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Growth Hormone Replacement Therapy (GHRT)
What is GHRT?

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Growth Hormone Replacement Therapy

Growth Hormone Replacement Therapy (GHRT)
What is GHRT?
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Growth Hormone Replacement Therapy (GHRT) is a regimen for treating physical and functional problems in people whose bodies, for one or more reasons, fail to produce adequate Human Growth Hormone (hGH).

GHRT is often a component of age management and Hormone Replacement Therapy (HRT) as hGH levels typically decrease with age, and restoration often delivers positive benefits for patients in conjunction with other HRT treatments.

Hallmarks of Aging: Decreased hGH, Muscle Mass, and Functional Capacity

 

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During development until young adulthood, muscle mass and strength
increase. After age 30, muscle mass and function begin to slowly decline. 

 

In both sexes, aging is accompanied by profound decreases in serum hGH and insulin-like growth factor-1 (IGF-1) concentrations. This is caused by reduced activity in the area of the brain that produces GH-releasing hormone (GHRH), the hormone that stimulates hGH production.  At the same time, somatostatin (SRIF) productions increases, which further inhibits hGH production.

Typically, hGH levels decline from their peak during puberty to about one-tenth of that value by age 55. Circulating hGH levels are lower and stimulated hGH is blunted during aging.

Defy Charts

   Spontaneous hGH Concentrations                                      Simulated hGH Concentrations

 

Feeling the Effects of Decreased hGH
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The physical effects of reduced hGH levels are felt in a variety of ways depending on the individual.

Reduction in the pattern of hGH sleep-related GH secretion resulting in loss of a clear night-day hGH rhythm.

The decline in GH production (age-related) results in a decline in body mass index and is associated with changes in body composition, hormonal status, and functional capacity that mimic the changes seen in GHD. 

Reduction in bone density, muscle mass and strength, parallel an increase in body fat and adverse changes in lipoprotein profiles are common.   The decline in hGH production is not evident initially but over time contributes to sarcopenia (severe loss of muscle) and frailty as aging advances.

Deterioration of memory and cognitive function is commonly reported with decrease in hGH.

Inactive individuals can lose up to 5% of their muscle mass per decade after age 30. Even those who remain active will experience some muscle loss.

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Loss of muscle mass accelerates significantly in middle age and beyond
regardless of physical activity, albeit more rapidly with inactivity. 

Adult-Onset GHD and Growth Hormone Insufficiency (GHI)
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Adult-onset GHD typically results from damage to the pituitary gland from medical issues such as tumors, surgery or radiotherapy that disrupt the gland’s ability to produce and secrete hGH.

GHI refers to the age-related decline in hGH production. This condition, along with its collective symptoms is known as somatopause, represents cessation of optimal secretion of hGH, which is similar to the decline of reproductive hormones that occurs during menopause in women and andropause in men.

 

Treatment of GHI with rhGH

Since age-related GHD is not associated with these causes, nor is aging generally considered a “disease”, there has been reticence to diagnose and treat declining growth hormone levels in the obese and in the elderly, to the levels it is treated in children and those suffering from adult-onset GHD. 

Thus, little attention was paid early on to treating the age-related progressive decline in hGH production that results in clinical symptoms similar to those associated with classic GHD.

For that reason, administration of rhGH, which is the accepted treatment for AGHD, has not been permitted for use in aging by the FDA.

This is true even though IGF-1, an indirect hormonal marker for hGH production and secretion, is indistinguishable in normal aging people after age 40 years from those with AGHD. 

Nonetheless, the FDA restricts diagnosis of GHD and treatment with rhGH to those under 40, and thereby requires different treatments for medical issues related to age-associated GHI. 

The Basics of Somatopause

Many of the body’s systems decline with advancing age making it more difficult to maintain optimal health and well-being.

Aerobic capacity, muscle mass, and strength all progressively decline as we age. Loss of muscle mass, or sarcopenia, and the accompanying reduction in strength increases the risk of falls and their complications. For many individuals, the associated loss of physical and functional capacity leads to increasing difficulty in living independently. 

Complaints of poor sleep are also common in older populations. Insomnia reduces quality of life and is often a factor in decisions to seek healthcare. Sleep complaints often lead to overmedication and sedation in the elderly that is often associated with increased morbidity and mortality. 

Finally, brain function declines with advancing age, particularly in those cognitive functions that involve novel problem-solving and psychomotor processing speed (an individual’s ability to process and respond to changes in their environment).  In turn, these deficits also impact an older individual’s ability to live independently.

Growth Hormone Secretagogues in GHI Treatment

Endocrine therapy treatments have been sought over the past two decades in response to the growing impact of GHI effects in the middle and later stages of life. There are a variety of pharmaceutical growth hormone secretagogues (GHSs) that are prescribed to increase growth hormone levels.

GHSs are a class of molecules that stimulate the secretion of hGH from the pituitary gland. They include stimulators of brain and pituitary receptors for GH-releasing hormone (GHRH) such as Sermorelin. 

Since GH secretion declines progressively and markedly with aging, and many age-related changes resemble those of adult-onset GHD, stimulating production and secretion of the body’s own hGH with GHRH or Sermorelin could confer benefits in normal aging like those observed by treatment with rhGH. 

In fact, many years of off-label use of Sermorelin have improved the life and health of many suffering from progressive and degenerative conditions of aging. 

This treatment could reduce the loss of muscle mass, strength, and exercise capacity that leads to frailty; thereby, potentially prolonging the ability to live independently. 

What is Growth Hormone Deficiency?
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Growth hormone deficiency (GHD) is the medical condition resulting from inadequate production and/or utilization of hGH.

GHD was initially observed in children, where it sometimes occurs because of problems in the brain and pituitary gland. Childhood-onset GHD significantly affects growth and development and causes medical problems and reduced quality of life.  Childhood-onset GHD has been treated with GHRT for more than 30 years.

Historically, hGH therapy in children with GHD was discontinued when the child reached their full height and bone growth ceased. The focus on height reflected a measure of successful GHRT therapy and. at the time, hGH was extracted from human cadavers making supply very limited.

Genetic advances made it possible to clone the gene that produced hGH in cell culture, which makes the recombinant form of human growth hormone (rhGH) widely available. Today, rhGH is the drug of choice, due to its broad availability, efficacy, and because it avoids the risk of transmitting a fatal virus that was associated with cadaver-derived hormone. 

 

Treating GHD in Adults

Although originally indicated for use in childhood GHD, in 1996 rhGH became a licensed indication for GH-deficient adults in the United States, several European countries, and New Zealand.

This action was taken because people who had been treated with rhGH as children and then were routinely discontinued from treatment upon reaching final height, experienced higher than expected rates of medical problems as adults, beginning in their 30s and 40s. 

These included reduced physical, mental, and social energy, excess adipose tissue, diminished muscle mass, diminished libido, poor bone density, higher than normal cholesterol levels, and elevated rates of cardiovascular disease.  Research trials soon confirmed that a few months of GH replacement therapy could improve nearly all these parameters in GHD patients. 

Coincidentally, it was noticed that the same changes in body composition and the increased risk for metabolic diseases also occur spontaneously as men and women grow older!

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