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Growth Hormone Use and Abuse

Over the last decade, GH has become one of the most commonly abused drugs in sports. It is being sold widely by “fitness trainers” to their clients in gyms throughout the country.

Its popularity lies in the belief that it not only possesses marked ergogenic properties, but also that its administration is currently undetectable. Current scientific evidence of its performance enhancing effect is limited. However, these limitations could be due to the study designs employed. Athletes are almost unanimous in the opinion that the illicit taking of GH is worthwhile. It is therefore likely that the scale of this abuse will increase. Of course, federal law prohibits dispensing or using any drug without a prescription, so it is illegal for anyone to receive or distribute drugs “on the street.” To do so is to face the risk of severe criminal penalties, including fines and imprisonment.

Although abuse has been reported in competitive athletes, by far the largest group that abuse GH are competitive and recreational body builders. In both groups, GH is self-administered without any medical supervision. The enormous doses injected, and the often simultaneous abuse of other substances such as the black market use of anabolic steroids lead to frequent side-effects which may be severe, if not fatal. Finally, there is a growing segment in the healthy aging “baby boomer” population that believe GH use is not only safe, but also that it is the “miracle drug that stops aging, and everyone who can afford it should be using it.”

In order to understand and responsibly administer GH replacement therapy to adults, it is necessary to first consider the differential diagnosis of adult onset GH deficiency. In addition, the study of the side-effects of recombinant human GH (rhGH) administration to GH-deficient adult patients will elucidate a scientific basis for the establishment of a standard of care protocol in the treatment of idiopathic adult-onset of GH deficiency disorder (Somatopause).

Safety Aspects of Growth Hormone Replacement in Adults

  1. A GH pulse is released roughly every second hour with a mean daily secretion of 0.5mg. GH secretion is amplified during fasting and stress, whereas meals suppress GH release.
  2. Blood sugar rises drastically following a single supraphysiologic 10 mg dose of human growth hormone (GH) to totally GH deficient adults. And, high dose of GH administration in normal adults markedly reduced forearm muscle uptake of glucose, which reduces energy production in the muscle cell.
  3. The metabolic effect of a physiologic dose of GH in the postabsorptive (digestive) state is stimulation of fatty deposit breakdown following a lag time of 2-3 hours as the most consistent effect. Plasma glucose, on the other hand exhibited only minor fluctuations, and serum insulin and C-peptide levels remained completely stable. However, there are subtle reductions in muscle glucose uptake and oxidation. By contrast, the effect of high doses of GH causes liver and muscle resistance to insulin, increased lipid oxidation to fatty acids, and reduced muscle glycogen synthesis (hastening muscle fatigability). The fatty acid build-up ultimately leads to beta cell “exhaustion” and overt to diabetes mellitus.
  4. GH deficient adults have a higher prevalence of impaired glucose tolerance as compared to healthy, age and sex-matched controls. Determinants of abnormal glucose tolerance include old age, female sex, and obesity. Paradoxically, fatty plasma levels of glucose and insulin were normal.
  5. A predominant site of insulin resistance appears to be the skeletal muscle synthase activity. The mechanism for this is unknown, but it may be due to increased free fatty acid (FFA) flux from visceral fat since visceral (abdominal) adiposity is a hallmark of adult GH deficiency. In this regard, it is noteworthy that a normal body mass index does not exclude visceral obesity.
  6. GH replacement in GH deficient adults causes fasting plasma levels of glucose and insulin to increase after 6 weeks, but returns to baseline somewhere between 3 and 18 months. GH replacement in GH deficient adults (GHDA) may cause insulin resistance and glucose intolerance, and the risk is determined by the following factors: GH dosage, body composition, cause of GH deficiency, chronological age, and duration of therapy.
  7. Fluid retention and arthralgia (joint pain) as side-effects of GH administration were first reported in 1959. These symptoms were associated with retention of sodium and increased extracellular volume. Fluid retention is also seen with IGF-I administration, and it is thought that secondary insulin resistance may be contributing to the fluid retaining effects.
  8. GH interacts with other hormones. It increases the extrathyroid conversion of T4to T3, which may unmask incipient hypothyroidism. The effect on the gonadal axis is complex and not fully clarified. It has been shown to stimulate steroidogenesis, fertilization, enhancement of peripheral (muscle) androgen actions, increase estradiol concentrations, and reduce circulatory levels of prostatic specific antigen (PSA).
  9. GH impact on glucocorticoids is very complex. Unchanged, increased, and reduced levels of basal and ACTH-stimulated cortisol levels have been reported. GH administration in hypo- pituitary GHDA adults may reduce the bioavailability of administered glucocortisol to cortisone, and one study suggests that GH reduces the level of cortisol binding globulins.
  10. Short-term treatment with GH has overall beneficial effects on cardiovascular and cerebrovascular death rates in GHDA, but information about long-term effects is lacking. Of concern in this context are the long-term effects of heart structure and function, and on lipoprotein (a) {Lp (a)}. Lipoprotein (a) is a risk factor for ischemic heart disease, and demonstrates in some studies a marked increase in response to GH administration.
  11. Short-term placebo-controlled treatment trials with GH in GHDA have demonstrate an anabolic effect on cardiac structure and increased systolic function (blood being pumped out of the heart during the contractile phase). These effects may explain the improved exercise capacity and cardiac work obtained in response to short-term GH treatment as compared with placebo controls.

