What is Anti-Aging Medicine?

Do you have a teenager at home? Many parents describe their teenager as entering the prime of their life. Physically the teen is maturing, becoming leaner and performing better than ever. Memory and mental capacity are approaching their peek.

Such is not the case with my teenager at home. He's slowing down, his arthritis is getting worse, his fur is becoming more coarse, his nose is drier....

OK, so now you've probably figured out my "teen" is my dog. Your vibrant teen and my failing dog are the same age, yet many would note that they haven't aged in the same manner. The point that can be made is this: "aging" is a lot more complex than the simple passage of time.

To a certain extent, when your doctor treats your high blood pressure, checks your cholesterol, and treats your illnesses, he or she is practicing "anti-aging medicine." From the time doctors start medical school, we are trained to focus on helping patients live longer. The meaning of the term "anti-aging medicine" as it is more recently understood can be reflected in an anti-aging credo: live long, live strong.

Anti-aging medicine can encompass many different modalities. Antioxidants, low glycemic diets, weight resistance training can all be a part of an anti-aging regimen, but at the forefront of anti-aging medicine is the evaluation and treatment with hormones such as thyroid, testosterone, estrogen, DHEA, and growth hormone.

It is a medical fact that the decline our bodies go through as the years pass mirror the decline in the concentrations of various hormones in our body. The big questions are these: how much do the decline in these hormones have on what we attribute to "natural aging," and can increasing these hormones back to concentrations we had when we were younger and healthier have a positive inpact on the quality and quantity of our lives?

Let's focus on one of these hormones -- growth hormone. Most people normally think of growth hormone as important only when kids are growing, but it is a hormone that is constantly made and secreted by our pituitary gland throughout our lives. Growth hormone stimulates the release of another hormone, insulin-like growth factor-1 (IGF-1). It is actually through the release of this hormone that growth hormone exerts it's many beneficial actions on the body: decreased body fat, increased muscle mass, decreased LDL (bad) cholesterol, increased skin thickness, increased bone density.

Doctors usually don't measure growth hormone levels in the body because the hormone is usually released in short pulses and lasts a very short time in the body. Doctors measure IGF-1 levels as a fair estimate of growth hormone levels because growth hormone stimulates it, IGF-1 does essentially the same functions, and lasts longer in the body.

Typically, children have IGF-1 levels of around 200. During the teen growth spurt, the levels increase to about 400-1,000, then return to the upper 200s at age 21. IGF-1 levels then steadily decline about 14% per decade. By the age of 60, most adults have growth hormone secretion rates indistinguishable from those younger patients with lesions or malfunctions of pituitary gland (Hormone Research, 2000). On the other side of the coin, there are some people who unfortunately develop a pituitary tumor that causes them to be giants, a condition called acromegaly. These people typically have IGF-1 levels of 3,000 - 6,000.

In 1990, a study published in the New England Journal of Medicine focused on what would happen if average healthy men aged 61-81 were given shots of supplemental growth hormone to give them IGF-1 levels equivalent to that of young men. The results showed that in only 6 months, fat decreased, muscle mass increased, skin thickness increased, and bone density increased.

Other studies have shown that giving supplemental shots of growth hormone can improve memory (Neuropsychobiology, 1998), cognition (Psychoneuroendocrinology, Jan 2004), lower LDL cholesterol, increase cartilage thickness, and improve aerobic capacity (Hormone Research, 2000). To date, we have found no permanent serious side effects with growth hormone supplementation. Studies have also shown that tumors do not grow following treatment with human growth hormone (Anticancer Drugs, Sep 2000). However, there has not been enough time to prove that giving supplemental growth hormone can make people live longer, and there is no guarantee that nothing bad will ever be discovered about growth hormone.

A simple search on the internet for "anti-aging" or "growth hormone" will yield thousands of links to companies that want to sell you something in hopes that it will make you feel 21 again. In general, the more sensational the claim, the more likely you are being misled. Try to only use information from someone who is not trying to sell you something, and from a source that has well organized, placebo controlled studies to support claims (PubMed).

