HGH controversies

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Controversies regarding the use of human growth hormone (HGH) as treatment method have centered on the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. Most of these controversies fall into two categories:[ citation needed ]

Contents

  1. Claims of exaggerated, misleading, or unfounded assertions that growth hormone treatment safely and effectively slows or reverses the effects of aging.
  2. The sale of products that fraudulently or misleadingly purport to be growth hormone or to increase the user's own secretion of natural human growth hormone to a beneficial degree.

History

A study was published in The New England Journal of Medicine in 1990 by Rudman et al., which showed fat loss, muscle mass increase and maintenance of healthy skin from the administration of growth hormone in twelve elderly men. [1] Despite the fact the authors at no time claimed that GH had reversed the aging process itself, their results were misinterpreted as indicating that GH is an effective anti-aging agent. [2] [3] [4] This study, and others, has led to organizations such as the controversial American Academy of Anti-Aging Medicine promoting the use of this hormone as an "anti-aging agent". [5]

Additionally, companies selling dietary supplements have websites selling products that claim to be linked to GH in the advertising text, with medical-sounding names described as "HGH Releasers". Typical ingredients include amino acids, minerals, vitamins, and/or herbal extracts, the combination of which are described as causing the body to make more GH with corresponding beneficial effects. In the United States, because these products are marketed as dietary supplements it is illegal for them to contain GH, which is a drug. Also, under United States law, products sold as dietary supplements cannot have claims that the supplement treats or prevents any disease or condition, and the advertising material must contain a statement that the health claims are not approved by the FDA. The FTC and the FDA do enforce the law when they become aware of violations. [6]

As a result of the reactions to the 1990 article and its frequent citation by proponents of HGH as any anti-aging agent, in 2003 the NEJM published two articles that came out strongly and clearly stating that there was insufficient medical and scientific evidence to support use of HGH as anti-aging drug. One article was written by the Journal's then-current editor in chief, Jeffrey M. Drazen, M.D. and was entitled, "Inappropriate Advertising of Dietary Supplements". [7] It focused mostly on the advertising of dietary supplements. The other article was written by the editor-in-chief at the time the 1990 article was published, Mary Lee Vance, M.D., and was entitled, "Can Growth Hormone Prevent Aging?"; it focused more on the medical issues around whether there was sufficient evidence to use HGH as an anti-aging agent. [8]

Research

There has never been an adequately large randomized controlled trial to prove definitively that HGH provides significant anti-aging benefits and that there are no significant adverse drug reactions; there have been many small studies which are described below. [8]

Some scientific articles have demonstrated that HGH supplementation does not significantly increase muscle strength or aerobic exercise capacity in healthy individuals. [9] While it is possible that there are some advantages, such as an increase in lean body mass, it is also evident that benefits are being exaggerated by some for commercial gain and ineffective products are being sold to unsuspecting consumers. [10]

Some recent small clinical studies have shown that low-dose GH treatment for elderly patients with GH deficiency changes the body composition by increasing muscle mass, decreasing fat mass, increasing bone density and muscle strength, improves cardiovascular parameters (i.e. decrease of LDL cholesterol), and affects the quality of life without significant side effects. [11] [12] [13] It must be emphasized that these studies were small—only tens of patients—and the results were therefore stated tentatively; in the words of one of the cited sources: "Clearly more studies are needed before GH replacement for the elderly becomes established. Safety issues will require close scrutiny, but the data available so far are sufficiently positive to undertake large multicentre, placebo-controlled trials, particularly looking at endpoints associated with prevention of frailty and loss of independence." [13]

Side-effects of high doses and long-term use

Some of the side effects reportedly seen in previously healthy mature patients after taking high HGH doses include:

Chronic use of HGH is not well studied. However, in Europe a study called "SAGhE" was undertaken to study these long-term effects of HGH in children. [16] It found that persons with certain kinds of short stature (idiopathic growth hormone deficiency and idiopathic or gestational short stature) who were treated with recombinant human growth hormone during childhood and who were followed over a long period of time, were at a small increased risk of death when compared to individuals in the general population of France. The FDA issued a Safety Alert reporting this result. [17]

Law

In 1990, the US Congress passed an omnibus crime bill, the Crime Control Act of 1990, that amended the Federal Food, Drug, and Cosmetic Act, that classified anabolic steroids as controlled substances and added a new section [18] which reads:

Prohibited distribution of human growth hormone.

