# Growth Hormone - the real "fountain of youth!"



## hackskii (Jul 27, 2003)

Growth Hormone - the real "fountain of youth!"

by James South MA

On July 5th 1990, America's most prestigious medical journal, the New England Journal of Medicine, published a human clinical study that changed the world of anti-aging medicine forever.

Daniel Rudman, MD and colleagues reported the results of their 6-month trial of synthetic human growth hormone (hGH) with 12 elderly men, aged 61 to 81. Astoundingly, without any change in diet, exercise, lifestyle, smoking etc., the 12 men gained muscle, lost fat, increased their bone density, thickened their skin and expanded their livers and spleens almost 20%.

In effect, hGH reversed the biological age of the subjects by 10 to 20 years!

hGH, the history

Prior to Rudman's landmark study, hGH use had been restricted to two classes of people: young children, whose growth was severely stunted due to serious hGH deficiency and adults whose pituitary glands had been damaged or destroyed by injury, illness or radiation.

Prior to 1985, hGH was in extremely short supply. It was painstakingly extracted from the pituitary glands of human cadavers.

Human use of hGH began in 1958 when endocrinologist Maurice Raben injected hGH into a dwarf child. The child began to grow normally and over the next 30 years thousands of children were injected with cadaver derived hGH.

By 1985 the company that pioneered recombinant DNA technology, Genentech, had produced the first synthetic hGH, opening the way to mass production of hGH.

hGH is an extremely large and complex hormone, consisting of 191 specific amino acids linked in a 3 dimensional structure. Because it is a complex protein, hGH cannot survive digestion and must be taken by injection.

Genentech's product, Protropin, differed from natural hGH by one amino acid, but this did not affect its performance in the human body. The following year, the Drug Company Eli Lilly succeeded in making a 191 amino acid hGH that was 100% physically, chemically and biologically identical to hGH produced by the human pituitary gland.

Lilly's Humatrope was also approved by the USA FDA for both research and medical use and became what many clinicians now consider the "gold standard" of recombinant DNA produced hGH. Finally in 1996, thanks to the pioneering medical and legal work of Dr. Edmund Chein, the FDA lifted its ban on the use of hGH for adult patients.

hGH clinical studies

From 1994 through 1996, over 800 people were treated with hGH at Dr. Chein's clinic. In 1995, Chein began his collaboration with Dr. L. Cass Terry. Terry used his skills as an academic researcher to help Chein turn the mass of clinical data gathered from his patients, into a meaningful statistical profile of results. These results would demonstrate to both scientists and the public, the safety and efficacy of hGH in improving a broad array of human health parameters in adults.

Chein and Terry's data were published for the first time in Dr. Ronald Klatz's 1997 book Grow young with hGH.

hGH is secreted by the pituitary gland, a tiny gland at the base of the brain. It is normally secreted in pulsatile bursts, with the largest daily amount being secreted in the first few hours of deep, slow wave sleep.

For reasons of convenience, Dr. Rudman in his 1990 study had given his 12 elderly men only 3 injections of hGH per week, at a high dose of 16 IU.

In a study published in 1996, Dr. Maxine Papadakis of UCSF reported mixed results with the identical high dose, low frequency protocol of hGH injections. Although both Rudman and Papadakis found significant multiple benefits, especially on the body composition of the subjects, they also reported some unpleasant side effects. These included carpal tunnel syndrome (wrist pain), gynocomastia (enlarged breasts), pains in both large and small joints and edema (excess fluid) in the legs.

Papadakis' team also noted, however, that the side effects disappeared or decreased markedly within 2 weeks after the hGH dose was lowered by 25 to 50%.

Chein and Terry chose to adopt an injection regimen, which more closely approximated the natural rhythms of normal hGH secretion. Their clinic patients were taught to self administer hGH injections subcutaneously (just below the skin), just before bedtime and upon arising 6 days per week. A weekly day of rest from injections was taken to prevent the patient's pituitary glands from getting "lazy" and ceasing whatever hGH secretion their gland was still releasing.

A dose of 0.3 to 0.7 IU of hGH was given twice daily, for a weekly total of about 4 to 8 IU hGH. Thus, Chein and Terry's weekly dose was only about one quarter to one half of the dose Rudman and Papadakis gave their patients 3 times weekly.

Chein and Terry have not found any major side effects among their 800 patients. Minor joint aches and pains and slight fluid retention are the only side effects they have found, and these generally disappear in the first month or two of treatment.

Chein and Terry believe their lower dose; natural rhythm hGH protocol is responsible for the minimal incidence of severity of side effects in their patients.

Based on the results of randomly selected questionnaires from 202 patients, aged 39 to 74 (15% women), Chein and Terry reported many outstanding benefits of their low dose, high frequency hGH program.

Over 80% improved, while 72% noted significant fat loss. 60 to 70% found improvement in skin texture, thickness, elasticity and wrinkle disappearance, while 38% reported new hair growth. 55 to 71% found improved healing capacity and healing of injuries, while 73% reported increased resistance to common illness.

A high incidence of improvement in sexual functioning and menstrual/ menopausal health was noted.

Also 62 to 84% of subjects enjoyed increases in energy levels, emotional stability, positive attitude and memory.

hGH's biology

To fully understand the significance of the positive results reported by Rudman, Papadakis, Chein and Terry (as well as many others too numerous to mention in this short article), it is necessary to understand the basics of the biology of hGH.

hGH is one of many hormones secreted by the pituitary gland. Hormones are chemical messengers that help guide, direct and control the complex integration between (and physiologic functions of) our organs, tissues and cells.

Just as there is a hierarchy of control in an army, with generals directing colonels, who direct majors and captains, with orders eventually directing the corporals and privates to action, so the human glandular system is ordered and functions hierarchically.

The general of the hierarchy is the human brain, which affects the connecting link between the nervous system and the glandular system- the hypothalamus. The hypothalamus portion of the brain, activated by nerve signals from elsewhere in the brain, secretes releasing hormones, which in turn cause the pituitary to release its hormones.

Pituitary hormones, such as ACTH, thyrotropin and luteinizing hormone, trigger other glands to release their hormones.

ACTH triggers the adrenals to secrete cortisol, thyrotropin causes thyroid hormone release and luteinizing hormone activates the sex glands to release their hormones.

Finally, these primary action hormones affect their target tissues- e.g. the sex hormones control the reproductive organs, thyroid hormone activates brain, liver, heart and muscles, while cortisol alters immune, brain and fat tissue, etc.

Out of all the various pituitary hormones, hGH has the most universal action, ultimately affecting every cell of the body. Unfortunately, hGH shows the greatest and most precipitous drop with age.

hGH and its age related decrease

According to data from the April 1995 Journal of NIH Research, a healthy 10-year-old might secrete 2000mcg hGH per day. By age 20 hGH secretion has already dropped to 700mcg per day (a 75% drop!). 400mcg is secreted on average by 30, while from 40 to 80 hGH drops from about 325mcg to 225mcg per day.

Yet ironically, research has shown that the somatotrophs (hGH producing cells within the pituitary) of elderly people are frequently making as much hGH as young people! The problem then lies with defective hGH release and not manufacture.

Many factors (possibly including some nutrients) enhance hGH release; many all too common factors also inhibit hGH release.

Intense exercise, adrenaline mediated stress, emotional excitement, fasting and calorie restricted diets enhance growth hormone release.

While the "state of siege" stress hormone cortisol, insulin excess and insulin resistance, obesity (especially abdominal obesity) and high blood levels of free fatty acids, all inhibit hGH release and at the same time that our cells are becoming less sensitive to hGH's effects.

When the pituitary in response to hypothalamic releasing factors secretes hGH, it only remains in the bloodstream for minutes. During this brief flare of activity, hGH induces the liver to produce various growth factors, especially Insulin like Growth Factor One (IGF-1).

While hGH has some direct benefit on the health, metabolism and structure of our trillions of cells, much of hGH's benefit is mediated through IGF-1 and other growth factors hGH induces.

Between them, hGH and IGF-1 help deliver to our cells the raw materials needed for repair and renovation.

hGH the ultimate anti-oxidant?

According to Doctors Thierry Hertaghe and Vince Giampapa the latest European research indicates hGH and IGF-1 can go beyond the current antioxidant based anti-aging remedies in slowing, preventing and reversing aging at the cellular level.

Grace Wong of Genentech has shown that as we age cell proteins, as well as the DNA and RNA that provide the blueprint for making protein and other needed cell constituents, suffer ever accumulating damage.

A major cause of this age related cellular degradation is the ever-increasing incidence of free radicals released during normal cellular activity. These free radicals activate protease's, destructive enzymes that damage and degrade essential cell proteins and structures.

Antioxidants, such as vitamins C and E, SOD, etc., can reduce cellular levels of free radicals and thus reduce activation of the damaging proteases.

But hGH can actually activate a cellular defense force of protease inhibitors. Thus, even if high levels of free radicals can't be avoided, the protease inhibitors prevent the free radicals from triggering cell destructive proteases.

