Thursday, 1 January 2015

10 facts about Human Growth Hormone

Advances in human growth hormone (GH) delivery have been reported recently, offering the anti-aging community, athletes, and physique enthusiasts reason to investigate new advantages and opportunities of this drug/hormone.


1 - Norditropin SimpleXx

 Novo Nordisk A/S is a large pharmaceutical company that already manufactures and markets the once-daily GH product Norditropin SimpleXx. Norditropin has proven to be effective and reliable when used clinically; those who obtain it outside of the legal channels for quality-of-life or performance/physique purposes comment positively.1 Norditropin is typical of pharmaceutical GH. It improves linear growth (height) in treated children, reverses aging-related changes in older subjects, improves body composition, and accelerates healing.


2 - Drug Design

There are a number of challenges in creating a drug that can be inhaled with the intention of absorbing the drug into the bloodstream. First, it cannot be an irritant to the lungs or airways to avoid sneezing it out, or worse yet, induce an asthmatic reaction (bronchoconstriction). Second, the drug cannot cause an unwanted drug response in the lungs/airways (e.g., bleeding). Third, the drug must reach the alveoli (the tiny air sacs where oxygen is exchanged) to be absorbed into the circulation. Fourth, it cannot interfere with gas exchange (oxygen for carbon dioxide).3 There are other considerations, but this gives you an idea of the challenges.


3 - Growth Hormone Delivery: It Doesn’t Come Easy

An inhalable form of GH has proven itself to be an effective substitute for injectable GH in human clinical trials; as yet, this product has not completed FDA approval. Inhalable GH has been shown in adults and children to be bioequivalent in delivering GH, and the drug kinetics— time to peak concentration, clearance, etc.— are similar, as well as the metabolic effect (IGF-1). Both injected and inhaled GH reached peak concentration approximately 2 hours after dosing, and were cleared within 8-10 hours.5 The downside to inhaled GH is that it is inefficient in regard to how much of the drug is absorbed.


4 - Injection

Traditionally, GH is injected subcutaneously (into the fat you can pinch) into the abdomen or thigh.6 This allows GH to disperse relatively quickly and near-completely. The abdomen and thigh are chosen due to the access (people can self-inject into these sites), and circulation is good. Other fat depots do not have adequate blood flow— slowing the release or even “trapping” the drug, rendering it unusable by the body. GH can be injected intramuscularly (IM) to greater effect, but IM injections are more painful and have additional complication risks.7


5 - The New Variation on GH–pGH

A variation on GH has been developed, attaching a long polyethylene glycol chain to the protein structure to prolong its presence in the bloodstream; this is called pegylated GH (pGH).8 Pegylation does not alter the activity of GH, rather it makes the protein bigger so that it is not filtered by the kidneys and pissed away, literally. It may help to think of pegylation as carrier-protein substitute, protecting the hormone and prolonging its presence in the blood. Novo Nordisk A/S, the manufacturer of Norditropin, recently reported the results of studies comparing once-weekly pGH to daily Norditropin, in regard to tolerability and bioequivalence.8 The studies used healthy, non-smoking, non-obese men, aged 20 through 40. None of the subjects showed any injection site reaction, demonstrating the tolerability of pGH. When blood tests were analyzed, pGH was shown to be equivalent to GH on a molar basis within the dose range normally prescribed to adults.


6 - Growth Hormone In Your Body

GH is normally produced in spikes several times through the day and night. It can be stimulated by certain amino acids, exercise, low blood sugar, etc.9 The effects of GH are fairly short-lived, but longer term effects are the result of IGF-1— a secondary protein hormone produced primarily by the liver when stimulated by GH.10 Skeletal muscle is also a significant source of IGF-1, but most of the muscle-derived IGF-1 effects are local (limited to the tissue that produces it).11 Liver-based IGF-1 would be rapidly cleared if it did not bind to a carrier protein complex (IGFBP-3 and ALS).10


7 - Primitive Side Effects Of GH

Early adaptors of GH for bodybuilding and anti-aging suffered a number of side effects, including carpal tunnel syndrome, insulin resistance, type 2 diabetes, facial bone distortion, elongation of hands and feet, organ growth, etc.12 This was due to their inappropriate use of excessive doses, following the treatment routines given to GH-deficient children (around 20 IU/day). This resulted in IGF-1 levels that were higher than the body could accommodate; most GH-related side effects can be managed by keeping IGF-1 values within or near the physiologic (normal) range.


