Читать книгу Anti-Aging Therapeutics Volume XV - A4M American Academy - Страница 13

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 treated with GH has revealed no increase in observed cancer risk.”

Moltich’s³⁵ 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”

With regard for the potential for an increased cancer risk with HGH treatment, peer-reviewed literature suggests the opposite. HGH treatment may up-regulate binding proteins of IGF, specifically IGF-6; this has been noted in studies to prevent many types of cancer, such as prostate, ovarian, brain and endometrial.^{36,37,38,39,40,42} It is also well documented that cancer survivor children who received HGH did not exhibit any increased cancer risks. In fact, there are no peer reviewed long-term clinical studies that document human cancer risks from HGH administration.^38,39,40 To the contrary, cancer mortality and recurrence has been found to be reduced, or survival time increased in cancer patients on HGH. Patients deficient in HGH are reported to have a 400% increase in cancer mortality and a 200% increase of cancer incidence.^41,42 Noted was also a reduction by 50% of cancer risk to patients with long term HGH replacement (60 months).²¹ Additionally, the Growth Hormone Research Society has stated that "Current labeling for GH states that active malignancy is a contraindication. ... There are no data to support this labeling. Current knowledge does not warrant additional warning about cancer risk."⁴³ However, caution should always be exercised in patients with a history of cancer; and HGH therapy is not for every patient.

Ruiz-Torres et al²⁴ completed a study that compared ageing parameters of young (up to 39 years) and old (over 70 years) individuals having similar insulin-like growth factor-1 (IGF-1) blood levels. In follow-up, the researchers studied the decline in IGF-1 levels, comparing its behavior in the first half with that in the second half of adult life. The investigators concluded that: “GH secretion in adulthood plays a determinant role not only for some regressive manifestations, but also for life potential.”

Media reports about the federal law concerning HGH have created unnecessary confusion, and some reports have confused non-medical over-the-counter homeopathic sprays and nutritional products with pharmaceutical-grade, FDA-approved injection medications for AGHD patients. It is A4M's opinion that such misleading journalism incorrectly equates sports and homeopathic nutritional supplements sold through websites with pharmaceutical-grade injectable HGH prescribed for patients with diagnosed AGHD. Such poor presentations of the science and commentary, in A4M's view, have erroneously suggested that the replacement of HGH in aging adults is illegal, and has led to sensationalized headlines. Patients are not given HGH for a diagnosis or treatment of "anti-aging," but for on-label use for AGHD syndrome, a diagnosed disease. It should be noted, that before initiating HGH supplementation, anti-aging physicians first encourage the increase of growth hormone by increasing exercise, enhancing sleep cycles, balancing other hormone deficiencies and decreasing of sugar intake, as evaluated by Gardner, et al.⁴⁴

In a landmark court case⁴⁵, James Forsythe, MD, HMD won a clear and unanimous victory that reaffirmed the right of a physician to prescribe HGH to adults with deficiency conditions, including aging and arthritis. Dr. Forsythe comments⁴⁶ that: “It is a perversion of the law for state licensing boards to mistreat and harass physicians for this legal, just, and appropriate use of this lifesaving medication – human growth hormone.”