Thus Hertoghe and Giampapa note that hGH and IGF-1 can do what antioxidants cannot. Antioxidants can only reduce damage to already existing cell proteins and structures. hGH and IGF-1 help pull into the cell the nutrients needed to repair renovate and rebuild cellular structures. IGF-1 can even deliver nucleic acids (the building blocks of the genes) right into the protected citadel of the cell nucleus, where the DNA and genes, which direct our cellular architecture, reside.

Thus unlike antioxidants, hGH and IGF-1 don't just reduce cellular damage, they actively promote the healing and regeneration of aging cells.

As recently as the early 1980's, many medical texts focused on hGH's role primarily as the hormone necessary to achieve normal height and bone development. Yet the clinical human researches, as well as the basic research on hGH of the past 20 years, has now shown that hGH/ IGF-1 affects every aspect of human biology.

hGH enhancing the immune system

One of the many systems that weakens as we age is our immune system. Infectious ailments that might barely bother a healthy 20-year-old may be fatal to a typically immune compromised elderly person.

A key biomarker of aging is the "involution" or disappearance of the thymus gland. The thymus gland is the director and activator of the immune system. It secretes hormones such as thymosin and thymoietin, which regulate the immune system.

The thymus also transforms immature T-cells into programmed germ killing warriors. Researchers have been able to reverse the thymic atrophy of old rats through hGH, so that their thymus glands became as large and robust as the thymus glands of healthy young rats.

It is now known that the activity of all major immune cell types, such as T-cells, B-cells, natural killer (NK) cells and macrophages, can be beneficially altered by hGH/ IGF-1.

Greg Fahey of the Naval Medical Research Institute, Bethesda MD, has noted that immune restoration has multiple benefits. These include improved ability to make DNA, have normal cell division, normal insulin sensitivity, normal thyroid hormone levels and more normal brain chemistry.

hGH affecting insulin and physical make-up

hGH's ability to normalize age impaired insulin sensitivity is an exciting area of current research. Clinical studies with hGH routinely show reductions in human body fat with simultaneous increases in lean body mass (muscle and organ tissue).

For example, in 6 months of hGH treatment at Sahlgrenska Hospital in Sweden, hGH deficient adults lost 20% of their body fat. Most of this fat loss occurred in abdominal fat, reduced by 30%, compared with a 13% reduction in peripheral (e.g. arm and leg) fat.

It is increased abdominal fat that is strongly correlated with increased incidence of heart attacks, hypertension and diabetes.

In a short term 1994 study with 9 obese women, just 5 weeks of hGH treatment was sufficient to show significant fat loss and lean tissue gain. In this double blind crossover study, the women lost an average of 4.6 pounds of body fat (mostly abdominal), while their lean body mass increased 6.6 pounds.

hGH induced losses of abdominal fat take on added significance from the viewpoint of endogenous (body produced) hGH release. Obese men make 25% less growth hormone daily and have a pulsatile GH release that is only 25% as much as a normal weight men!

It is the interaction of insulin with hGH/ IGF-1 that seems to be responsible for hGH's anti-fat pro-muscle benefits.

As people age, their cells become more insulin resistant, frequently accompanied by increased blood insulin levels at the same time. Yet as we age, not all cells become equally insulin resistant. Unfortunately, it is the lean body mass cells (muscle and organ tissue) that primarily become insulin resistant. Fat cells may even increase their insulin sensitivity!

Since insulin helps fats, sugars and amino acids from the blood enter cells, this means that our cardiac, nerve and muscle cells are being starved as we age, meanwhile our fat cells are being gorged. But insulin doesn't just help food enter our fat cells, it also directs them to turn that bonanza into body fat!

When hGH levels become adequate once again, however, it seems to reverse the situation. It directs the action of insulin toward feeding our precious heart, brain, muscle and other organ cells, while minimizing insulin's direction of food into fat cells. Also, fat cells have hGH membrane receptors and when adequate hGH activates these receptors it triggers a process called "lipolysis," breaking down existing fat.

In a very real sense, hGH puts fat cells on a diet and on fat burning "exercise programs" at the cellular level!

hGH and brain protection

hGH has also been shown to benefit the brain and mind in many ways. Scientists have discovered hGH receptors in different parts of the brain, yet it seemed that the giant hGH molecule could not pass through the blood brain barrier. Research then discovered how hGH injections could influence the brain.

When hGH was injected into the leg, there was a 10-fold increase in hGH levels in the cerebrospinal fluid that bathes the brain. Researchers also discovered that hGH seems to rebalance neurotransmitter levels, increasing mood elevating levels of beta-endorphin, one of the brain's chief "feel good" biochemicals, while simultaneously lowering excessive dopamine levels.

Excessive dopamine produces feelings of agitation, irritability and quarrelsomeness- the "grumpy old men" syndrome.

Also, research with both pituitary damaged hGH deficient adults as well as age related hGH deficient adults, has consistently shown an antidepressant, mood elevating hGH effect.

Many of the pituitary damaged (or removed) adults studied in Sweden became withdrawn, depressed, socially isolated, passive and pessimistic. After hGH treatment, many of these adults once aging became sociable, friendly, outgoing, zestful people.

The patients treated by Drs. Chein and Terry also noted improved stress resilience, more positive outlook, more joy and peace in life.

Neuroscientists have also found evidence in both humans and animals that hGH may actually reverse the typical brain shrinkage that occurs with age. While some brain cells die over the course of a lifetime, it is even more the myriad of dendritic connections between neurons that disappear with age. It is this ever changing, even renewing (if we're healthy and active) neuronal web that forms the basis for all learning and memory.

hGH/ IGF-1 seems to protect brain cells from death under non-ideal conditions. hGH also stimulates various nerve growth factors in the brain, which in turn cause new dendrites to sprout.

hGH in conclusion

The 1990's have brought the human race- for the first time in history- the technology to reverse the generally inevitable and debilitating decline in hGH secretion.

hGH research over 30 years has demonstrated with a wealth of detail, (way beyond what can even be hinted at in this short article), that hGH is the hormone of human rejuvenation and regeneration.

Even the elderly can attain hGH assisted recovery of lost strength, health and vigor of body and mind.

It is just in time, for the diet and lifestyles of late 20th century Westerners are almost perfect for producing catastrophic hGH decline.

Even in late youth and middle age, our carbohydrate, fat and calorie rich diet promotes insulin excess and high blood fats, combined with abdominal obesity, which reduces hGH secretion and effect. Our "couch potato" lifestyle fails to provide the intense exercise stimulus needed to produce pituitary hGH release. Our quietly desperate, stressful lives which we can neither flee from nor fight, causes chronic cortisol excess in many, inhibiting hGH release and promoting hGH stultifying obesity. Our modern self indulgence and lack of discipline makes it hard for most people to benefit from the cheapest and most researched method of increasing both pituitary hGH secretion, as well as cellular sensitivity to hGH- systematic under-eating, also known as long term caloric food reduction.

Thus hGH injections may provide the "jump start" our lives need, both to reverse (some of) our accumulated aging, as well as increase our own hGH production and release, with consequent rejuvenation and regeneration.Those wishing more detail on hGH, as well as an excellent technical hGH bibliography, are referred to the excellent book; Grow young with hGH by Ronald Klatz and Carol Khan (San Francisco, Harpers 1997).


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## hackskii (Jul 27, 2003)

Low levels of GH and high levels of Insulin are both associated with obesity (Bray 1983).

Lactic Acid may be the trigger substrate for GHRH (Growth Hormone releasing hormone)

GH levels generally and peak GH levels particularly drop 40% from age twenty-thirty and another 40% from age thirty-forty. There is a further drop beyond this with increasing age.

All GH levels, especially exercise induced GH release, decline rapidly through the thirties (Bazzare 1975, Prinz 1976, Zadik 1985).

GH blocks Insulin activity, stopping Glucose uptake into muscle cells.

High Glycemic Carbs block GH releasers.

It is GH's similarity to Insulin that causes fat loss by blocking Insulin's conversion of Glucose to fat.

GH encourages the use of fat for energy (Murad 1980).

Both GH and Insulin are required for muscle growth.

10 Grams of oral Arginine powder 1 Hour (1.5 Hours for capsules) produces GH release sufficient for fat burning and muscle growth when coupled with peak output exercise. (Individuals over 200 lbs probably need 12 Grams of Arginine.)

While Thyroid Stimulating Hormone may release GH, Thyroid Hormone itself (Thyroxine) does not.

The Hypothalamus produces GHRH which causes the Pituitary to release STH. There may be a number of intermediary and/or supplementary hormone secretions from various glands We are unaware of any definitive research on which hormones trigger or block other hormone secretions and in what order or at what levels. Among the secretions affected, in addition to GH, are Prolactin, Luteinizing Hormone, Follicle Stimulating Hormone, Thyroid Stimulating Hormone and, as previously mentioned, Insulin.

