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With regard for the potential for an increased cancer risk with HGH treatment, peer-reviewed literature suggests the opposite. HGH treatment may upregulate 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.36–40,42 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.38–40 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, "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 al. completed a study that compared aging parameters of young (up to 39 years) and old (over 70 years) individuals having similar IGF-1 blood levels.24 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: "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 nonmedical 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 sugar intake, as evaluated by Gardner et al.44
In a landmark court case, 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.45 Forsythe comments: "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."46
DHEA
Dehydroepiandrosterone (DHEA) is the most abundant steroid in the human body and is involved in the manufacture of testosterone, estrogen, progesterone, and corticosterone.
There is evidence to suggest that DHEA may stimulate human growth hormone (HGH). Morales et al. published results of a double blind, placebo-controlled, crossover study involving 71 women and 13 men, aged 40 to 70 years.47 Subjects took 50 mg of DHEA for three months, followed by a placebo for three months. While subjects were receiving DHEA, their levels of DHEA and DHEA-S rose to that of young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. Furthermore 84% of women and 67% of men reported an improved sense of both physical and psychological well-being, including improved sleep quality, increased energy levels, improved ability to handle stress, and increased sense of relaxation. Five of the volunteers also noted improvement in chronic joint pain and mobility. The researchers also found that DHEA caused a significant rise in IGF-1 levels, although it did not affect the 24-hour measurement of HGH levels. They speculate that restoring the levels of DHEA may stimulate the liver to produce more IGF-1 or generate more HGH receptors. In other words, we may find that the anti-aging benefits attributed to DHEA may actually be due to the stimulation of the HGH- IGF-1 system.
When DHEA levels are in an optimal range, there can be less risk of developing atherosclerosis.22 Rabijewski found that DHEA could lower insulin levels and decrease the risk for developing type 2 diabetes.48 DHEA also decreases the risk of cancer because it enhances the immune system response. DHEA is also thought to be neuroprotective.
Professor Etienne-Emile Baulieu, world-known researcher and endocrinologist at INSERM in Paris, former president of the French Academy of Sciences, honorary member of College of France, known for his work on contraception and on steroid hormones, was the first to synthesize DHEA in the 1960s. Baulieu conducted numerous conclusive researches on the efficiency and benefits of DHEA. His findings underline the systematic positive results of administrating DHEA in his experimental and clinical studies, especially in men. His findings demonstrate that 50 mg of DHEA in 280 participants during a year significantly improved their bone mass, skin thickness, and pigmentation, as well as the libido in both men and women; general physical and mental well-being were improved too.49,50 In an interview for a study on anti-aging medicine, Baulieu declares: "One of the most important effects of DHEA has not yet received enough attention: it acts on the receptors of neurotransmitters. There is very encouraging research on the well being and improvement of memory in old age."51
Testosterone
Testosterone is the main hormone produced in the testicles and secreted by the testes. Testosterone deficiency has pleiotropic deleterious effects. There is increased cardiovascular system dysfunction, which can lead to the increased incidence of acute myocardial infarctions and strokes. Citing separately published data finding that "serum testosterone levels were proved to be an independent negative predictor for developing arterial stiffness, assessed from the peak systolic and end diastolic diameters of the common carotid artery and simultaneous brachial artery blood pressure," Kelly and Jones submit: "Testosterone has demonstrated anti-inflammatory effects clinically and [testosterone replacement therapy] can improve atherosclerosis assessed non-invasively in hypogonadal men and in animal studies."62
Testosterone optimization is anti-inflammatory.22 Testosterone prevents cytokine production and initiates the acute phase response, which elevates C-reactive protein, serum amyloid A, and fibrinogen. Testosterone also prevents the formation of the adhesion molecules vascular cell adhesive molecule (VCAM) and intercellular adhesive molecule (CD 54/ICAM), which are necessary components of the process of atherosclerosis. Thus, testosterone replacement is a very powerful anti-inflammatory treatment that can help to prevent atherosclerosis. Testosterone has also been shown to be of benefit in the treatment of chronic heart failure. Pugh et al. found that testosterone increases cardiac output, decreases left ventricular load, and has no adverse cardiovascular effects.53 Malkin et al. show that testosterone replacement moderates inflammatory cytokines and improves heart failure outcomes.54 Turhan et al. found that men with low free testosterone levels have greater than 3 times the risk for the development of coronary artery disease.55
There is a common misconception that testosterone has adverse cardiovascular effects.22 However, the opposite has been shown with current research. The lower the free testosterone level, the more likely that coronary artery disease will be present. Testosterone replacement therapy (TRT) improves ST depression and dilates coronary arteries. TRT also may improve lipids, and low testosterone is associated with dyslipidemia. English et al. found that low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina. Rosano et al. found that "Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease."56 The same researchers also concluded that intracoronary testosterone has direct dilating effects on the coronary arteries. Finally, Hak et al. found that low levels of endogenous androgens increase the risk of atherosclerosis in elderly men.57
Testosterone can be a very powerful tool for the control of insulin resistance.22 Replacement doses decrease insulin resistance. Low levels of testosterone play a role in the development of type 2 diabetes. Low testosterone is associated with metabolic syndrome, hypertension, type II diabetes, fibromyalgia, and coronary artery disease. Boyanov et al. studied the effect of testosterone supplementation in men with type 2 diabetes, visceral obesity, and partial androgen deficiency.58 Subjects received testosterone undecanoate, and the results reflect that supplementary testosterone reduced hemoglobin A1C levels by 17.3%, led to a decrease in visceral obesity, and improved symptoms of androgen deficiency, including erectile dysfunction. Observing, "There is strong evidence that a low testosterone level and clinical hypogonadism have a high prevalence n men with metabolic syndrome and/or type 2 diabetes," Muraleedharan and Jones conclude: "Testosterone deficiency is a risk factor in itself for the subsequent development of the metabolic syndrome and type 2 diabetes."59
Testosterone is the major predictor of skeletal mass, and it is synergistic with growth hormone (GH) and insulin-like growth factor-1 (IGF-1).22 Bhasin et al. show that testosterone can improve strength even without exercise, but there is a marked improvement if testosterone is taken in combination with exercise.60 Declining testosterone levels are associated with accelerated osteoporosis, decreased muscle mass, and anemia; that is, frailty.