Back in the 1950s, it was theorized that lowering ones cholesterol may lead to a decreased incidence of heart attacks, but it wasn't until 40 years later in 1994 that this was proven. Today millions of people take medications to lower our cholesterol to help us have squeaky clean arteries that can help us live longer. But look around you to see how the average 90 year old is living. Are you looking forward to this quality of life? Will the added years you gain be lived in happiness or in misery? What can we do to not only live long, but live strong? This is the essence of anti-aging medicine.

OFFICIAL A4M RESPONSE TO JAMA COMMENTARY ON
GROWTH HORMONE

Official Response from The American Academy of Anti-Aging Medicine (A4M) to:
Journal of the American Medical Association (JAMA) commentary published October 26, 2005 and titled 'Provision or Distribution of Growth Hormone for "Anti-Aging": Clinical and Legal Issues'

A recently published JAMA Commentary purported to address the legality of Human Growth Hormone (hGH, GH) treatment by physicians for growth hormone deficient (GHD) patients. The commentary was filled with incorrect, misplaced references and studies, and multiple basic scientific errors, in an apparent attempt to damage the Anti-Aging medical profession and the physicians practicing solid, evidence-based medical healthcare focused on improving patients' quality of life. The authors selected self-serving studies, in which they failed to qualify the conclusions in an effort to bolster their disinformation campaign. They wrongfully intermingled internet sales of homeopathic pseudo "GH" sprays, amino acids, and sports nutritional over the counter products in order to inflate their misleading claims suggesting an illegal diversion of hGH by physicians and pharmacies, implying a black market in FDA approved prescription injectable hGH for hormone replacement treatments by anti-aging physicians where none exists.1, 2

After diligent review by international scientific and legal teams, herein is the official response from the American Academy of Anti-Aging Medicine (A4M). Numerous medical specialists are also directing their independent responses to JAMA as Letters to the Editor, as well as conducting press release responses. Biased, agenda based, inaccurately misrepresented data cannot be left unchallenged and is a threat to both patients and physicians who believe in freedom of choice in healthcare.

Despite the fact that this paper passed peer review for such a prestigious publication as JAMA, we herewith present a full, accurate, and factual rebuttal that is not possible within the space constraints of a JAMA Letter to the Editor. This data will be utilized by legal teams, along with assistance from the medical insurance industry, to protect physicians against untoward, unfair and unjustified persecution by state medical boards and other regulatory agencies and should be utilized along with other materials now being prepared to protect your right to practice advanced medicine for the benefit of your patients.

The authors of the JAMA commentary state that the positive effects of hGH "may be shortlived" and state "to our knowledge, no studies have assessed long-term efficacy or safety of GH administration as an anti-aging intervention in humans." There is ample peer review research in the medical literature demonstrating the positive benefits of this pharmaceutical agent in multi-year studies, well beyond the typical 6-12 month study protocols.3,4 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.5,6,7,8,9,10,11

The Blackman study,12 which the authors use to bolster their side effect theories, has already been called to task in JAMA published rebuttals: the dosages (which are misrepresented by the JAMA commentary authors) far exceed the proper and usual dose commonly employed by physicians in clinical practice -- with side effects noted on the order of 1 to 2%.13,14 Recent Blackman studies now cite the benefits of low dose HGH without mention of side effects seen with the supra-physiologic dosages.14

The side effect profile does not apply to clinical treatment where low doses are used initially and doses are slowly ramped up and decreased if side effects occur. Significant side effects are rarely seen in clinical practice. Also when the same total dose is divided daily over a week-long period (instead of administering 3 days a week) side effects are diminished or absent. If side effects do occur, it has been clinically demonstrated that they disappear with cessation of treatment.

As stated by Savine in the same issue of JAMA in which the subject Commentary appeared: "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."15 Most patients beyond age 60 have total 24 hour hGH secretion rates indistinguishable from those of hypopituitary patients with organic pituitary gland lesions.16Therefore when treating Adult Growth Hormone Deficiency (AGHD, GHD), 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. Longevity and healthy aging are directly related to GH/IGF-1 levels.16

Human Growth Hormone (hGH) has been reported to increase muscle strength in GH-deficient adults17, functional breathing capacity in patients with chronic bronchitis18, and resting metabolic rate.19Human Growth Hormone (hGH) has also been reported to be useful in Wasting Syndromes (including AIDS) and may also be neuro-protective,20despite the JAMA commentary authors claiming otherwise.