The point is that while the muscle press applauded GH releasers and has now become almost dismissive of them and is now dealing with Insulin in somewhat the same way, the picture is far more complex then any of these journals have reported. As an example, to insure GH releaser effectiveness, a five hour time window is necessary, 3 hours before and two hours after. This window can be manipulated through the use of other substrates. Niacin, for example can be used to more rapidly reduce blood sugar levels but careful attention to dosage levels and timing are absolutely essential to the use of GH releasing nutrients. Moreover, this was made clear by Pearson and Shaw when they first introduced the idea to the bodybuilding world. (Though the Baryology (weight-control) research community had been aware of it for some time before.)

The GH release effect of Arginine is through Acetyl-Choline release. Acetyl-Choline levels must be kept high if GH release efforts are to be successful.

Low Potassium levels (as from diuretics), block GH release.

Phenylalanine and/or Tyrosine do not cause GH release but are involved in CCK production and thus appetite control.

Ornithine is twice as effective as Arginine in causing GH release.

Since Arginine causes an Insulin release, even in the absence of raised blood sugar levels, it produces a form of reactive hypoglycemia which accounts for a small portion of its GH Release action. This portion of the Arginine generated GH release is less affected by the proximity of dose administration to other protein intake.

The use of Melatonin may encourage GH release through the same mechanism as Tryptophan, the increase in serotonin levels at night.

The use of B-6 (pyridoxine) to augment exercise-induced GH release may work in individuals over age 30. If it does, it would require a 600 Mg oral dose 45 minutes before exercise. There are two problems with this approach: If it is used frequently, peripheral neuralgia may develop. Even occassional use can produce psychological depression which may last for days afterward.


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## hackskii (Jul 27, 2003)

Growth Hormone and Aging

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A fountain of youth? We've got plenty of youth. What we need is a fountain of smart.

Normal Changes in the Growth Hormone Axis with Aging

The rate of GH secretion from the anterior pituitary is highest around puberty, and declines progressively thereafter. This age-related decline in GH secretion involves a number of changes in the GH axis, including decreased serum levels of insulin-like growth factor-1 (IGF-1) and decreased secretion of growth hormone-releasing hormone from the hypothalamus. The cause of the normal age-related decrease in GH secretion is not well understood, but is thought to result, in part, from increased secretion of somatostatin, the GH-inhibiting hormone.

Normal aging is accompanied by a number of catabolic effects, including a decrease in lean mass, increase in fat mass, and decrease in bone density. Associated with these physiologic changes is a clinical picture often referred to as the somatopause: frailty, muscle atrophy, relative obesity, increased frequency of fractures and disordered sleep.

These clinical signs of aging are, without doubt, the manifestation of a very complex set of changes which involve, at least in part, the GH-axis. Naturally, this has spurred considerable interest in administering supplemental GH as a "treatment" for aging in humans, and the availability of recombinant human GH has made such studies feasible.

In contrast to the view that GH deficiency contributes to the aging phenomenon, there is information suggesting that normal or high levels of GH may accelerate aging. Mice with genetic dwarfism due to deficiency in GH, prolactin and thyroid-stimulating hormone live considerably longer than normal mice, and the increased levels of GH seen with acromegaly in humans are associated with reduced life expectancy. Both of these findings are likely due to metabolic effects of GH.

GH Replacement Therapy in GH-deficient Adults

Adult-onset GH deficiency in humans is almost always due to pituitary disease, usually from a tumor or therapeutic efforts to treat a tumor. Such patients have increased risk of death from cardiovascular disease, and, relative to age-matched controls, show increased fat mass, reduced muscle mass and strength, lower bone density, and higher serum lipid concentrations. Additionally, they suffer from reduced vigor, sexual dysfunction and emotional problems.

More than a dozen clinical trials have sought to evaluate GH replacement in patients with adult-onset deficiency. The goal has usually been to normalize serum IGF-1 concentrations by daily injections of GH. In essentially all cases, several months of GH replacement therapy led to increased lean mass and decreased adiposity (especially in visceral fat). The effects of GH treatment on bone density and hyperlipidemia has been inconsistent or minor, as have been the effects on strength and mental abilities. Common side effects observed in these trials included edema and joint/muscle pain, which appeared related to dose of GH. Since the first of these trials was conducted in 1988, long term risks are not yet known.

GH Therapy in the Elderly

Long before Ponce de Leon went in search of the legendary fountain of youth, people sought treatments to prevent or reverse the effects of aging. In 1990, considerable excitement was generated from a report by Rudman and colleagues which described wonderful effects of GH treatment in a small group of elderly men. These volunteers, who ranged in age from 61 to 81 years, showed increased lean body and bone mass, decreased fat mass and, perhaps most dramatically, restoration of skin thickness to that typical of a 50-year-old.

The study cited above and a handful of others have provided an initial understanding of the benefits, limitations and risks of sustained (6 to 12 month) GH supplementation in elderly men and women. A consistent finding in these investigations was a high incidence of adverse side effects - edema, fluid retention and carpal tunnel syndrome - which necessitated reductions in GH dose of cessation of treatment. GH treatment consistently induced an increase in serum IGF-1, a decrease in fat mass and increase in lean mass.

The effects on fat and lean masses may be viewed as positive effects, but, at the end of the day, it has to be asked whether GH treatment improved functioning in the elderly. In the studies in which function was objectively assessed, GH treatment did not improve cognitive function, and, despite the effects on lean body mass, was not any more effective than exercise alone in promoting strength. Long-term GH therapy in elderly postmenopausal women lead to significant increases in bone mineral density, but these increases were less than what is routinely achieved with estrogen replacement. While it must be acknowledged that a relatively small number of elderly patients have been treated for prolonged periods with GH, the controlled trials conducted thus far do not support is efficacy in aleviating age-related deficits in cognitive or somatic function.

Another indication of potentially serious side effects of GH therapy in adults, including the elderly, has been provided by controlled clinical trials that assessed the utility of human GH treatment in critical illness, where endogenous GH secretion is typically suppressed. GH therapy was anticipated to attenuate the catabolic effects of illness and thereby decrease duration of hospitalization. The results of several clinical trials involving hundreds of patients, demonstrated a significant increase in mortality associated with high doses of GH. Additionally, those patients treated with GH that survived had longer periods of intensive care and hospitalization than those receiving placebos.

References and Reviews

Borst SE and Lowenthal DT: Role of IGF-1 in muscular atrophy of aging. Endocrine 7:61-63, 1997.

Cummings DE and Merriam GR: Growth hormone therapy in adults. Annu Rev Med 54:513-533, 2003.

Holloway L, Butterfield G, Hintz RL, et al.: Effect of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. J Clin Endocrinol Metab 79:470-479, 1994.

Marcus R and Hoffman AR: Growth hormone as therapy for older men and women. Annu Rev Pharmacol Toxicol 38:45-61, 1998.

Papadakis MA, Grady D, Black D, et al.: Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Int Med 124:708-716, 1996.

Rudman D, Feller AG, Nagraj HS, et al.: Effects of human growth hormone in men over 60 years old. New Eng J Med 323:1-6, 1990.

Taaffe DR, Pruitt L, Reim J, et al.: Effects of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab 79:1361-1366, 1994.

Takala J, Ruokonen E, Webster NR, et al.: Increased mortality associated with growth hormone treatment in critically ill adults. New Eng J Med 341:785-792, 1999.

Vance ML and Mauras N: Drug therapy: Growth hormone therapy in adults and children. New Eng J Med 341:1206-1216, 1999.


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## hackskii (Jul 27, 2003)

Age-Related Changes in Growth Hormone Secretion: Should the Somatopause Be Treated?

from Seminars in Reproductive Medicine

David E. Cummings, M.D. and George R. Merriam, M.D., Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine and VA Puget Sound Health Care System, Seattle and Lakewood, Washington.

Abstract and Introduction

Abstract

Growth hormone (GH) secretion declines progressively with aging, and many age-related changes resemble those of the adult GH deficiency (GHD) syndrome, including a decrease in lean body mass; an increase in body fat, especially in the visceral/abdominal compartment; adverse changes in lipoproteins; and a reduction in aerobic capacity. The increase in central obesity can further inhibit GH secretion. GH replacement is effective in reversing many of these changes in adult GHD, and GH is now FDA approved for treatment of adults with documented GHD or hypopituitarism, although there is still only limited experience with its long-term benefits, side effects, and risks. This early experience with GHD has led to speculation that replacing GH or stimulating its secretion may also be beneficial in normal aging, and to widespread off-label use of GH in this context; however, there are still very few well controlled studies of the effects and side effects of GH or GH secretagogues in aging. All published studies are of 6 months or shorter treatment periods. From this limited experience there is a consensus that GH has effects on body composition, but reports disagree on effects on psychological or physical functional performance. Older adults are much more susceptible to the dose-related side effects of GH, including peripheral edema, carpal tunnel syndrome, and a variable decrease in insulin sensitivity; and it is not known whether chronic GH treatment affects the risk of malignancy or has other long-term risks. Thus while short-term results are somewhat encouraging, the evidence on risks and clinically pertinent benefits is still lacking to support the use of GH in normal aging outside of clinical studies. In evaluating patients with clinical features suggesting GHD, which can be quite nonspecific, it is important to assess the presence or absence of true GH deficiency by the context (pituitary disease or its treatment, childhood GHD) and by appropriate GH stimulation tests before considering GH replacement.

