Any use of performance-enhancing drugs or hormones banned from professional sports constitutes inappropriate misuse. It is a violation of the A4M Physician Member Code of Ethics to prescribe for the explicit purposes of performance enhancement. The A4M does not endorse or condone the use of any illicit substances for sports cheating. However, the A4M does support the continued availability of such substances to adult patients with objectively assessed hormone deficiencies. Such judicious use of HRT does not equate to a banned drug issue.
A4M's physician cofounders Robert Goldman, MD, PhD, DO, FAASP, chairman, and Ronald Klatz, MD, DO, president, are coauthors of Death In the Locker Room (1984), a first-ever exposé of the illicit use of anabolic steroids in sports, and Grow Young with HGH (1997), a best-selling book that explores the clinical benefits of judicious and appropriate HGH therapy in deficient adults. Death in the Locker Room is widely regarded as the seminal text on the dangers of anabolic and performance-enhancing substances in sports. It was the first book to alert the public and the medical community to such issues, and it subsequently led directly to much of the drug testing, control, and educational programs now in place across a number of professional sports and on the global level.
Statute 21 USC § 333(e), a provision of the Food, Drug, and Cosmetic Act (FDCA), states, in pertinent part, that "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 [FDA] and pursuant to the order of a physician, is guilty of an offense punishable by not more than 5 years in prison."6 We need to take a critical look at the historical context and legislative intent of a law before we interpret it. The law did not originally address HGH. The 1988 law was written and passed regarding anabolic steroids. The legislative history of the statute shows an intent to focus on steroid trafficking to athletes, particularly adolescent athletes, amid increasing reports of amateur and professional sports doping and concerns about the 1988 Summer Olympics (at which, ironically, Canadian sprinter Ben Johnson's positive steroid result ignited a global firestorm).
Goldman served as special adviser and lecturer to the US Drug Enforcement Agency (DEA) Demand Reduction Education Programs nationally, as well as to the US Olympic Committee, spearheading the design of drug policy and testing procedures. In his activities with the DEA, Goldman was directly involved in an advisory capacity with the process that led to the creation of the Anabolic Steroid Control Act of 1990. "The Anabolic Steroid Control Act was never intended to restrict practicing physicians involved in the clinical treatment of hormone deficiency syndromes," comments Goldman, who explains: "Rather, this law was specifically directed to prevent the trafficking of anabolic steroids to athletes."7
The Anabolic Steroid Control Act of 1990 lifted steroids out of the FDCA and into the Controlled Substances Act. Congress was presented with the option of making HGH into a controlled substance, too. However, following expert medical testimony that HGH lacks the adverse psychological and physical effects of steroids, Congress chose not to take such a drastic approach to HGH.8,9 Instead, Congress took the lesser approach of inserting HGH, to replace steroids, in the FDCA law that was written to stop trafficking to cheating athletes. In fact, HGH was inserted as an afterthought, with no penalties mentioned, as editorial comment; there was no intention to criminalize its judicious use in the clinical setting by trained physicians. The focus of lawmakers and Congress has always been to address nonmedical use; that is, improper use by competitive elite athletes, sports enthusiasts, and teenagers. It is A4M's view that the JAMA commentary fails to understand or appreciate such legislative history and legislative purpose.4 A4M is advised that one of the authors of the JAMA commentary stated to United Press International (UPI) in reference to the statute, "They basically put in language that made it crystal clear that it is illegal to use growth hormone as an anti-aging intervention."10 This is a very odd and, A4M believes, an incorrect statement, considering the fact that when the law was written, there were no anti-aging doctors or profession in existence. In fact, the anti-aging medical profession did not even exist until five years after the 1988 statute was enacted. The concept of HGH as an anti-aging drug did not exist until the problem of Rudman's study.12
The Anabolic Steroid Control Act never intended to infringe upon physician freedoms to prescribe hormone therapy when clinically appropriate. It was specifically intended to prevent steroid trafficking in professional sports. Whereas education should have been a primary goal in implementing the Anabolic Steroid Control Act, instead an enforcement environment that granted limitless power unto itself was created. A multimillion dollar industry of drug testing was born and subsequently flourishes.