In spite of the JAMA commentary authors' statements regarding an increased cancer risk with hGH treatment, they failed to report supportive data. Human Growth Hormone (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.20,21,22,23,24,25,26It 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.22,23,24Contrarily, 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.25,26Noted was also a reduction by 50% of cancer risk to patients with long term hGH replacement (60 months).20Additionally, 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."27 However, caution should always be exercised in patients with a history of cancer; and hGH therapy is not for every patient.

Treatment of AGHD in elderly patients may not require diagnosis of specific clinical factors associated with a low IGF-1. Symptoms of AGHD and aging, such as increased body fat, decreased lean body mass, decreased bone density, impaired cardiac function,3,4,5,28,29,30and other parameters, are part of the diagnosis and may be sufficient for a clinical treatment trial of hGH in adults with low IGF-1.   Diagnosis of AGHD is the responsibility of the physician and is determined as described in the following paragraph.

To determine if a patient is growth hormone deficient, IGF-1 is a commonly used standard adequate marker for treatment.31,32,33 Contrary to the proposition by the JAMA commentary authors, determination of AGHD may be based on IGF-1 and its deficiency can lead to a distinct syndrome with potentially serious health issues.34 We strongly disagree with the JAMA authors and feel that IGF-1 is a legitimate gauge of AGHD in adults. Tens of thousands of physicians depend upon Quest Diagnostic Laboratories, one of the nation's largest and leading clinical testing facilities, whose protocol states "Although IGF-1 may not be a perfect test for the diagnosis of adult GHD, it may be sufficiently informative in many cases to warrant using it on a routine basis and has a role in monitoring the safety of adult patients who are on HGH treatment."35 Testing a patient's IGF-1 is important for proper diagnosis, optimization and titration of GH administration, i.e., "titrate the dose gradually until serum IGF-1 is between the median and upper end of the age-related reference range."36 There are many studies that support the benefits of treating AGHD.37,38,39

There is a distinct difference between specific species of mouse animal models that skew data, and of course interspecies differences between humans and animal models. Certain animal IGFs have a different phenotypic expression and genetic makeup,40,41so using an incorrect species of test mouse and making an extension to humans is a stretch to say the least. In studies on normal aging mice species, GH treatment extended the life span.42,43,44

Recent media reports about the federal law concerning hGH have created unnecessary confusion in the media,45and some reporters46have confused non-medical over-the-counter homeopathic sprays and nutritional products with pharmaceutical-grade, FDA-approved injection medications for AGHD patients. One university has initiated a misinformation press campaign.47 Misleading journalism incorrectly intermingles 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, have erroneously suggested that the replacement of hGH in aging adults is illegal, and has led to sensationalized headlines.45,46 Patients are not given HGH for a diagnosis or treatment of "anti-aging," but for on-label use for AGHD syndrome, a diagnosed disease.

The federal law in question is 21 U.S.C. § 333(e), a provision of the Food, Drug, and Cosmetic Act (FDCA). It says, 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." 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. Although never even mentioned in the JAMA piece, the 1988 law was written and passed regarding anabolic steroids. The legislative history of the law's creation 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 upcoming Seoul Olympics (at which, ironically, Canadian sprinter Ben Johnson's steroid positive ignited a global firestorm).

Two years later, in 1990, heightened alarm over steroids and hGH in athletics resulted in the Anabolic Steroid Control Act of 1990, which 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.48Instead, Congress took the lesser approach of inserting hGH, to replace steroids, in the FDCA law that was written to stop trafficking to cheating athletes.   The focus of lawmakers and Congress has always been to address non-medical use again, improper use by competitive elite athletes, sports people and teenagers. One of the authors of the recent 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".49 This is a very odd 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 5 years after the 1988 statute was enacted.