Introduction

Growth hormone (GH) is an important regulator of body composition, aerobic capacity, and metabolism throughout life, but its name has focused attention on its role in promoting linear growth in childhood and, until recently, away from its many functions in adults. Growth hormone deficiency (GHD) is compatible with life except in rare patients with persistent hypoglycemia. In the past there seemed no compelling argument to treat adults with GHD who had reached final stature with what was then a scarce pituitary extract or even to investigate its ongoing roles and effects. As early as 1962, however, Raben[1] reported improved vigor, well-being, and ambition in a 35-year-old hypopituitary patient treated with extracted pituitary GH, suggesting that it might continue to play a significant role in adults. When recombinant GH became available in potentially unlimited quantities, several groups revisited the syndrome of GHD in adults and the effects of GH replacement. There are now more than 1000 published studies of adult GHD, and the use of GH replacement in this context has been approved by the Food and Drug Administration (FDA).

Less clear are the functional consequences of the decline in GH secretion that occurs with aging or the relative benefits and risks of GH replacement in older adults who would not be considered GH deficient in the classical sense. Secretion of GH varies markedly across the life cycle, reaching a peak in adolescence and then declining with age in both men and women, in a pattern that implicates both the effects of gonadal steroid withdrawal and effects that are age related and independent of steroid hormone levels.[2,3] The levels of GH and its downstream effector insulin-like growth factor-I (IGF-I) in old age overlap those of younger adults with classical GHD, and many age-associated changes resemble those of GHD. These include an increase in body fat, especially visceral and abdominal fat, reductions in muscle and bone mass, reduced cardiac output and aerobic capacity, and changes in circulating lipid profiles that are atherogenic in other contexts.[4,5] These parallels have prompted speculation that GH might be used to reverse some age-related changes even in otherwise normal adults. Beginning with the studies of Rudman and colleagues,[6] a few studies have examined the short-term effects of stimulating or replacing GH in normal aging, although the number of published trials is still very limited. Although there has been a proliferation of clinics organized specifically to offer GH and other "antiaging" hormone replacement to normal older adults with the means to pay for it, GH is still not approved for this use in any country, and the balance of risks and benefits remains largely uncertain.

This article reviews the current state of knowledge of the age- and menopause-related decline in GH secretion, which some have called the "somatopause" -- its underlying mechanisms, interactions of sex steroids with GH secretion and GH action, the model of adult GHD as a guide to what treatment effects and side effects might be expected, and the limited available information about the effects of GH stimulation or replacement in normal aging.


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## hackskii (Jul 27, 2003)

High-carb diets may be appropriate in many situations but, since hyperglycaemia (elevated blood carbohydrate) tends to switch off human growth hormone (hGH) secretion, this strategy may not be appropriate where optimal adaptation is the priority. Fat taken before exercise has also been found to reduce human growth hormone (hGH) secretion (2).

It is hard to argue against the use of carbohydrate immediately after training in the few days leading up to a competition, when it is important to ensure that carbohydrate stores in the muscles are fully repleted. However, this is not the best strategy for maintaining the release of human growth hormone (hGH) after exercise, particularly if the carbs have a high glycaemic index, as these (sugary) foods stimulate insulin secretion which, in turn, contributes to a reduction in human growth hormone (hGH) (3).

It is also important to drink plenty of water during training, as dehydration has been shown to significantly reduce the exercise-induced human growth hormone (hGH) response (4).

As far as supplementation before exercise is concerned, it has been shown that ingestion of 1.5g of arginine will increase human growth hormone (hGH) secretion by blocking release of the hGH-inhibitor somatostatin, I also read 1.5 g of lysine as well although some studies have suggested this causes gastric disturbance(5). However, 2g of glutamine will lead to elevation of human growth hormone (hGH) 90 minutes later without side effects (6). It may also be a good idea to ingest some amino acids after exercise, as this has been shown to enhance human growth hormone (hGH) secretion too (7).

In terms of training, research has shown that to achieve an elevation of human growth hormone (hGH) above baseline you need to spend at least 10 minutes training at above lactate threshold intensity (8) This results in the biggest volume of human growth hormone (hGH) secreted in response to a single exercise bout, with levels of the hormone declining gradually over a period of an hour. It is also known that multiple daily sessions can give rise to optimal human growth hormone (hGH) secretion over a 24-hour period.

One study investigating the effects of three exercise sessions a day with either 1.5 or three-hour recovery periods between them found that the longer recoveries led to the greatest volume of 24-hour human growth hormone (hGH) secretion (9). Another showed an even larger human growth hormone (hGH) peak in response to sprints on an exercise bike (10).

In the light of the above-mentioned research and current recommendations for both diet and exercise, it might be a good idea to think about 'periodising' diet in a similar way to training. During periods of training, when we are trying to increase muscle mass, minimise body fat and maximise the adaptive response to training, it would seem logical to adopt an hGH-enhancing approach, reverting to a high-carb diet before and during competition.

Exercise and dietary strategies

In summary, then, exercise above lactate threshold induces the secretion of human growth hormone (hGH), promoting the use of fat as fuel. This, in turn, spares muscle carbohydrate, keeps body fat down and muscle mass high and enhances adaptation to specific exercise stimuli. The benefits are clear, but simply switching to high intensity work for the whole year is not the answer; rather, a periodised programme, where the number of sprints or higher intensity workouts alters according to the competitive programme, is the best way forward.

A suggested exercise and dietary strategy for optimising human growth hormone (hGH) secretion is as follows:

Exercise - three sessions per week, each involving at least 10 minutes' work above lactate threshold or a number of sprints, with a 1:3 work-rest ratio;

Before exercise - no fat for 60 minutes before, 2g glutamine 60-90 minutes before;

During exercise - plenty of plain water (ie 200 ml every 10-15 minutes if training in 18-21°C);

After exercise - avoid sugar for two hours post exercise but take 25g protein immediately afterwards in the form of either a protein shake, protein bar, lean meat or eggs (although you should limit your consumption of eggs to avoid too much cholesterol).

Richard Godfrey

References

Growth hormone and IGF Research 8(suppl B) : 127-9, 1998

Journal of Clinical Endocrinology and Metabolism, 76(6): 1418-22, 1993

Metabolism 48(9): 1152-6

European Journal of Endocrinology, 45(4): 445-50, 2001

American Journal of Physiology; Regulative and Integrative Comparative Physiology 279(4):R1455-66, 2000

American Journal of Clinical Nutrition, 61: 1058-1061, 1995

Medicine and Science in Sports and Exercise, 31(12): 1748-54, 1999

Journal of Endocrinology and Metabolism, 75: 157-162, 1992

Journal of Applied Physiology, 83(5): 1756-1761, 1997

European Journal of Applied Physiology, 72: 460-467, 1996


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## hackskii (Jul 27, 2003)

Review of the benefits and dangers of supplementing with growth hormone enhancers

GH Enhancers: Are They Worth the Risk?

by Hans R. L****n, MSc ChE

Growth hormone (GH) enhancers are getting a great deal of attention these days especially among bodybuilders. An 8-week course of GH enhancer is reputed to produce 15 or more pounds of solid muscle when combined with regular weight training(1).

Human growth hormone is necessary for growth and a deficiency produces short people. GH does not actually stimulate growth directly, but causes the release of insulin-like growth factors, particularly insulin-like growth factor 1 or IGF-1. It is IGF-1 that is responsible for growth and it stimulates the synthesis of lean muscle mass in particular. Human IGF-1 levels vary with age; they are particularly high during puberty and by the age of 60 years they are only about half the average value (200 micrograms/liter) of a younger adult(2,3).

Experiments to increase IGF-1 levels in older men through injections of recombinant (synthetic) GH produced astounding results. An 8.8% increase in lean body mass, a 14.4% decrease in fatty tissue, a 1.6% increase in vertebral bone density, and a 7.1% increase in skin thickness were reported by American medical researchers in 1990. Their trial lasted a year and although the 21 participants all remained healthy except for one who developed prostate cancer, the researchers warned that side effects such as edema, hypertension, diabetes, and enlargement of the heart could occur with prolonged use of synthetic GH. Other researchers found that GH injections in young people produced larger muscles and kidneys. More recently GH injections have become popular among athletes as a super- efficient way to increase muscle mass and strength(1,4).