Numerous studies have documented testosterone's positive effects on body composition. Mudali and Dobs write: "Studies in hypogonadal men have shown that testosterone replacement is effective in increasing muscle mass and strength and decreasing fat mass. … Current evidence suggests that testosterone replacement may be effective in reversing age-dependent body composition changes and associated morbidity."61 LeBlanc et al. analyzed data collected on 1183 men, ages 65 years and older, following the subjects for 4.5 years.62 Body composition was measured using dual energy X-ray absorptiometry (DEXA) scans, and physical performance was measured through a series of exercises that assessed grip strength, lower extremity power, walking speed, and ability to rise from a chair without the use of arms. Results showed that higher levels of testosterone were associated with reduced loss of lean muscle mass in older men, especially in those who were losing weight. In these men, higher testosterone levels were also associated with less loss of lower body strength. The study authors concluded: "Higher endogenous testosterone is associated with reduced loss of lean mass and lower extremity function in older men losing weight. Endogenous testosterone may contribute to healthy aging." Kovacheva et al. report that testosterone supplementation reverses sarcopenia in aging via regulation of myostatin and "multiple signal transduction pathways in sarcopenia," concluding; 'Testosterone reverses sarcopenia through stimulation of cellular metabolism and survival pathway together with inhibition of death pathway."63
Testosterone levels correlate with cognitive function, and TRT can improve cognitive function.22 Moffat et al. found that serum free testosterone concentration can be used to predict memory performance and cognitive status in elderly men.64 Gouras et al. showed that testosterone replacement therapy prevents the production of amyloid-beta precursor protein in men, which suggests that testosterone replacement may play a role in the prevention of Alzheimer's disease.65 A pilot study by Tan on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease revealed that mental status of those given testosterone replacement therapy improved over one year, whereas the mental status declined in those given a placebo.66 Janowsky et al. found that increasing testosterone to 150% of baseline levels in older men resulted in a significant enhancement of spatial cognition.67 A review of testosterone and cognition in elderly men by Holland et al. concluded: "Results from cell culture and animal studies provide convincing evidence that testosterone could have protective effects on brain function. Testosterone levels are lower in Alzheimer's disease cases compared to controls, and some studies have suggested that low free testosterone (FT) may precede Alzheimer's disease onset. ... Positive associations have been found between testosterone levels and global cognition, memory, executive functions, and spatial performance in observational studies."68
Studies have shown that men who have their testosterone levels restored with TRT are less likely to suffer from depression, less moody, and more sociable and have more energy. O'Connor et al. investigated the effects of TRT on self- and partner-reported aggression and mood.69 Eight hypogonadal men received 200 mg intramuscular testosterone biweekly for 8 weeks. Results showed that TRT led to significant reductions in negative mood, tension, anger, and fatigue. Aydogan et al. assessed the relationship with testosterone levels and psychological symptoms in young male patients with congenital hypogonadotropic hypogonadism (CHH).70 39 young male patients with CHH and 40 age-matched healthy males were enrolled in the study. Results showed that hypogonadal participants had more severe symptoms of sexual dysfunction, anxiety, and depression and worse quality of life. However, 6 months of TRT led to improvements in anxiety and depression scores and the life qualities of participants. TRT also improves sexual function. Khera et al. investigated if 12 months of treatment with a testosterone gel improved sexual function in hypogonadal men, as measured by the Brief Male Sexual Function Inventory (BMSFI).71 Results showed that the mean total BMSFI score significantly increased from baseline at 12 months (27.4 ± 10.3 to 33.8 ± 9.8, p < 0.001) and at each visit in all domains (sex drive/libido, erectile function, ejaculatory function, level of bother). Regression analysis indicated that increased total BMSFI score was significantly associated with increased total testosterone levels at 6 months. The authors concluded: "In hypogonadal patients, 12-month administration of topical testosterone gel resulted in increased total testosterone and free testosterone levels and significantly improved sexual function."
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