(1) Except as provided in paragraph (2), whoever knowingly distributes, or possesses with intent to distribute, human growth hormone for any use in humans other than the treatment of a disease or other recognized medical condition, where such use has been authorized by the Secretary of Health and Human Services under section 355 of this title and pursuant to the order of a physician, is guilty of an offense punishable by not more than 5 years in prison, such fines as are authorized by title 18, or both.
(2) Whoever commits any offense set forth in paragraph (1) and such offense involves an individual under 18 years of age is punishable by not more than 10 years imprisonment, such fines as are authorized by title 18, or both.
(3) Any conviction for a violation of paragraphs (1) and (2) of this subsection shall be considered a felony violation of the Controlled Substances Act [21 U.S.C. 801 et seq.] for the purposes of forfeiture under section 413 of such Act [21 U.S.C. 853].
(4) As used in this subsection the term “human growth hormone” means somatrem, somatropin, or an analogue of either of them.

(5) The Drug Enforcement Administration is authorized to investigate offenses punishable by this subsection. [19] [20]

This section has been taken by some, most notably [18] [21] the authors of a commentary article published in the Journal of the American Medical Association in 2005, as meaning that prescribing HGH off-label may be considered illegal. "Physicians and other health care professionals should be aware that current law explicitly prohibits the distribution of GH except for clearly and narrowly defined indications. Distribution for other uses, or off-label use, such as for antiaging, age-related conditions, and enhancing athletic performance, are illegal. Although GH is not a schedule III drug, section 303 [333] f(5) of the FDCA clearly provides the Drug Enforcement Administration with the responsibility of enforcing the laws governing human GH. Given the clinical concerns and the legal issues involved, we believe that physicians or other persons who currently market, distribute, or administer GH to their patients for any reason other than the well-defined approved (ie, legal) uses of the drug, should not do so." [22]

The Drug Enforcement Administration of the US Department of Justice considers off-label prescribing of HGH to be illegal, and to be a key path for illicit distribution of HGH. [23] The FDA, as recently as 2012, has issued alerts stating that "FDA-approved HGH can be legally prescribed for a limited number of conditions." [24] The FDA and the Department of Justice have shut down companies and compounding pharmacies that have marketed HGH for off-label purposes – especially for bodybuilding and anti-aging uses. [25] [26] And some articles in the popular press, such as those criticizing the pharmaceutical industry for marketing drugs for off-label use (which is clearly illegal) have made strong statements about whether doctors can prescribe HGH off-label: "Unlike other prescription drugs, HGH may be prescribed only for specific uses. U.S. sales are limited by law to treat a rare growth defect in children and a handful of uncommon conditions like short bowel syndrome or Prader-Willi syndrome, a congenital disease that causes reduced muscle tone and a lack of hormones in sex glands." [27] [28]

At the same time, anti-aging clinics where doctors prescribe, administer, and sell HGH to people are big business. [27] [29] In a 2012 article in Vanity Fair, when asked how HGH prescriptions far exceed the number of adult patients far exceeds the estimates for HGH-deficiency, Dr. Dragos Roman, who leads a team at the FDA that reviews drugs in endocrinology, said "The F.D.A. doesn't regulate off-label uses of H.G.H. Sometimes it's used appropriately. Sometimes it's not." [29]

See also

Related Research Articles

<span class="mw-page-title-main">Growth hormone</span> Peptide hormone, that stimulates growth

Growth hormone (GH) or somatotropin, also known as human growth hormone in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of Insulin-like growth factor 1 (IGF-1) and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

<span class="mw-page-title-main">Prescription drug</span> Medication legally requiring a medical prescription before it can be dispensed

A prescription drug is a pharmaceutical drug that is permitted to be dispensed only to those with a medical prescription. In contrast, over-the-counter drugs can be obtained without a prescription. The reason for this difference in substance control is the potential scope of misuse, from drug abuse to practicing medicine without a license and without sufficient education. Different jurisdictions have different definitions of what constitutes a prescription drug.