Growth hormone is naturally secreted by cells in the pituitary gland and acts on the liver to produce IGF- 1. IGF-1 levels are normally quite steady, but increase during periods of excessive stress, through exercise, and by consuming a diet rich in certain amino acids especially arginine, ornithine, glycine, and lysine. These amino acids act directly on the pituitary gland to stimulate the production of GH and its downstream fellow hormone, IGF-1. So why not just eat a lot of these amino acids if you want to grow bigger muscles? Unfortunately, or perhaps fortunately as we shall see later, stomach acid is very tough on amino acids and only 10% or less of them actually survive long enough to get into the blood stream. This is where GH enhancers play a role. These products use a patented process to protect the amino acids in the stomach and as a result 90% or more of them are absorbed into the blood stream. It is claimed that the resulting flooding of the pituitary gland with the raw materials it needs to produce growth hormone can result in IGF-1 level increases of 200% or more. Surprise, surprise! The body has a built- in mechanism to prevent IGF-1 levels from going too high. Somatostatin is released by the hypothalamus and its major role is to keep IGF-1 levels under control. Another challenge for supplement purveyors? Not really since GH enhancers also contain special peptides which suppress the natural release of somatostatin(1-3).

Now, why would the body go out of its way to prevent high IGF-1 levels when they result in rippling muscles, sculpted bodies, and virtual 10 to 20 year age reversal in older men? Why indeed? The answer is simple, excessive IGF-1 levels can make you very, very sick and yes, they can actually kill you! High IGF-1 levels in children who are not yet fully grown cause gigantism and excessive levels in adults are associated with acromegaly. Acromegaly is not a fun thing with such manifestations as fatigue, co**** facial features, headaches, decreased vision, congestive heart failure, kidney stones, joint pains, and of particular interest to young men, impotence and a lack of sexual desire. It is said that acromegalics look more like each other than like their own family members. As a matter of fact, some pictures of bodybuilders on GH enhancers look suspiciously like the classic depictions of acromegalics. Acromegalics also have higher incidence of cancer especially colon cancer and pituitary tumors(2,5).

OK you may say, I can live with this as long as I have the largest muscles on the block. But can you also live with prostate, lung, and colon cancer? Researchers at the National Institutes of Health reported a connection between cancer risk and high IGF-1 levels in 1995. In 1998 researchers at the Harvard School of Public Health reported that a high IGF-1 level is the single most important risk factor for prostate cancer and that high IGF-1 levels were present many years before the cancer was actually diagnosed. Other researchers have found that high IGF-1 levels combined with high testosterone levels are a potent risk. High IGF-1 levels have also been implicated as strong risk factors in breast and colon cancers and now lung cancer is about to be officially added to this list. Recent research has shown that artificially increasing IGF-1 levels in mice accelerates the growth of cancerous tumors(5-10).

Dr. Samuel Epstein, MD, a professor at the University of Illinois School of Public Health says that "Taking supplements to increase your IGF-1 levels is reckless, extreme, and bordering on the criminal". Dr. Derek LeRoith of the National Institutes of Health agrees and says that there is now enough evidence that taking GH supplements when you are not deficient will increase the risk of cancer and acromegaly. Says Dr. LeRoith "If you ask me if I would take them, the answer is a definite no". Dr. Michael Pollak, a member of the Harvard team who reported the prostate cancer connection also condemns the use of GH enhancers by normal, healthy individuals. Dr. Pollak points out that growth hormone supplementation has a definite place in medicine in cases where people are deficient and need to increase their IGF-1 levels from sub-normal to normal. However, people who have normal levels would run a significantly increased risk of acromegaly and prostate cancer if they were to take GH enhancers on a sustained basis. Dr. Pollak is also concerned about giving IGF-1 to older people with normal levels for their age. He says the benefits are uncertain and the risks unknown.(5,11-13).

A distinguished group of researchers at the University of Bristol in the UK recently voiced their concern about the increasing use of IGF-1 and growth hormone enhancers by bodybuilders and elderly people trying to recapture their youth. Says Dr. George Davey Smith "People using growth hormone and IGF-1 enhancers are unlikely to be aware of their potentially harmful effects".(14)

REFERENCES

Ironman, November 1998, pp. 54-6, 192

Harrison's Principles of Internal Medicine, 12th edition, McGraw-Hill, NY, 1991, pp. 1660-82

Williams Textbook of Endocrinology, 8th edition, W.B. Saunders Company, 1992, pp. 175-77 and 1096-1106

Rudman, Daniel, et al. Effects of human growth hormone in men over 60 years old. New England Journal of Medicine, Vol. 323, July 5, 1990, pp. 1-6

Conversation with Dr. Derek LeRoith on October 1, 1998

LeRoith, D., et al. The role of the insulin-like growth factor-I receptor in cancer. Annals of the New York Academy of Sciences, Vol. 766, September 7, 1995, pp. 402-08

Chan, June M., et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science, Vol. 279, January 23, 1998, pp. 563-66

Mantzoros, C.S., et al. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. British Journal of Cancer, Vol. 76, No. 9, 1997, pp. 1115-18

Hankinson, Susan E., et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. The Lancet, Vol. 351, May 9, 1998, pp. 1393-96

Butler, A.A., et al. Stimulation of tumor growth by recombinant human insulin-like growth factor-I (IGF-I) is dependent on the dose and the level of IGF-I receptor expression. Cancer Research, Vol. 58, July 15, 1998, pp. 3021-27

Conversation with Dr. Samuel Epstein on September 28, 1998

Conversation with Dr. Michael Pollak on October 1, 1998

Carter, W.J. Effect of anabolic hormones and insulin-like growth factor-I on muscle mass and strength in elderly persons. Clinics in Geriatric Medicine, Vol. 11, November 1995, pp. 735-48

Smith, George Davey, et al. Cancer and insulin-like growth factor-1. British Medical Journal, Vol. 321, October 7, 2000, pp. 847-48 (editorial)


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## hackskii (Jul 27, 2003)

Now for the bad news.

What is acromegaly?

Acromegaly is a hormonal disorder that results from too much growth hormone (GH) in the body. The pituitary, a small gland in the brain, makes GH. In acromegaly, the pituitary produces excessive amounts of GH. Usually the excess GH comes from benign, or noncancerous, tumors on the pituitary. These benign tumors are called adenomas.

Acromegaly is most often diagnosed in middle-aged adults, although symptoms can appear at any age. If not treated, acromegaly can result in serious illness and premature death. Acromegaly is treatable in most patients, but because of its slow and often "sneaky" onset, it often is not diagnosed early or correctly. The most serious health consequences of acromegaly are type 2 diabetes, high blood pressure, increased risk of cardiovascular disease, and arthritis. Patients with acromegaly are also at increased risk for colon polyps, which may develop into colon cancer if not removed.

When GH-producing tumors occur in childhood, the disease that results is called gigantism rather than acromegaly. A child's height is determined by the length of the so-called long bones in the legs. In response to GH, these bones grow in length at the growth plates-areas near either end of the bone. Growth plates fuse after puberty, so the excessive GH production in adults does not result in increased height. However, prolonged exposure to excess GH before the growth plates fuse causes increased growth of the long bones and thus increased height. Pediatricians may become concerned about this possibility if a child's growth rate suddenly and markedly increases beyond what would be predicted by previous growth and how tall the child's parents are.

[Top]

What are the symptoms of acromegaly?

The name acromegaly comes from the Greek words for "extremities" and "enlargement," reflecting one of its most common symptoms-the abnormal growth of the hands and feet. Swelling of the hands and feet is often an early feature, with patients noticing a change in ring or shoe size, particularly shoe width. Gradually, bone changes alter the patient's facial features: The brow and lower jaw protrude, the nasal bone enlarges, and the teeth space out.

Overgrowth of bone and cartilage often leads to arthritis. When tissue thickens, it may trap nerves, causing carpal tunnel syndrome, which results in numbness and weakness of the hands. Body organs, including the heart, may enlarge.

Other symptoms of acromegaly include

joint aches

thick, co****, oily skin

skin tags

enlarged lips, nose, and tongue

deepening of the voice due to enlarged sinuses and vocal cords

sleep apnea-breaks in breathing during sleep due to obstruction of the airway

excessive sweating and skin odor

fatigue and weakness

headaches

impaired vision

abnormalities of the menstrual cycle and sometimes breast discharge in women

erectile dysfunction in men

decreased libido

[Top]

What causes acromegaly?

Acromegaly is caused by prolonged overproduction of GH by the pituitary gland. The pituitary produces several important hormones that control body functions such as growth and development, reproduction, and metabolism. But hormones never seem to act simply and directly. They usually "cascade" or flow in a series, affecting each other's production or release into the bloodstream.

GH is part of a cascade of hormones that, as the name implies, regulates the physical growth of the body. This cascade begins in a part of the brain called the hypothalamus. The hypothalamus makes hormones that regulate the pituitary. One of the hormones in the GH series, or "axis," is growth hormone-releasing hormone (GHRH), which stimulates the pituitary gland to produce GH.

Secretion of GH by the pituitary into the bloodstream stimulates the liver to produce another hormone called insulin-like growth factor I (IGF-I). IGF-I is what actually causes tissue growth in the body. High levels of IGF-I, in turn, signal the pituitary to reduce GH production.