History is replete with examples of medical pioneers whose innovations and foresight were trivialized, ignored, challenged, or violently opposed by the establishment, only to ultimately become accepted by society at large. Leopold Auenbrugger was ridiculed for percussing and auscultating his patients' chests; Ignaz Semmelweiss's recommendation for doctors to wash their hands before each patient landed him in a mental asylum; and more recently, cardiologists denied Nathan Pritikin's program for dietary modification to modulate cardiovascular risk until after his death. Given time and objective, undeniable evidence, scientific truths are ultimately borne out. In the words of Augenbrugger, "It has always been the fate of those who have illustrated the arts and sciences by their discoveries to be beset by envy, malice, hatred, destruction, and calumny."
Misguided Attacks on HRT
Statute 21 USC Section 333(e), a provision of the Food, Drug, and Cosmetic Act (FDCA), supports the use of hormone replacement in mature, clinically GH-deficient adults as both treatment of a disease and a medically authorized use granted by the FDA.6 Any implication that the statute was intended to target medical hormone replacement by ethical doctors in the new and emerging field of anti-aging medicine is therefore incorrect and misleading.
To obfuscate the truth, critics of the anti-aging medical science offer deliberately misleading claims concerning HRT with the specific and ultimate goal to severely restrict the use of hormone therapy. Most notably, the JAMA commentary purported to address the legality of HGH treatment by physicians for GHD patients.4 The commentary, however, was flawed by a number of incorrect, misplaced references and studies, and multiple basic scientific errors.
In the May–June 2009 issue of the prestigious Archives of Gerontology and Geriatrics, an international journal integrating experimental, clinical, and social studies on aging published by Elsevier, founder and editor-in-chief Zs.-Nagy expresses his opinions on the use of the HGH as an anti-aging medical intervention.1 Zs.-Nagy's editorial points out the main clinical results of HGH replacement therapy (hGHRT) in light of the "membrane hypothesis of aging" (MHA), which he submits as offering a solid basis for the interpretation of the observed beneficial effects of HGH. Zs.-Nagy's profile of the sharp and protracted conflict of views between the gerontological establishment and the A4M exposes a "disregard by certain individuals bearing some of the most prestigious affiliations in the gerontological establishment, for truth, academic integrity, and scientific professionalism." Zs.-Nagy says: "[T]he gerontological elite has … sought to obfuscate the facts of the anti-aging medical movement. I submit that the reason for this is nothing less than an abject fear by the gerontological elite to avert their loss of control, power, prestige, and position in the multi-billion dollar industry of gerontological medicine."
Elite athlete and professional sports/medical writer Monica Mollica observes: "For reasons that are not readily apparent, there appears to be a conservative political movement that opposes the use of testosterone in older men. … The political climate is working against testosterone replacement therapy in older men despite overwhelming scientific data supporting this appropriate pursuit as a strategy to prolong healthy longevity."11
On July 5, 1990, Daniel Rudman, MD, a pioneer researcher in the use of HGH, and his colleagues at the Medical College of Wisconsin made medical history with an article in the New England Journal of Medicine.12 It detailed the first clinical trial of elderly men on HGH therapy, which compared the effects of 6 months of HGH injections on 12 men, aged 61 to 81 years, with an age-matched control group. The result made headlines all over the world. Those taking the hormone injections gained an average of 8.8% in lean body mass and lost 14% fat, without diets or exercise. Their skin became thicker and firmer and the lumbar bones of the spine increased. In other words, HGH had virtually turned their flabby, frail, bodies into those of their sleeker, stronger, younger selves. In language rarely used in conservative medical journals, the researchers wrote: "The effects of 6 months of HGH on lean body mass and adipose-tissue mass were equivalent in magnitude to the changes incurred during 10 to 20 years of aging."