Despite their hyperbolic rhetoric, the co-authors of the commentary admit that hGH prescribing is perfectly legal in connection with (1) "treatment of a disease" or (2) an "other recognized medical condition" that has been authorized by FDA.   At no time has Congress evinced any intent to restrict ethical physicians from prescribing hGH to mature or elderly adults for medical reasons within their sound judgment.  Nothing in the statute dictates to physicians how to diagnose the indications for diseases which may be treated by hGH. Any inference that the statute was intended to prohibit physicians from prescribing hGH for hormone replacement purposes in GH-deficient adults is misplaced.

As we understand the statute, hormone replacement in mature, clinically GH-deficient adults is both treatment of a disease and a medical use authorized 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 incorrect and misleading. It is incumbent upon medical science writers to refrain from making biased or inflammatory statements, for agenda-driven science reporting is not scientific.

Two of the three authors of the JAMA commentary50are defendants in a $120 million lawsuit brought against them by the AmericanAcademyofAnti-Aging Medicine(as well as other plaintiff parties) for defamation, slander, conspiracy, and other claims. The defendants' attempt to have the claims dismissed in court was recently denied by the court.

Most interesting of all is that the third article by the same Forbes journalist yet again promoting the work of the lead author of the commentary in JAMA, now has turned his attention to promoting Elixir Pharmaceuticals in a Forbes cover story entitled, "Want to Live Forever?" barely a week after penning in the same publication, "Jail Time for Growth Hormone?". A curious section from this newest piece, written barely a week after the former, states: ?Elixir focuses on another molecular mechanism linked to aging, one that casts doubt on the fad of taking human growth hormone to keep you young. Mice engineered to be resistant to the effects of growth hormone or a related hormone, IGF-1, live longer than their normal counterparts, several studies have found; other mice bred to have elevated hormone levels die young. Elixir hopes to design drugs that block the effects of the natural hormone ghrelin, which prompts the release of growth hormone and stimulates appetite. The company aims to test this approach for diabetes and possibly obesity; it hopes to begin human trials in two years.51. Most profound here, is this JAMA author failed to disclose that he is in fact one of the founders of Elixir Pharmaceuticals.

Even further, a listed source for the Forbes article, is not surprisingly, the third author of the JAMA commentary.
HGH therapy has been in use for over 40 years on adults and children,52with one of the best safety records in modern pharmacia and whose dose in adults is typically only 1/3 of the pediatric dose and under the strict supervision of an endocrinologist or anti-aging specialist. Not a single death or permanent life threatening morbidity has been reported in its use of AGHD by these experts in otherwise healthy but AGHD patients. As Savine points out in the same issue of JAMA in which the subject Commentary appeared," Life without GH is poor in quantity and quality."15