The hypothalamus makes another hormone called somatostatin, which inhibits GH production and release. Normally, GHRH, somatostatin, GH, and IGF-I levels in the body are tightly regulated by each other and by sleep, exercise, stress, food intake, and blood sugar levels. If the pituitary continues to make GH independent of the normal regulatory mechanisms, the level of IGF-I continues to rise, leading to bone overgrowth and organ enlargement. High levels of IGF-I also cause changes in glucose (sugar) and lipid (fat) metabolism and can lead to diabetes, high blood pressure, and heart disease.

Pituitary Tumors

In more than 95 percent of people with acromegaly, a benign tumor of the pituitary gland, called an adenoma, produces excess GH. Pituitary tumors are labeled either micro- or macro-adenomas, depending on their size. Most GH-secreting tumors are macro-adenomas, meaning they are larger than 1 centimeter. Depending on their location, these larger tumors may compress surrounding brain structures. For example, a tumor growing upward may affect the optic chiasm-where the optic nerves cross-leading to visual problems and vision loss. If the tumor grows to the side, it may enter an area of the brain called the cavernous sinus where there are many nerves, potentially damaging them.

Compression of the surrounding normal pituitary tissue can alter production of other hormones. These hormonal shifts can lead to changes in menstruation and breast discharge in women and erectile dysfunction in men. If the tumor affects the part of the pituitary that controls the thyroid-another hormone-producing gland-then thyroid hormones may decrease. Too little thyroid hormone can cause weight gain, fatigue, and hair and skin changes. If the tumor affects the part of the pituitary that controls the adrenal gland, the hormone cortisol may decrease. Too little cortisol can cause weight loss, dizziness, fatigue, low blood pressure, and nausea.

Some GH-secreting tumors may also secrete too much of other pituitary hormones. For example, they may produce prolactin, the hormone that stimulates the mammary glands to produce milk. Rarely, adenomas may produce thyroid-stimulating hormone. Doctors should assess all pituitary hormones in people with acromegaly.

Rates of GH production and the aggressiveness of the tumor vary greatly among people with adenomas. Some adenomas grow slowly and symptoms of GH excess are often not noticed for many years. Other adenomas grow more rapidly and invade surrounding brain areas or the venous sinuses, which are located near the pituitary gland. Younger patients tend to have more aggressive tumors. Regardless of size, these tumors are always benign.

Most pituitary tumors develop spontaneously and are not genetically inherited. They are the result of a genetic alteration in a single pituitary cell, which leads to increased cell division and tumor formation. This genetic change, or mutation, is not present at birth, but happens later in life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells. It permanently switches on the signal that tells the cell to divide and secrete GH. The events within the cell that cause disordered pituitary cell growth and GH oversecretion currently are the subject of intensive research.

Nonpituitary Tumors

Rarely, acromegaly is caused not by pituitary tumors but by tumors of the pancreas, lungs, and other parts of the brain. These tumors also lead to excess GH, either because they produce GH themselves or, more frequently, because they produce GHRH, the hormone that stimulates the pituitary to make GH. When these nonpituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve.

In patients with GHRH-producing, nonpituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Physicians should carefully analyze all "pituitary tumors" removed from patients with acromegaly so they do not overlook the rare possibility that a tumor elsewhere in the body is causing the disorder.

How common is acromegaly?

Small pituitary adenomas are common, affecting about 17 percent of the population. 1 However, these tumors rarely cause symptoms or produce excess GH. Scientists estimate that three to four out of every million people develop acromegaly each year and about 60 out of every million people suffer from the disease at any time. 2 Because the clinical diagnosis of acromegaly is often missed, these numbers probably underestimate the frequency of the disease.

How is acromegaly diagnosed?

Blood tests

If acromegaly is suspected, a doctor must measure the GH level in a person's blood to determine if it is elevated. However, a single measurement of an elevated blood GH level is not enough to diagnose acromegaly: Because GH is secreted by the pituitary in impulses, or spurts, its concentration in the blood can vary widely from minute to minute. At a given moment, a person with acromegaly may have a normal GH level, whereas a GH level in a healthy person may even be five times higher.

More accurate information is obtained when GH is measured under conditions that normally suppress GH secretion. Healthcare professionals often use the oral glucose tolerance test to diagnose acromegaly because drinking 75 to 100 grams of glucose solution lowers blood GH levels to less than 1 nanogram per milliliter (ng/ml) in healthy people. In people with GH overproduction, this suppression does not occur. The oral glucose tolerance test is a highly reliable method for confirming a diagnosis of acromegaly.

Physicians also can measure IGF-I levels, which increase as GH levels go up, in people with suspected acromegaly. Because IGF-I levels are much more stable than GH levels over the course of the day, they are often a more practical and reliable screening measure. Elevated IGF-I levels almost always indicate acromegaly. However, a pregnant woman's IGF-I levels are two to three times higher than normal. In addition, physicians must be aware that IGF-I levels decline with age and may also be abnormally low in people with poorly controlled diabetes or liver or kidney disease.

Imaging

After acromegaly has been diagnosed by measuring GH or IGF-I levels, a magnetic resonance imaging (MRI) scan of the pituitary is used to locate and detect the size of the tumor causing GH verproduction. MRI is the most sensitive imaging technique, but computerized tomography (CT) scans can be used if the patient should not have MRI. For example, people who have pacemakers or other types of implants containing metal should not have an MRI scan because MRI machines contain powerful magnets.

If a head scan fails to detect a pituitary tumor, the physician should look for nonpituitary "ectopic" tumors in the chest, abdomen, or pelvis as the cause of excess GH. The presence of such tumors usually can be diagnosed by measuring GHRH in the blood and by a CT scan of possible tumor sites.

Rarely, a pituitary tumor secreting GH may be too tiny to detect even with a sensitive MRI scan.

How is acromegaly treated?

Currently, treatment options include surgical removal of the tumor, medical therapy, and radiation therapy of the pituitary.

Goals of treatment are to

reduce excess hormone production to normal levels

relieve the pressure that the growing pituitary tumor may be exerting on the surrounding brain areas

preserve normal pituitary function or treat hormone deficiencies

improve the symptoms of acromegaly

Surgery

Surgery is the first option recommended for most people with acromegaly, as it is often a rapid and effective treatment. The surgeon reaches the pituitary via an incision through the nose or inside the upper lip and, with special tools, removes the tumor tissue in a procedure called transsphenoidal surgery. This procedure promptly relieves the pressure on the surrounding brain regions and leads to a rapid lowering of GH levels. If the surgery is successful, facial appearance and soft tissue swelling improve within a few days.

Surgery is most successful in patients with blood GH levels below 45 ng/ml before the operation and with pituitary tumors no larger than 10 millimeters in diameter. Success depends in large part on the skill and experience of the surgeon, as well as the location of the tumor. Even with the most experienced neurosurgeon, the chance of a cure is small if the tumor has extended into critical brain structures or into the cavernous sinus where surgery could be risky.

The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is normalization of GH and IGF-I levels. The overall rate of remission-control of the disease-after surgery ranges from 55 to 80 percent. (See For More Information to locate a boardcertified neurosurgeon.)

A possible complication of surgery is damage to the surrounding normal pituitary tissue, which requires lifelong use of pituitary hormone replacement. The part of the pituitary that stores antidiuretic hormone-a hormone important in water balance-may be temporarily or, rarely, permanently damaged and the patient may require medical therapy. Other potential problems include cerebrospinal fluid leaks and, rarely, meningitis. Cerebrospinal fluid bathes the brain and can leak from the nose if the incision area doesn't heal well. Meningitis is a bacterial or viral infection of the meninges, the outer covering to the brain.

Even when surgery is successful and hormone levels return to normal, people with acromegaly must be carefully monitored for years for possible recurrence of the disease. More commonly, hormone levels improve, but do not return to normal. Additional treatment, usually medications, may be required.

Medical Therapy

Medical therapy is most often used if surgery does not result in a cure and sometimes to shrink large tumors before surgery. Three medication groups are used to treat acromegaly.

Somatostatin analogs (SSAs) are the first medication group used to treat acromegaly. They shut off GH production and are effective in lowering GH and IGF-I levels in 50 to 70 percent of patients. SSAs also reduce tumor size in around 30 to 50 percent of patients but only to a modest degree. Several studies have shown that SSAs are safe and effective for long-term treatment and in treating patients with acromegaly caused by nonpituitary tumors. Long-acting SSAs are given by intramuscular injection once a month.

Digestive problems--such as loose stools, nausea, and gas--are a side effect in about half of people taking SSAs. However, the effects are usually temporary and rarely severe. About 10 to 20 percent of patients develop gallstones, but the gallstones do not usually cause symptoms. In rare cases, treatment can result in elevated blood glucose levels. More commonly, SSAs reduce the need for insulin and improve blood glucose control in some people with acromegaly who already have diabetes.

The second medication group is the GH receptor antagonists (GHRAs), which interfere with the action of GH. They normalize IGF-I levels in more than 90 percent of patients. They do not, however, lower GH levels. Given once a day through injection, GHRAs are usually well tolerated by patients. The long-term effects of these drugs on tumor growth are still under study. Side effects can include headaches, fatigue, and abnormal liver function.