HGH is one of the most studied compounds in medicine, with almost 100,000 journal references currently in PubMed. The majority of these data demonstrate the positive benefits of HGH therapy in multiyear studies, well beyond the typical 6- to 12-month study protocols.13,14
Growth hormone replacement therapy has been shown to improve muscle strength and mobility, cognitive function, cardiovascular disease, osteoporosis, immune function, body composition, obesity, sarcopenia, fibromyalgia, Crohn's disease, other illnesses, and quality-of-life issues.15–21
Low GH is associated with decreased longevity in humans, with more than 20 years decreased lifespan with low GH.22,23 Older men with higher IGF-1 do not show the same decrease in lean body mass and increase in fat mass. "GH determines life's potential."24
Childhood or adult GH deficiency is associated with 2 to 3 times increase in mortality.25
Low GH and its downstream hormone IGF-1 are associated with poor health and quality of life outcomes.22 The June 2012 issue of the Journals of Gerontology: Series A published a series of articles documenting the clinical benefits of insulin-like growth factor (IGF-1).26 Of note, Higashi et al. provide "a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging."27 Further, Ungvari et al. cite the "cardiovascular protective effects of [IGF-1]" to "[provide] a landscape of molecular mechanisms involved in cardiovascular alterations in patients and animal models with … adult-onset IGF-1 deficiency," submitting: "Microvascular protection conferred by endocrine and paracrine IGF-1 signaling" suggest "its implications for the pathophysiology of cardiac failure and vascular cognitive impairment, and the role of impaired cellular stress resistance in cardiovascular aging."28
The "2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines" reports that treating GH deficiency in patients with chronic heart failure beneficially affects the primary endpoint of peak oxygen consumption, which showed "remarkable" increases of 7.1 ml/kg/m in GH-treated patients, as compared with a decrease of 1.8 ml/kg/m among control subjects.29 In that left ejection fraction rose by 10% in the GH- treated patients (declined 2% in controls), with a greater effect on left ventricular and systolic volume index of −22 ml/m2 (as compared with increase of 8 ml/m2 in controls), the American College of Cardiology Foundation/American Heart Association Task Force writes: "The improvements … are consolidated predictors of survival." Notably, there were no major adverse events among the GH-treated patients.
As stated by Savine: "If mean IGF-1 of 300 is mean normal for 20–30 year olds, almost all men and women over the age of 40 have an IGF-1 deficit."30 Most patients beyond age 60 have total 24 hour HGH secretion rates indistinguishable from those of hypopituitary patients with organic pituitary gland lesions.30 Therefore the A4M submits that the empirical data suggest that when treating adult GHD (AGHD), physicians are treating a documented deficiency disease and not performing off-label treatment as the JAMA commentary authors suggest. In fact, HGH deficiency is associated with significantly decreased longevity in human siblings.4 Longevity and healthy aging are directly related to GH/IGF-1 levels.31 As Savine points out, "Life without GH is poor in quantity and quality."30
When AGHD is treated with GH, there are usually increases in GH, IGF-1 and IGF binding protein 3 (IGFBP-3), which all have a role in clinical results. Although IGF-1 is pro-mitotic and taken out of context could promote cancer, IGFBP-3 is anticancer.32 The mechanism is explained by stimulation of anticancer gene p53. Teenagers with the highest GH and IGF-1 have low rates of cancer. When treating with GH, a balance is produced between IGF-1 and IGFBP-3.33 A central question in GHRT is, does GHRT increase the risk of cancer? Multiple studies and reviews have concluded that there is no increase in cancer risk compared with the general population. Jenkins review is aptly titled "Does Growth Hormone Cause Cancer?" and provides the conclusion:
Extensive studies of the outcome of GH replacement in childhood cancer survivors show no evidence of an excess of de novo cancers, and more recent surveillance of children and adults treated with GH has revealed no increase in observed cancer risk.34
Moltich's review has similar conclusions:
Although there has been some concern about an increased risk of cancer, reviews of existing, well-maintained databases of treated patients have shown this theoretical risk to be nonexistent.35