<span class="mw-page-title-main">Growth hormone deficiency</span> Medical condition

Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also present low blood sugar or a small penis size. In adults there may be decreased muscle mass, high cholesterol levels, or poor bone density.

Growth hormone therapy refers to the use of growth hormone (GH) as a prescription medication—it is one form of hormone therapy. Growth hormone is a peptide hormone secreted by the pituitary gland that stimulates growth and cell reproduction. In the past, growth hormone was extracted from human pituitary glands. Growth hormone is now produced by recombinant DNA technology and is prescribed for a variety of reasons. GH therapy has been a focus of social and ethical controversies for 50 years.

<span class="mw-page-title-main">Sibutramine</span> Appetite suppressant

Sibutramine, formerly sold under the brand name Meridia among others, is an appetite suppressant which has been discontinued in many countries. It works as a serotonin–norepinephrine reuptake inhibitor similar to a tricyclic antidepressant. Until 2010, it was widely marketed and prescribed as an adjunct in the treatment of obesity along with diet and exercise. It has been associated with increased cardiovascular diseases and strokes and has been withdrawn from the market in 2010 in several countries and regions including Australia, Canada, China, the European Union, Hong Kong, India, Mexico, New Zealand, the Philippines, Thailand, the United Kingdom, and the United States. However, the drug remains available in some countries.

Late-onset hypogonadism (LOH) or testosterone deficiency syndrome (TDS) is a condition in older men characterized by measurably low testosterone levels and clinical symptoms mostly of a sexual nature, including decreased desire for mating, fewer spontaneous erections, and erectile dysfunction. It is the result of a gradual drop in testosterone; a steady decline in testosterone levels of about 1% per year can happen and is well documented in both men and women.

The American Academy of Anti-Aging Medicine (A4M) is a United States 501(c)(3) nonprofit organization that promotes the field of anti-aging medicine, and the organization trains and certifies physicians in this specialty. As of 2011, approximately 26,000 practitioners had been given A4M certificates. The field of anti-aging medicine is not recognized by established medical organizations, such as the American Board of Medical Specialties (ABMS) and the American Medical Association (AMA). The academy's activities include lobbying and public relations. The A4M was founded in 1993 by osteopathic physicians Robert M. Goldman and Ronald Klatz, and as of 2013 claimed 26,000 members from 120 countries.

Saizen is a commercial preparation of synthetic somatropin. Manufactured by Merck Serono, Saizen is produced by recombinant DNA technology from a mammalian cell line that was modified by the addition of the human GH gene, resulting in an identical 191-amino acid sequence and structure.

Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of hormone therapy in which androgens, often testosterone, are supplemented or replaced. It typically involves the administration of testosterone through injections, skin creams, patches, gels, pills, or subcutaneous pellets. ART is often prescribed to counter the effects of male hypogonadism.

<span class="mw-page-title-main">Laron syndrome</span> Medical condition

Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 production in response to growth hormone. It is usually caused by inherited growth hormone receptor (GHR) mutations.

Mecasermin rinfabate, also known as rhIGF-1/rhIGFBP-3, is a drug consisting of recombinant human insulin-like growth factor 1 (IGF-1) and recombinant human insulin-like growth factor binding protein-3 (IGFBP-3) which is used for the treatment of amyotrophic lateral sclerosis.

Growth hormones in sports refers to the use of growth hormones for athletic enhancement, as opposed to growth hormone treatment for medical therapy. Human Growth Hormone is a prescription medication in the US, meaning that its distribution and use without a prescription is illegal. There is limited evidence that GH doping improves athletic performance, although the perception that it does is common in the sporting community. Potential side effects of long term GH doping could mirror the symptoms found in sufferers of acromegaly, a disease in which the anterior pituitary gland produces excess growth hormone. These symptoms include swelling of the hands and feet, joint pain, fluid retention, and excessive sweating.

Regorafenib, sold under the brand name Stivarga among others, is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK). Regorafenib shows anti-angiogenic activity due to its dual targeted VEGFR2-TIE2 tyrosine kinase inhibition. Since 2009 it was studied as a potential treatment option in multiple tumor types. By 2015 it had two US approvals for advanced cancers.