References
1Langreth R. Sweet syringe of youth. Forbes.com. Available at http://www.forbes.com/global/2000/1211/0325134a.html.December 11, 2000. Accessibility verifiedSeptember 21, 2005.
2Dietary Supplement Health and Education Act of l994, Pub L No. 103-417, 103rd Congress (USC, Title 21 [Food and Drugs], Chapter 9 [Federal Food, Drug and Cosmetic Act])
3Gotherstrom G., et.al. ?A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices? Journal of Clinical Endocrinology and Metabolism, 86 (10): 4657-65, Oct. 2001.
4Gibney J, et. al., ?The Effects of 10 Years of Recombinant Human Growth Hormone, (GH) in Adult GH-Deficient Patients?, The Journal of Clinical Endocrinology and Metabolism, Volume 84, Number 8, August 1999.
5CappolaARet al.Association of IGF-I levels with muscle strength and mobility in older women. J Clin Endocrinol Metab 2001 Sep;86(9):4139-46.
6Aleman A. et al. Insulin-Like Growth Factor-I and Cognitive Function in Healthy Older Men J Clin Endocrinol Metab 84:471475, 1999.
7Sugimoto T et al. Effect of recombinant human growth hormone in elderly osteoporotic women. Clin Endocrinol (Oxf) 1999 Dec;51(6):715-724.
8NapoliR et al. J Am Coll Cardiol 2002 Jan 2;39(1):90-5.
9Johannsson G et al. GH treatment of abdominally obese men reduces abdominal fat mass, improves glusoce and lipoprotein metabolism and reduces diastolic BP. J Clin Endocinol Metab 1997;82:727-734.
10Albert SG et al. Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. Clin Endocrinol Metab. 2004 Feb;89(2):695-701.
11Nam SY et al. Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients.
12Blackman MR, Sorkin JD, Munzer T, et al. Growth hormone and sex steroid administration in healthy aged men and women, a randomized trial. JAMA, 2003. 288:2282-2292.
13Braverman, ER. Use of Growth Hormone in Elderly Individuals. JAMA, July 23/30, 2003, Vol 290:4.
14Huang X, Blackman MR, Herreman K, Pabst KM, Harman SM, Caballero B. Effect of growth hormone and/or sex administration on whoe body protein turnover in healthy aged women and men. Metabolism 2005 Sep; 54(9): 1162-7.
15Savine R. et al. Provision or distribution of growth hormone for ?antiaging?: clinical and legal issues. JAMA. 2005 Oct 26;294(16):2086-90.
16Wuster C, Melchinger U, Eversmann T, Hensen J, Kann P, von zur Muhlen A, Ranke MB, Schmeil H, Steinkamp H, Tuschy U. Reduced incidence of side-effects of growth hormone substitution in 404 patients with hypophyseal insufficiency. Results of a multicenter indications Study. Med Klin 1998 Oct 15;93(10):585-91.
17Welle S, Thornton C, Statt M, McHenry B. Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old. J Clin Endocrinol Metab 1996 Sep;81(9):3239-43.
18Pape GS, Friedman M, Underwood LE, Clemmons DR. The effect of growth hormone on weight gain and pulmonary function in patients with chronic obstructive lung disease. Chest. 1991 Jun;99(6):1495-500.
19Snel YE, Doerga ME, Brummer RJ, Zelissen PM, Zonderland ML, Koppeschaar HP. Resting metabolic rate, body composition and related hormonal parameters in growth hormone-deficient adults before and after growth hormone replacement therapy. Eur J Endocrinol. 1995 Oct;133(4):445-50.
20Svensson J, et al. J Clin Endocrinol Metab. 2004;89(7):3306-12.
21Eiser C, et al. Growth Hormone Treatment and Quality of Life among Survivors of Childhood Cancer. Horm Res. 2005; 633(6):300-4.
22Zumkeller W, et al. _Expression and synthesis of insulin-like growth factor-binding proteins in human glioma cell lines. Int J Oncol. 1998 Jan;12(1)129-35.
23Gielen SC, et al. Steroid-modulated proliferation of human endometrial carcinoma cell lines: any role for insulin-like growth factor signaling? J Soc Gynecol Investig. 2005 Jan;12(1):58-64.
24Bach LA, Headey SJ, Norton RS. IGF-binding proteins the pieces are falling into place. Trends Endocrinol Metab. 2005 July;16(5):228-34.
25Swerdlow AJ, et al. J Clin Endocrinol Metab 2000;85(12):4444-9.
26Tacke J, et al. JPEN J Parenter Enteral Nutr 2000;24(3):140-4.