Monitoring the long-term effects of GH are of major importance, mainly because of the well-known cardiovascular consequences of acromegaly. Short-term uncomplicated acromegaly results in a high cardiac output state with a reduction in peripheral resistance and increase left ventricular mass. Acromegalic patients having diabetes mellitus and hypertension also have the highest risk of developing left ventricular hypertrophy, systolic, and diastolic dysfunction.

  1. The most common reasons for growth hormone insufficiency in adults are tumors occurring in the pituitary gland or in the hypothalamic area of the brain. Chemical treatment, radiation, or surgical removal of these tumors usually results in hypopituitarism. When GH replacement was introduced to the hormone replacement protocol for treatment of hypopituitarism, one concern was the increased risk of recurrence and regrowth of these tumors. In addition, GH and IGF-I receptors are present on many cancer cells and the risk that GH replacement would increase the incidence of other tumors should be acknowledged.
  2. The few data of GH treatment on tumor recurrence and growth obtained from the pediatric literature suggest the risk was not increased by GH treatment. Published data from KIMS, the Pharmacia-UpJohn Corporation International Metabolic DATABASE, treated 1034 hypopituitary adults compared with 43 clinical trials initiated by Pharmacia Corp., involving 1145 hypopituitary patients showed no statistically significant differences between GH treated patients and controls for tumor recurrence. However, these data are considered too few to rule out concern.
  3. The reports on the occurrence of other neoplasia (cancers) during GH replacement in adults is also lacking. The risk may, however, be discussed in the context of risk of cancer in patients with acromegaly and recent data showing an association between high serum levels of IGF-I and risk of cancer. Patients with acromegaly and thus long-standing high levels of serum GH and IGF-I in retrospective trials (looking back at events that have occurred) have increased frequency of malignant disease. The most frequently found are mammary and colorectal cancers. The overall observed: expected ratio for cancer in these studies is between 1.27 and 2.5. In prospective trials (looking forward to monitor events as they occur), the rate of tubular adenomas and hyperplastic colon polyps is increased with some studies also showing more than the expected numbers of colon cancer.
  4. A meta-analysis (comparison of results from a number of separate studies), including the Physician’s Health Study, of hormonal predictors of prostate cancer found that men with either testosterone or IGF-I levels in the upper quartile of the population had an approximately two-fold higher risk of developing prostate cancer. The analysis included 28 studies of the role of sex steroids, and three studies on the role of serum IGF-I in prospective, nested case-control studies. In the Nurse’s Health Study, there was a 4.5 fold relative risk of breast cancer in the highest quartile of serum IGF-I as compared with the lowest quartile.

Similar results were also found for colorectal cancer in men in the Physician’s Health Study. That study together with the above mentioned studies of prostate and breast cancer demonstrated an inverse relationship between risk of cancer and serum IGFBP-3 concentration.

  1. The Nurse’s Health Study also demonstrated that higher plasma levels of sex steroids and prolactin in postmenopausal women are positively correlated with increased risk of breast cancer. This raises the question of the primary importance of serum IGF-I as a causative agent. Activation of the prolactin receptor in mice has been shown to be required before high levels of GH or IGF-I could be associated with the development of mammary cancer. Moreover, with increasing age the association between the GH status and serum IGF-I levels is reduced indicating that other factors including environmental or nutritional factors may be of more importance with increasing age.

This was supported by a study in a random population of 197 men and 195 women aged 25-64 years which found that serum IGF-I was, positively and independently from age, associated with plasma fibrinogen and smoking habits in men and negatively with coffee consumption in women. It should also be kept in mind that tumor cells can remain robust even though they are in a GH/IGF-I deficient setting.

We should also consider the possibility of an association between hypothalamic-pituitary tumors and other malignancy when considering the risk of GH replacement. Some studies indicate that other forms of cancer may be associated with pituitary tumors and/or their treatment.

Establishing a Standard of Care Protocol

The author recommends a standard of care protocol be established for evaluation of suspected cases of GH deficiency. This would include a preliminary work-up of a complete colonoscopy and a comprehensive cardiovascular evaluation comprising of an analysis for risk factors (genetics, lifestyle, cholesterol subtypes and particle distribution, Lp(a), fibrinogen, C-reactive protein, homocysteine, fasting insulin) and the presence of existing atherosclerotic plaque utilizing the electron beam CAT scan (EBCT), as well as all appropriate endocrine studies.

A detailed evaluation by a neuroendocrinologist of other pituitary hormones is, of course, also required in adult patients with suspected GH deficiency. Radiologic investigation of the pituitary gland should be performed using either CT or MRI, and assessment of the visual fields is obligatory, as in all patients with suspected pituitary disorders. It is recommended that all adult patients receiving GH therapy be closely supervised by a neuroendocrinologist on an ongoing basis.

Source: Theantiagingdoctor.com
“Growth Hormone Use and Abuse”

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