The anti-aging movement is a social movement devoted to eliminating or reversing aging, or reducing the effects of it. A substantial portion of the attention of the movement is on the possibilities for life extension, but there is also interest in techniques such as cosmetic surgery which ameliorate the effects of aging rather than delay or defeat it.

The Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) is a disease specific patient-reported outcome measure which measures the effect growth hormone deficiency has on adult patients. The score of the QoL-AGHDA is used to determine the extent to which growth hormone deficiency has affected the patient’s quality of life, and what treatment can then be administered. A high score on the QoL-AGHDA indicates that the patient suffers from many symptoms and therefore has a lower quality of life.

<span class="mw-page-title-main">Macimorelin</span> Chemical compound

Macimorelin (INN) – or Macrilen – is a drug that was developed by Æterna Zentaris for use in the diagnosis of adult growth hormone deficiency. Macimorelin acetate, the salt formulation, is a synthetic growth hormone secretagogue receptor agonist. It is a growth hormone secretagogue receptor agonist, causing release of growth hormone from the pituitary gland. Macimorelin acetate is described chemically as D-Tryptophanamide, 2-methylalanyl-N-[(1R)-1-(formylamino)-2-(1H-indol-3-yl)ethyl]-acetate.

Metreleptin, sold under the brand name Myalept among others, is a synthetic analog of the hormone leptin used to treat various forms of dyslipidemia. It has been approved in Japan for metabolic disorders including lipodystrophy and in the United States as replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy.

<span class="mw-page-title-main">Alpelisib</span> Chemical compound

Alpelisib, sold under the brand name Piqray among others, is a medication used to treat certain types of breast cancer. It is used together with fulvestrant. It is taken by mouth. It is marketed by Novartis.

Somapacitan, sold under the brand name Sogroya, is a growth hormone medication. Somapacitan is a human growth hormone analog. Somapacitan-beco is produced in Escherichia coli by recombinant DNA technology.

Lonapegsomatropin, sold under the brand name Skytrofa, is a human growth hormone used for the treatment of growth hormone deficiency. Lonapegsomatropin is a prodrug of somatropin.