Dopamine agonists make up the third medication group. These drugs are not as effective as the other medications at lowering GH or IGF-I levels, and they normalize IGF-I levels in only a minority of patients. Dopamine agonists are sometimes effective in patients who have mild degrees of excess GH and have both acromegaly and hyperprolactinemia-too much of the hormone prolactin. Dopamine agonists can be used in combination with SSAs. Side effects can include nausea, headache, and lightheadedness.

Agonist: A drug that binds to a receptor of a cell and triggers a response by the cell, mimicking the action of a naturally occurring substance.

Antagonist: A chemical that acts within the body to reduce the physiological activity of another chemical substance or hormone.

Radiation Therapy

Radiation therapy is usually reserved for people who have some tumor remaining after surgery and do not respond to medications. Because radiation leads to a slow lowering of GH and IGF-I levels, these patients often also receive medication to lower hormone levels. The full effect of this therapy may not occur for many years.

The two types of radiation delivery are conventional and stereotactic. Conventional radiation delivery targets the tumor with external beams but can damage surrounding tissue. The treatment delivers small doses of radiation multiple times over 4 to 6 weeks, giving normal tissue time to heal between treatments.

Stereotactic delivery allows precise targeting of a high-dose beam of radiation at the tumor from varying angles. The patient must wear a rigid head frame to keep the head still. The types of stereotactic radiation delivery currently available are proton beam, linear accelerator (LINAC), and gamma knife. With stereotactic delivery, the tumor must be at least 5 mm from the optic chiasm to prevent radiation damage. This treatment can sometimes be done in a single session, reducing the risk of damage to surrounding tissue.

All forms of radiation therapy cause a gradual decline in production of other pituitary hormones over time, resulting in the need for hormone replacement in most patients. Radiation also can impair a patient's fertility. Vision loss and brain injury are rare complications. Rarely, secondary tumors can develop many years later in areas that were in the path of the radiation beam.

Which treatment for acromegaly is most effective?

No single treatment is effective for all patients. Treatment should be individualized, and often combined, depending on patient characteristics such as age and tumor size.

If the tumor has not yet invaded surrounding nonpituitary tissues, removal of the pituitary adenoma by an experienced neurosurgeon is usually the first choice. Even if a cure is not possible, surgery may be performed if the patient has symptoms of neurological problems such as loss of peripheral vision or cranial nerve problems. After surgery, hormone levels are measured to determine whether a cure has been achieved. This determination can take up to 8 weeks because IGF-I lasts a long time in the body's circulation. If cured, a patient must be monitored for a long time for increasing GH levels.

If surgery does not normalize hormone levels or a relapse occurs, an endocrinologist should recommend additional drug therapy. With each medication, long-term therapy is necessary because their withdrawal can lead to rising GH levels and tumor re-expansion.

Radiation therapy is generally reserved for patients whose tumors are not completely removed by surgery, who are not good candidates for surgery because of other health problems, or who do not respond adequately to surgery and medication.

1 Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101(3):613-619.

2 Ayuk J, Sheppard MC. Growth hormone and its disorders. Postgraduate Medical Journal. 2006;82:24-30.


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## Nytol (Jul 16, 2005)

Thats a lot of reading!

Looks good though,


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## hackskii (Jul 27, 2003)

I saw some tidbits of info there that trigger GH output.


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## magneto12 (Mar 21, 2009)

As usual the medical establishement is trying to stop progress. Even after being proven to be very helpful in many ways HGH is still being fought and targeted harshly by the medical establishement and through lobying the government. They are claiming that HGH has many side effects but really doesnt everything; from too much sugar to any medication out there. If you take practically any medication and actually read the possible side effects you wonder how they even got these medications approved. My point is HGH probably has some side effects but don't its benefits far outweight the risks. HGH


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## Scotty-2-Hotty (Jan 13, 2009)

Very interesting.

I've got a few m8s that have ran courses of HGH, very expensive stuff, but with a lump of cash it can be retreived. One of my good mates who ran HGH and that is the only substance he has used, nothing else throughout his life (30 year old) and tbh he's massive, he told me he had no noticeable side-effects aside from the slight raise in the gut, which is one of the side effects the intestines expanding. Is there ways to prevent this?


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## Bazooka Tooth (Apr 7, 2009)

good article.

what iv read of it anyway


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## hackskii (Jul 27, 2003)

Scotty-2-Hotty said:


> Very interesting.
> 
> I've got a few m8s that have ran courses of HGH, very expensive stuff, but with a lump of cash it can be retreived. One of my good mates who ran HGH and that is the only substance he has used, nothing else throughout his life (30 year old) and tbh he's massive, he told me he had no noticeable side-effects aside from the slight raise in the gut, which is one of the side effects the intestines expanding. Is there ways to prevent this?


No, there is no way of preventing that.

There are sides, higher blood pressure, carpol tunnel syndrom (side effects that go away after discontinuence), mild insulin resistance, in some cases gyno symptoms, tingly fingers, hunger, to name a few.

Love the stuff myself though.


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## N2GB (May 23, 2008)

Wonder why I was drawn to this thread,I will be back to read in full later on this evening when I will have peace and quiet from the kids.

If I had added this thread it would have taken me the best part of a day to type it up


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## Van (May 22, 2009)

Thanks for that Hackskii im going to do some research on L-arginine powder and Ornithine as i know noth of these can be purchased but would like some people's user exerience for ''supplement effectivness''


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## bsbsbs (Aug 20, 2009)

well that was a nice read

so GH itself just makes the liver produce the igf-1 hormone which in turn has a rejuvenating effect on cells, but also makes everything grow which can be both a good and a bad thing

dont quite get the radiation therapy, how exactly can they target the pituitary gland without hitting anything in the area? :cursing:

also i didnt really read anything regarding amounts of igf-1, whats a good/bad value?...80 year olds having igf-1 levels of 40 year olds cant be that much of a bad thing


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## hackskii (Jul 27, 2003)

I have a couple of graphs on that one.


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## lewis66 (Jan 22, 2008)

Brilliant information!!!


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## TaintedSoul (May 16, 2007)

Now that's some reading material. Cheers Scott.


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## essexboy (Sep 7, 2008)

Scott, from reading the studies, it wolud appear that nasty sides such as high bp, are only evident from higher doses?


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## hackskii (Jul 27, 2003)

essexboy said:


> Scott, from reading the studies, it wolud appear that nasty sides such as high bp, are only evident from higher doses?


All sides are from higher doses.

Remember too, that us older guys seem to see the best benefits, most likely due to the decline in GH levels.

Below is a chart.

Hell, I will put up two.....lol

It also depends on the GH.

Chineese Generic Blue Tops were hands down the worst for sides I have ever seen.

Not sure why, may have been strong, not sure, I think Humatrope was hands down my favorite.

I do like Hyge though, I didnt like Saizan personally.


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## flatout.com (Jun 6, 2008)

hackskii said:


> All sides are from higher doses.
> 
> Remember too, that us older guys seem to see the best benefits, most likely due to the decline in GH levels.
> 
> ...


i've been using hyge for about 3-4 weeks and the pains in my wrists/forearms are savage (wakes me about 10 times a night).

bad headaches as well, may have to stop coz i love my sleep and after reading all the nasty stuff its made me really paranoid, knowing my luck i'm one of the minority thats get tumours.

if i fell in a barrel of tits i'd come out sucking my thumb


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## Need-valid-info (Mar 29, 2009)

do hgh injections shut down natural growth hormone release from a natty? If so is there a PCT for this?


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## Guest (Sep 28, 2009)

Need-valid-info said:


> do hgh injections shut down natural growth hormone release from a natty? If so is there a PCT for this?


Yes it does.

Time and perhaps stimulating drugs such as cjc and ghrp.

Overall it is nothing to worry about.


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## Need-valid-info (Mar 29, 2009)

thanks, i would probably try it if it wasnt so friggin expensive


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## hackskii (Jul 27, 2003)

This is the very reason why some dont shoot at night where nocternal release wont be supressed.


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## Chimpo (Apr 8, 2009)

I've used hydrotropin before, got on really well with it. Used it everyday, lost bodyfat and gained muscle mass. I used to inject by pinching the skin on my stomach. A friend just told me that you can inject into the muscle and you'll get more size gains by doing it this way. He also said you don't need to do it everyday, an someone shread some light on the situation for me please? thanks..


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## YoMamma (Dec 16, 2009)

Hello everyone, this my first post and I'm enjoying this Forum quite a bit.



> As usual the medical establishement is trying to stop progress. Even after being proven to be very helpful in many ways HGH is still being fought and targeted harshly by the medical establishement and through lobying the government. They are claiming that HGH has many side effects but really doesnt everything; from too much sugar to any medication out there. If you take practically any medication and actually read the possible side effects you wonder how they even got these medications approved. My point is HGH probably has some side effects but don't its benefits far outweight the risks. HGH/QUOTE]
> 
> Well here is my opinion about the media and Medical establishment.
> 
> ...


