Misguided Attacks on HRT
Statute6 21 U.S.C. § 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. 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 commentary4 purported to address the legality of Human Growth Hormone (HGH, GH) treatment by physicians for growth hormone deficient (GHD) patients. The commentary, however, was flawed by a number of incorrect, misplaced references and studies, and multiple basic scientific errors.
In the May-June 2009 issue1 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 Prof. Dr. Imre Zs.-Nagy expresses his opinions on the use of the HGH as an anti-aging medical intervention. Prof. Dr. 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. Prof. Dr. 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.” Dr. Zs.-Nagy submits that: “[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 observes11 that: “For reasons that are not readily apparent, there appears to be a conservative political movement that opposes the use of testosterone in older men. Continuing, Ms. Mollica observes that: “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.”
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HGH
On July 5, 1990, Daniel Rudman, M.D., a pioneer researcher in the use of HGH, and his colleagues at the Medical College of Wisconsin made medical history with an article12 in the New England Journal of Medicine. 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 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 multi-year studies, well beyond the typical 6-12 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 and sarcopenia, fibromyalgia, Crohn's disease, other illnesses, and quality of life issues.15,16,17,18,19,20,21
Low GH22 is associated with decreased longevity in humans, with more than 20 years decreased lifespan with low GH.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 2-3 times increase in mortality.25
Low GH22 and its downstream hormone IGF-1 are associated with poor health and quality of life outcomes. The June 2012 issue26 of The Journals of Gerontology: Series A published a series of articles documenting the clinical benefits of IGF-1. Of note, Higashi et al27 provide “a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging.” Further, Ungvari et al28 cite the “cardiovascular protective effects of insulin-like growth factor (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 that: “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.”
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” reports29 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 to a decrease of 1.8 ml/kg/m among control subjects. 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 to increase of 8 ml/m2 in controls), the American College of Cardiology Foundation/American Heart Association Task Force writes that: “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 suggests that when treating Adult Growth Hormone Deficiency (AGHD, GHD), physicians are treating a documented deficiency disease and not performing off-label treatment as the JAMA commentary4 authors suggest. In fact, HGH deficiency is associated with significantly decreased longevity in human siblings. 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 anti cancer.32 The mechanism is explained by stimulation of anti-cancer 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 to the general population. Jenkins34 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