8 - Know The Risks

Of course, as with anabolic steroids and other performance-enhancing drugs, the maximal response requires maximal risk— many are willing to make that trade. IGF-1 induced muscle growth, one of many anabolic effects of growth hormone, is dose related.15 For years, athletes believed that GH increased strength, as well as muscle size. Then research was published stating emphatically that GH-increases in muscle size were either due to fluid retention or increases in non-contractile components in muscle tissue.16 In other words, the muscles may get bigger, but they do not get stronger or perform better.


9 - GH Vs. Test

Now, another study challenges the above claim, showing that in healthy adult men and women who exercise recreationally, GH (6 IU/day) significantly increased Wingate sprint performance— a measure of anaerobic power— by 4 percent compared to a control group that was not treated.17 Men experienced a synergistic increase in the Wingate test to 8.3 percent when testosterone was also administered (250 mgs Sustanon/week) along with GH. Interestingly, while testosterone and GH both increased lean mass, GH did so by increasing extracellular water;testosterone actually increased muscle tissue.


10 - GH benefits fat-loss and reduces muscular deterioration

Many of the benefits of GH relate to metabolic changes affecting energy utilization, or buffering in the muscle to reduce the (lactic) acid-related deterioration in performance. Further, fat loss is obviously beneficial in many sports. It is the chronic elevation of IGF-1 that appears to be related to the anabolic effects of GH, suggesting pGH may have greater effect for those seeking size or power gains.


It is probable that pGH will be approved in a few years; prior to that, it will likely reach self-experimenting bodybuilders or athletes. No additional risk with pGH, relative to current GH formulations, has been noted; yet, the report of delayed clearance, potential for hormone “buildup,” and suppression of endogenous (natural) production seem elevated in instances of abuse (dosing for anabolic versus replacement purposes).



 1. Orme SM, Sebastian JP, et al. Comparison of measures of body composition in a trial of low dose growth hormone replacement therapy. Clin Endocrinol (Oxf), 1992 Nov;37(5):453-9.


2. Desrosiers P, O'Brien F, et al. Patient outcomes in the GHMonitor: the effect of delivery device on compliance and growth. Pediatr Endocrinol Rev, 2005 Feb;2 Suppl 3:327-31.


3. Hohenegger M. Novel and current treatment concepts using pulmonary drug delivery. Curr Pharm Des, 2010;16(22):2484-92.


4. Siekmeier R, Scheuch G. Inhaled insulin--does it become reality? J Physiol Pharmacol, 2008 Dec;59 Suppl 6:81-113.


5. Walvoord EC, de la Peña A, et al. Inhaled growth hormone (GH) compared with subcutaneous GH in children with GH deficiency: pharmacokinetics, pharmacodynamics, and safety. J Clin Endocrinol Metab, 2009 Jun;94(6):2052-9.


6. Beshyah SA, Anyaoku V, et al. The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh. Clin Endocrinol (Oxf), 1991 Nov;35(5):409-12.


7. Keller A, Wu Z, et al. Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration. Eur J Endocrinol, 2007 Jun;156(6):647-53.


8. Rasmussen MH, Bysted BV, et al. Pegylated long-acting human growth hormone is well-tolerated in healthy subjects and possesses a potential once-weekly pharmacokinetic and pharmacodynamic treatment profile. J Clin Endocrinol Metab, 2010 Jul;95(7):3411-7.


9. Devesa J, Lima L, et al. Neuroendocrine control of growth hormone secretion in humans. Trends Endocrinol Metab, 1992 Jul;3(5):175-83.


10. Ohlsson C, Mohan S, et al. The role of liver-derived insulin-like growth factor-1. Endocr Rev, 2009 Aug;30(5):494-535.


11. Frystyk J. Exercise and the growth hormone-insulin-like growth factor axis. Med Sci Sports Exerc, 2010 Jan;42(1):58-66.


12. Mukherjee A, Shalet SM. The value of IGF-1 estimation in adults with GH deficiency. Eur J Endocrinol, 2009 Nov;161 Suppl 1:S33-9.


13. Faje AT, Barkan AL. Basal, but not pulsatile, growth hormone secretion determines the ambient circulating levels of insulin-like growth factor-1. J Clin Endocrinol Metab, 2010 May;95(5):2486-91.


14. Surya S, Horowitz JF, et al. The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects. J Clin Endocrinol Metab, 2009 Aug;94(8):2828-34.


15. Stevens-Lapsley JE, Ye F, et al. Impact of viral mediated IGF-1 gene transfer on skeletal muscle following cast immobilization. Am J Physiol Endocrinol Metab, 2010 Aug 24. [E-pub, ahead of print]


16. Rennie MJ. Claims for the anabolic effects of growth hormone: a case of the emperor's new clothes? Br J Sports Med, 2003 Apr;37(2):100-5.


17. Meinhardt U, Nelson AE, et al. The effects of growth hormone on body composition and physical performance.

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