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## hackskii (Jul 27, 2003)

Nothing is perminant, I mean one has to constantly vary ones workout to keep the body guessing.

You will only stay as big as genetically you are supposed to.

Lets not forget that as we age, our hormones decline and muscle will be lost.


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## Thierry (Oct 19, 2009)

i've got a question about height and hgh, if plates are covered is there no chance of growth in length? i'm 19. alots been said about genes/genetics etc. and hgh, taking hgh will just get you to your limit sooner. if thats true then is it worth it, other than an increase in size sideway the cons of caveman doesn't sound appealing. would my doctor talk about this if i asked him?


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## fheb_21 (Jan 6, 2010)

HGH-hormone growth hormone

Is a best supplement because it has many functions and benefits in our body, just be sure that you are taking the right amount of supplement you are taking.


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## mal (Dec 31, 2009)

Chimpo said:


> I've used hydrotropin before, got on really well with it. Used it everyday, lost bodyfat and gained muscle mass. I used to inject by pinching the skin on my stomach. A friend just told me that you can inject into the muscle and you'll get more size gains by doing it this way. He also said you don't need to do it everyday, an someone shread some light on the situation for me please? thanks..


its been proven that eod ijections are the most effective way of using hgh.waste of money doing every day,2 iu when you wake up 2iu after training or bedtime,doses vary from 2 to 8ius some people take more.

Everyone has an opinion on this stuff.


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## 3752 (Jan 7, 2005)

fheb_21 said:


> HGH-hormone growth hormone
> 
> Is a best supplement because it has many functions and benefits in our body, just be sure that you are taking the right amount of supplement you are taking.


excellant so what are your thoughts on the correct dosing or how to work out the correct dosing?


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## hackskii (Jul 27, 2003)

mal said:


> its been proven that eod ijections are the most effective way of using hgh.waste of money doing every day,2 iu when you wake up 2iu after training or bedtime,doses vary from 2 to 8ius some people take more.
> 
> Everyone has an opinion on this stuff.


Proven?

Please enlighten us, I have used GH every day before and thought the results were very nice.

Many diffrent protocols and none seem to be better than any other one.

In fact to refute your statement, my friend had a daughter that had a disease and was perscribed HGH.

She took 2iu ED but not at night and she wasnt responding.

They changed her protocol to ED at night before bed and she grew 6" in 6 months.

So, with that said tell me how it works better when doctors perscribe it ED at night?


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## Cheese (Jul 7, 2009)

Bump for when i have a spare 3 days lol. Read half of the first article looks really interesting.


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## mal (Dec 31, 2009)

hackskii said:


> Proven?
> 
> Please enlighten us, I have used GH every day before and thought the results were very nice.
> 
> ...


 like i said everyone has an opinion about gh, it was proven in lab tests on mice,eod mice or rats cant rem grew bigger ,faster, and there was a reason for this i cannot rem ,maybe someone else can. Dude meds are perscribed at diff doses for many reasons,im no expert.people take gh every day cos they think more is better.


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## hackskii (Jul 27, 2003)

But I am familiar with the EOD dosing, it is double the ED dosing.

The 5 day on 2 off was designed to get around the whole insulin resistant thing.

The protocol I suggested comming from a doctor treating a growth defency, it was only effected when taken at night.

Now lets just look at this logically for one minute.

Biggest spurt of GH release aside from training is at night during R.E.M. sleep.

Makes sense to dose at night especially for us older folks when our levels are far below your levels.

Not to mention it is helpful for sleeping which helps in recovery and recouperation.

Many will not use at night due to it blunting endogenous GH production, and will use it in the morning to curb cortisol as that is the highest in the morning.

I noticed best fat loss was morning and afternoon shots.

I slept the best with night time jabs.

So, I dont feel there is any one best way unless you are older and to that, I would suggest at night before bed, but I dont believe any one way is better than another, unless we are talking about a growth defency which no doubt is best at night.


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## mal (Dec 31, 2009)

hackskii said:


> But I am familiar with the EOD dosing, it is double the ED dosing.
> 
> The 5 day on 2 off was designed to get around the whole insulin resistant thing.
> 
> ...


i agree with this, insulin. And thiroid problems to,for me low dose eod for me,morn and after training.4ius. :beer:


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## 3752 (Jan 7, 2005)

mal said:


> like i said everyone has an opinion about gh, it was proven in lab tests on mice,eod mice or rats cant rem grew bigger ,faster, and there was a reason for this i cannot rem ,maybe someone else can. Dude meds are perscribed at diff doses for many reasons,im no expert.people take gh every day cos they think more is better.


can you show us this study please?

i have used pretty much everyway you can use GH over the last 7yrs ED, EOD, split shots, all in one shots etc.....and i would definatly say that no one method is better than any other....

mice studies are great but they are not bodybuilders, our lifestyles change many things and would give different results than say a few caged mice but it would be good to see these studies...


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## super (Jan 9, 2010)

Hello im a new user ive been readin some stuff put on this site about growth i take 4iu evry otherday at night im just over 2 months in and ive noticed im not puttin weight on but not really noticing weight loss in the mirror any advice thanks Super


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## _Shaun_ (Mar 2, 2011)

Top thread!

I don't know much regarding HGH but I know Stallone makes loud noises regarding it's positive benefits.

After watching the "Rambo" movie from 2008 and I was hugely impressed with his physique - 209lbs, bodyfat around 7% and pushing 60, not bad at all.

I'm wondering if Brad Pitt's Dr didn't also prescribe him HGH for his role in the Troy movie a few years back, as prior to that movie he was a pencil necked wimp, then he appeared to miraculously gain at least 20lbs of lean mass for the Troy flick, only to resort immediately back to pencil necked wimp in his next movie.

Same with Orlando Bloom in the 'Kingdom Of Heaven' movie.


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## huge monguss (Apr 5, 2011)

Grate thread  Think I will have to read it Properly when I have a bit more time on me hands.


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## DiggyV (May 6, 2011)

Just found this thread, and is brilliant, thanks for the work compiling this Hackskii. Reps.

Being mid-40s myself, I am probably going to run hGH, but was wondering whether getting the 'generic' hGH (hyge?) from my source is OK, or whether to see if I can get hold of some norditropin pens? Is there any difference on the quality of these, or does it come down to the nortropin being more convenient, and not requiring the self mix / store problems?

Also any real benefits between sub-cutaneous and intra-muscular delivery?

Finally is there an optimal course length on the board's opinion?

Cheers

D


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## hackskii (Jul 27, 2003)

Sub-Q or IM makes no diffrence.

I have used hyge but not the pens.

I like hyge myself but like humatrope the best.

Many ways to use GH, 5 on 2 off, EOD, blast, it makes no difference, timing is debatable as well.


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## DiggyV (May 6, 2011)

Cool, thanks for the info very helpful.

Compared to the information about all things 20 years ago there is almost too much now, and trying to filter and distil it all is a great learning process, but sometimes just easier to go to the source. 

Cheers

D


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## hackskii (Jul 27, 2003)

DiggyV said:


> Cool, thanks for the info very helpful.
> 
> Compared to the information about all things 20 years ago there is almost too much now, and trying to filter and distil it all is a great learning process, but sometimes just easier to go to the source.
> 
> ...


Tell me about it, less than 10 years ago it was considered an advanced bodybuilding drug, now it is super common and one of my favorites of all things.

I remember one cycle with it I lost 4" on my waist, and 4 pounds of weight.

Love the stuff myself, I still believe though that the older guys tend to get the best benefits from it, due to our declining hormones.

Some life extension folks suggest it is the fountain of youth.

I do agree to some extent, a shot at night before bed and you sleep deeper with some pretty colorful dreams.... :lol:


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## DiggyV (May 6, 2011)

I know - PCT when I was first training was 1 amp of hcg (5000iu) the day after you stopped AAS, followed by a week on clomid! 

I am sold on hGH though. I am on holiday, sorry vacation, in 2 weeks time for 2 weeks, however I think I will be making some enquiries with my source, and getting an order in so it is ready for when I get back.

Will log my progress as well.

Slightly off thread if not topic. My wife has an under-active Thyroid so takes 125mcg per day. She is seeing sides on this though affecting hair, nails, skin, but if she takes less then she shuts down by 8:30 PM. Do you think that hGH might help counter some of the negative sides from prolonged Thyroxine usage? Curious is all...

Cheers,

D.


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## hackskii (Jul 27, 2003)

DiggyV said:


> I know - PCT when I was first training was 1 amp of hcg (5000iu) the day after you stopped AAS, followed by a week on clomid!
> 
> I am sold on hGH though. I am on holiday, sorry vacation, in 2 weeks time for 2 weeks, however I think I will be making some enquiries with my source, and getting an order in so it is ready for when I get back.
> 
> ...


Yah, I do, HGH interferes with that.

I thought low thyroid caused hair loss?

I know different endo doctors do different things with thyroid, some give you both T3 and T4, seems older people just dont process the T4 as well so the conversion is compromised.


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