27Critical Evaluation of the Safety of Recombinant GH Administration: Statement from the Growth Hormone Research Society, J Clin Endo Metab, May 2001.
28Lee, JM and Menon RK. Growth Hormone for short children without a hormone deficiency: Issues and practices. Contemporary Pediatrics, 2005 Oct, Vol 22, (10):46-50.
29Brooke AM, Monson JP. Adult growth hormone deficiency. Clin Med 2003:3:15-19.
30Braverman ER and Blum K. Adult Growth Hormone Deficiency: A Higher Compliance Delivery System. AmericanAcademyofAnti-AgingMedicine, 10thInternational Conference, December 2002.
31Bach LA.IGFBP-6 five year on; not so "forgotten"? Growth Horm IGF Res. 2005 Jun;15(3):185-92.
32Koike H, Ito K, Takezawa Y, Oyama T, Yamanaka H, Suzuki K. Insulin-like growth factor binding protein-6 inhibits prostate cancer cell proliferation: implication for anticancer effect of diethylstilbestrol in hormone refractory prostate cancer. Br. J Cancer, 2005 Apt 25;92(8):1538-44.
33Denys H, Jadidizadeh A, Amininik S, Van Dam K, Aerts S, Alman BA, Cassiman JJ, Tejpar S. Identification of IGHBP-6 as a significantly down regulated gene by beta-catenin in desmoid tumors. Oncogene. 2004 Jan 22;23(3):654-64.
34Cummings DE, Merriam GR. Growth hormone therapy in adults. Annu Rev Med. 2003;54:513-33. Epub 2001 Dec 3.
35Pandian R and Nakamoto JM. Rational use of the laboratory for childhood and adult growth hormone deficiency. Quest Diagnostics Nichols Institute.Clin Lab Med. 2004 Mar;24(1):141-174.
36Brooke AM, Monson JP. Adult growth hormone deficiency. Clin Med 2003:3:15-19.
37Braverman ER, Blum K. Adult growth hormone deficiency: A higher compliance delivery system; AmericanAcademyofAnti-Aging Medicine, 10thInternational Conference, December 2002.
38Braverman ER, Blum K. P300 Latency (An Established Marker of Brain Processing Speed) Correlates with Sex Hormones and Insulin Growth Factors (IGF-1 and 3), Poster Presentation atENDO2005, The Endocrine Society's 87thAnnual Meeting, June 4-7 in San Diego, California.
39Braverman E, Blum, K. P300 (Latency) Event-Related Potential: An Accurate Predictor of Memory Impairment : Hormonal Correlates. Alzheimer's & Dementia, Vol 1, issue 1, Suppl 1, July 2005.
40Abs R, Mattsson AF, Bengtsson B, Feldt-Rasmussen U, Goth MI et al. Isolated growth hormone (GH) deficiency in adult patients: baseline clinical characteristics and responses to GH replacement in comparison with hypopituitary patients. A sub-analysis of the KIMS database. Growth Hormone & IGF Research 15 (2005) 349-359.
41Murali SG, Nelson DW, Draxler AK, Liu X, Ney DM. Insulin-like growth factor-I (igf-I) attenuates jejunal atrophy in association with increased _expression of igf-I binding protein-5 in parenterally fed mice. J Nutr. 2005 Nov;135(11):2553-9.
42Risewijk AM, Xu YQ,SchepensMT, Marimam EM, Polichronakos C, Ropers HH, Kalscheuer VM. Absence of an obvious molecular imprinting mechanism in a human fetus with monoallelic IGF2R expression. Biochem Biophys Res Commun. 1998 Apr7;245(1)272.
43Khansari DN, Gustad T. Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice. Mech Ageing Dev. 1991 Jan;57(1):87-100.
44Sonntag WE, Carter CS, Ikeno Y, Ekenstedt K, Carlson CS, Loeser RF. Endocrinology: 2005; 146(7):2920-32.
45Langreth R. Jail Time for Growth Hormone? Forbes.com.Oct. 25, 2005.
46Forman J. Antiaging drug falls short of hype, The Boston Globe.Oct. 31, 2005.
47Growth Hormone Illegal or Off-Label Anti-Aging. University of Illinois-Chicago,Oct. 20, 2005.
48Statement of Louis Underwood, M.D., "Abuse of Steroids in Amateur and Professional Athletics," Hearing Before the Subcommittee on Crime/ House Committee on the Judiciary,March 22, 1990).
49Mitchell, S.; HGH illegal as anti-aging treatment: United Press International (UPI),Oct. 25, 2005.
50Perls et al. Provision or distribution of growth hormone for "antiaging": clinical and legal issues. JAMA. 2005 Oct 26;294(16):2086-90.
51Langreth R. Want to Live Forever. Forbes.com.Nov. 14, 2005.
52Abramow M., Corvilain J.: Metabolic effects of human growth hormone in adults and children. J Ann Endocrinol (Paris) March-April 1963, 145-56.