References

  1. ↑ Rudman D, Feller AG, Nagraj HS, et al. (July 1990). "Effects of human growth hormone in men over 60 years old". The New England Journal of Medicine. 323 (1): 1–6. doi: 10.1056/NEJM199007053230101 . PMID   2355952.
  2. ↑ Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, Hoffman AR (January 2007). "Systematic review: the safety and efficacy of growth hormone in the healthy elderly". Ann. Intern. Med. 146 (2): 104–15. doi:10.7326/0003-4819-146-2-200701160-00005. PMID   17227934. S2CID   27279712.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ↑ "No proof that growth hormone therapy makes you live longer, study finds". PhysOrg.com. 2007-01-16. Retrieved 2009-03-16.
  4. ↑ "Growth Hormone Schemes and Scams". www.quackwatch.org. 5 June 2016.
  5. ↑ Kuczynski, Alex (1998-04-12). "Anti-Aging Potion or Poison?". New York Times.
  6. ↑ Singleton ER (2010-06-04). "Atlas Operations, Inc". Warning Letter. U.S. Food and Drug Administration. Retrieved 2011-08-28.
  7. ↑ Drazen, Jeffrey M. (2003). "Inappropriate Advertising of Dietary Supplements". New England Journal of Medicine. 348 (9): 777–778. doi: 10.1056/NEJMp030021 . PMID   12606730.
  8. 1 2 Vance, Mary Lee (2003). "Can Growth Hormone Prevent Aging?". New England Journal of Medicine. 348 (9): 779–780. doi: 10.1056/NEJMp020186 . PMID   12606731.
  9. ↑ H Liu; DM Bravata; I Olkin; et al. (May 2008). "Systematic review: the effects of growth hormone on athletic performance". Annals of Internal Medicine. 148 (10): 747–58. doi:10.7326/0003-4819-148-10-200805200-00215. PMID   18347346. S2CID   19263307.
  10. ↑ "Anti-Aging Products". Consumer Information. Federal Trade Commission. June 2005. Retrieved 2017-06-18.
  11. ↑ Alexopoulou O, Abs R, Maiter D (2010). "Treatment of adult growth hormone deficiency: who, why and how? A review". Acta Clinica Belgica. 65 (1): 13–22. doi:10.1179/acb.2010.002. PMID   20373593. S2CID   24874132.
  12. ↑ Ahmad AM, Hopkins MT, Thomas J, Ibrahim H, Fraser WD, Vora JP (June 2001). "Body composition and quality of life in adults with growth hormone deficiency; effects of low-dose growth hormone replacement". Clinical Endocrinology. 54 (6): 709–17. doi: 10.1046/j.1365-2265.2001.01275.x . PMID   11422104. S2CID   12681649.
  13. 1 2 Savine R, Sönksen P (2000). "Growth hormone - hormone replacement for the somatopause?". Hormone Research. 53 (Suppl 3): 37–41. doi:10.1159/000023531. PMID   10971102. S2CID   30263334.
  14. 1 2 3 4 5 Liu, H.; et al. (2007). The safety and efficacy of growth hormone in the healthy elderly: A systematic review. Annals of Internal Medicine. PMID   17227934.
  15. ↑ Noto, Richard; Maneatis, Thomas; Frane, James; Alexander, Kimberly; Lippe, Barbara; Davis, D. Aaron (2011-01-01). "Intracranial hypertension in pediatric patients treated with recombinant human growth hormone: data from 25 years of the Genentech National Cooperative Growth Study". Journal of Pediatric Endocrinology and Metabolism. 24 (9–10): 627–31. doi: 10.1515/JPEM.2011.319 . ISSN   2191-0251. PMID   22145447. S2CID   3799701.
  16. ↑ "SAGhE : Santé Adulte Gh Enfant". Archived from the original on 2012-04-26. Retrieved 2011-12-31.
  17. ↑ "FDA Drug Safety Communication: Safety review update of Recombinant Human Growth Hormone (somatropin) and possible increased risk of death". FDA. 28 June 2019.
  18. 1 2 Ryan Cronin. (2008) Bureaucrats vs. Physicians: Have Doctors Been Stripped of Their Power to Determine the Proper Use of Human Growth Hormone in Treating Adult Disease? Archived 2012-01-19 at the Wayback Machine Journal of Law & Policy 27 pp 191–217
  19. ↑ "21 U.S. Code § 333 – Penalties". LII / Legal Information Institute.
  20. ↑ Note: this provision was originally made section (e) but was made section (f) in 1993. see US Department of Justice Civil Resource Manual for Prosecutors, "Human Growth Hormone/Steroids Statutory Overview"
  21. ↑ News Author: Laurie Barclay, MD, CME Author: Désirée Lie, MD, MSEd for Medscape. October 28, 2005 Growth Hormone Deemed Illegal for Off-Label Antiaging Use
  22. ↑ Perls; et al. (2005). "Antiaging": Clinical and Legal Issues". JAMA. 294 (16): 2086–90. doi:10.1001/jama.294.16.2086. PMID   16249424.
  23. ↑ DEA, US Department of Justice. DEA: Genotropin Quote: "The illicit distribution of hGH occurs as the result of physicians illegally prescribing it for off-label uses, and for the treatment of FDA-approved medical conditions without examination and supervision"
  24. ↑ FDA. December 14, 2012. Import Alert 66–71: Detention Without Physical Examination of Human Growth Hormone (HGH), Also Known As Somatropin
  25. ↑ Example warning letter to a compounding pharmacy: FDA. June 7, 2004. FDA Warning Letter. File #14-NWJ-14 to Drugs Are Us, Inc. DBA Hopewell Pharmacy
  26. ↑ US Department of Justice. US Department of Justice Civil Resource Manual for Prosecutors, "Human Growth Hormone/Steroids Statutory Overview"
  27. 1 2 David Caruso and Jeff Donn for the Associated Press. December 21, 2012 AP Impact: Big Pharma Cashes in on HGH Abuse
  28. ↑ Dr. Gregory Lindson for HRTGuru corp. July 21, 2018 Is HGH illegal?
  29. 1 2 Ned Zeman for Vanity Fair. March 2012 Hollywood's Vial Bodies
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