered from “associative” vs “interventional studies.”

Does hGH or any B-HRT reverse aging?

Many patients have told me that they feel much better taking natural hormones. They notice increased energy, sociability, and beneficial changes of physical appearance. There are salutary changes of lipids and indicators of inflammation. Patients may feel younger. However, this does not reflect a reversal of a cellular, genetic, or biochemical mechanism which we may postulate as the “aging process” itself.

Does everybody notice benefit from B-HRT?

No. In medicine, we know that no treatment works for everybody.

1. Product Insert, Nutropin AQ® [somatropin (rDNA origin) injection] (2004) http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020522s021,022lbl.pdf
2. Takahashi Y, et al. Growth hormone secretion during sleep. J Clin Invest. 1968 Sep;47(9):2079-90. PMID: 5675428
3 Nindl BC, et al. Growth hormone pulsatility profile characteristics following acute heavy resistance exercise. J Appl Physiol (1985). 2001 Jul;91(1):163-72. PMID: 11408427
4 Weltman A, et al. Endurance training amplifies the pulsatile release of growth hormone: effects of training intensity. J Appl Physiol (1985). 1992 Jun;72(6):2188-96. PMID: 1629072
5 Rothenberg R. Growth Hormone Replacement for Normal Aging. Anti-Aging Therapeutics Vol VIII. American Academy of Anti-Aging Medicine. (2006) ISBN 0-9668937-9-4 http://www.a4m.com/assets/pdf/bookstore/aamt_vol8_ch29_rothenberg.pdf
6 Van Cauter E, et al. Age-Related Changes in Slow Wave Sleep and REM Sleep and Relationship With Growth Hormone and Cortisol Levels in Healthy Men. JAMA. 2000 Aug 16;284(7):861-8. PMID: 10938176
7 Vance ML & Mauras M. Growth Hormone Therapy in Adults and Children. N Engl J Med. 1999 Oct 14;341(16):1206-16. PMID: 10519899
8 Oberbauer, AM. Developmental programming: the role of growth hormone. J Anim Sci Biotechnol. 2015; 6(1): 8. Published online 2015 Feb 12. doi: 10.1186/s40104-015-0001-8 PMCID: PMC4358872
9 Gellerfors P, et al. Characterisation of a secreted form of recombinant derived human growth hormone, expressed in Escherichia coli cells. J Pharm Biomed Anal. 1989;7(2):173-83. PMID: 2488618
10 Rudman D, et al. Effects of human GH in men over 60 years old. N Engl J Med 1990;323:1-6 PMID: 2355952
11 Rudman D, et al. Effects of human growth hormone on body composition in elderly men. Horm Res. 1991;36 Suppl 1:73-81. PMID: 1806490
12 Rouzier, Neal. How to Achieve Healthy Aging. World Link Medical, 1st Ed., 2001. ISBN-13:9780971000711 (Pages 181-207) (2nd edition does not have a chapter on hGH)
13 Bartke A. Pleiotropic effects of growth hormone signaling in aging. Trends Endocrinol Metab. 2011 Nov; 22(11): 437–442. PMCID: PMC4337825
14 Reed ML, et al. Adult Growth Hormone Deficiency – Benefits, Side Effects, and Risks of Growth Hormone Replacement. Front Endocrinol (Lausanne). 2013; 4: 64. Published online 2013 Jun 4. doi:10.3389/fendo.2013.00064 PMCID: PMC3671347
15 Sattler FR. Growth hormone in the aging male. Best Pract Res Clin Endocrinol Metab. 2013 Aug;27(4):541-55. doi: 10.1016/j.beem.2013.05.003. Epub 2013 Jun 18. PMID: 24054930
16 Savine R, Sönksen P. Growth hormone – hormone replacement for the somatopause? Horm Res. 2000;53 Suppl 3:37-41. PMID: 10971102
17 The American Association of Clinical Endocrinologists. CLINICAL PRACTICE GUIDELINES. https://www.aace.com/publications/guidelines
18 Endocrine Clinical Workforce: Supply and Demand Projections. Submitted by: The Lewin Group and The Association of Program Directors in Endocrinology, Diabetes, and Metabolism. For: The Endocrine Society. (June, 2014)
19 US endocrinologist shortage affects access to care, physician satisfaction. Endocrine Today, May 2011 http://www.healio.com/endocrinology/diabetes/news/print/endocrine-today/%7B511d7427-678b-42e0-9b7b-4e374fabc62a%7D/us-endocrinologist-shortage-affects-access-to-care-physician-satisfaction
20 Jørgensen AP, et al. Favorable long-term effects of growth hormone replacement therapy on quality of life, bone metabolism, body composition and lipid levels in patients with adult-onset growth hormone deficiency. Growth Horm IGF Res. 2011 Apr;21(2):69-75. doi: 10.1016/j.ghir.2011.01.001. Epub 2011 Feb 3. PMID: 21295507
21 Gupta V. Adult growth hormone deficiency. Indian J Endocrinol Metab. 2011 Sep; 15(Suppl3): S197–S202. doi: 10.4103/2230-8210.84865 PMCID: PMC3183535
22 Fukuda I, et al. Adult Growth Hormone Deficiency: Current Concepts. Neurol Med Chir (Tokyo). 2014 Aug; 54(8): 599–605. doi: 10.2176/nmc.ra.2014-0088 PMCID: PMC4533495
23 Simpson H, et al. Growth hormone replacement therapy for adults: into the new millennium. Growth Horm IGF Res. 2002 Feb;12(1):1-33. PMID: 12127299
24 Bartke A, et al. Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity. Physiol Rev. 2013 Apr; 93(2): 571–598. doi: 10.1152/physrev.00006.2012 PMCID: PMC3768106
25 Jenkins PJ, et al. Does growth hormone cause cancer? Clin Endocrinol (Oxf). 2006 Feb;64(2):115-21. PMID: 16430706
26 Vladimir N. Anisimov and Andrzej Bartke. The key role of growth hormone — insulin — IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol. 2013 Sep; 87(3): 201–223. doi: 10.1016/j.critrevonc.2013.01.005 PMC4095988
27 Hyun-Wook C, et al. Growth hormone treatment and risk of malignancy. Korean J Pediatr 2015;58(2):41-46. http://dx.doi.org/10.3345/kjp.2015.58.2.41 PMC4357770
28 Jenkins PJ, et al. Does growth hormone cause cancer? Clin Endocrinol (Oxf). 2006 Feb;64(2):115-21. PMID: 16430706
29 Rothenberg R. Hormone Myths Versus Medical Evidence. Anti-Aging Therapeutics Vol XIV. American Academy of Anti-Aging Medicine. (2012) ISBN 978-1-934715-09-3. https://www.worldhealth.net/pdf/Rothenberg_Thera11.pdf
30 Junnila RK, et al. The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol. 2013 Jun; 9(6): 366–376. PMC4074016
31 Bartke A, et al. Links between growth hormone and aging. Endokrynol Pol. 2013; 64(1): 46–52. PMC3647466