Hormone Replacement &
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In order to understand why hormone balancing is important, you have to understand that
your body ages from the brain down; from the pineal gland, the control center, a pea-sized
computer in the center of the brain which releases melatonin, down to the hypothalamus
lying just behind the eyes at the base of the brain, which sends signals down to the
pituitary gland, a walnut sized outcroping extending below the hypothalamus which releases
growth hormone, thyroid stimulating hormone, follicle stimulating hormone and luteinizing
hormone (both necessary for female and male reproduction), prolactin (the milk producing
hormone and immune and testosterone suppressant), and adrenocorticotrophic hormone (ACTH),
which travels down from your pituitary to your adrenal glands to initiate the conversion
of cholesterol into all of your steroid hormones, including the intermediate adrenal
Therefore, the cascade down from the brain
affects the end organs: the thyroid and adrenal glands mentioned above, the ovaries and
uterus producing estrogen and progesterone, and the testes producing testosterone. In
return, the end organ hormones affect the brain through feedback mechanisms, and also each
other through biochemical conversion pathways. This can result in an imbalance from
inhibition of production, or an excessive production of one hormone overriding the
beneficial effects of one or more of the other hormones.
To offset aging and degeneration of your
hormonal system by replacement therapy, you need to replace hormones from the brain down
by balancing them in combination to ensure they all remain within youthful normal ranges.
Points of intervention, their hormones, and other chemicals that we know most about are
summarized in the table below.
The Lee-Benner Method to
Balanced Hormone Replacement
for the Clinical Age Management Program
Peripheral Neurons (Nerve Cells)
|Phosphatydil serine, DMAE, choline
Pregnenolone, ginko biloba, Acetyl-L-carnitine, pyroglutamic acid
Norepinepherine, Lipoic Acid
||Growth hormone, Chorionic gonadotrophin
|Calcium, Vitamin D
Arginine, Ornithine Zinc, Boron
The Limbic System
Heart, Bones, Joints
|Endorphin release through:
And finally, hormones, drugs,
nutrients and foods are all parts of the same single system of chemistry. Once you realize
this, the arguments about "natural" versus "unnatural" evaporate as
anti-science hype from unregulated "health food" pitchmen. The real question is:
"How much of a particular chemical, and when should I put it into my body for
successful Clinical Age Management?"
People considering hormone replacement
therapy need the guidance of a highly experienced neuro-endocrinologist to consider the
- What bodily hormones and other chemicals can benefit human
health when they are restored to youthful levels?
- If the form of the chemical is a man-made derivative of a
chemical that occurs in nature, does it match the natural form sufficiently to be
- What are the beneficial doses? Remember that any substance
you put into your body can have side effects. The dose of a substance frequently
determines whether it is beneficial or toxic to your system.
- What are the best ways to deliver these chemical substances
to the sites of action within the body, in the right dose, at the right time, and in a way
that does not interfere with normal homeostatic mechanisms of synchronized daily and
monthly rhythms of the myriad of body functions that are vital to your health?
There are profound biochemical differences between
individuals that can negate any conclusion drawn from the averages that result from
scientific studies of groups. Only your physician can obtain the correct testing and other
information required to estimate the unique needs of your individual physiology.
Human Growth Hormone
represent molecules in different ways depending on the information they need to review.
These pictures represent different ways of viewing the
Human Growth Hormone molecule, a complex structure consisting of a chain of 191 amino
Wireframe display of all atoms. Rotating image shows the complexity of
the molecule and its 3 dimensional structure.
Helix, sheet, and loop structures
This view breaks out the different amino acids by color.
The mucous membrane can pass molecules up to four amino acids
wide (four colored sections in the diagram).
It demonstrates how sublingual "hGH"
could not be absorbed, even if it were in the proper 3-D (folded) conformation that it
needs to be in order to work.
Click here for scientific information on human growth hormone from the
Protein Data Bank
Click here for structural information. Scroll down to the ATOM
records (left hand column is "ATOM"). Columns 6-8 are the 3 dimensional
coordinates of each atom in the hGH molecule.
for the main page of the Protein Data Bank
[Click Here to Go to
Features of Adult GH Deficiency
||Body Composition Function Body
composition shifts toward an increase in fat with a corresponding decrease in muscle. Bone
mineralization decreases. Vitality is lower both physically and psychologically. Increased
risk of dying from cardiovascular disease.
||Increased Cardiovascular Mortality Life
expectancy is shorter with acute GH deficiency, with long-standing pituitary failure,
inadequate replacement therapy and untreated GH deficiency.
||Abnormal Body Fat The
greatest increase in fact appears to occur in the abdominal and known to be associated
with a higher risk of cardiovascular mortality
||Dehydration Fluid loss amounted
to 10-15% of the extracellular fluid volume, equivalent to 4-6 pints.
||Low Bone Density - Bone mineral
densities are very low both in males and females.
||Psychosocial Deficit GH
deficiency shows psychological impairment and reduced quality of life. Tendencies towards
social isolation, poorer sleep, reduced physical mobility and emotional impairment.
Impaired Immune Function
GH deficiency is associated with a decline in the
body's production of natural killer (NK) cells. These are the cells responsible for
finding and destroying early mutations, which left unchecked, will eventually become
cancers. In this sense, growth hormone actually helps prevent the development of
cancer. It is a well known fact that the risk of cancer increases by a factor of
four with each decade.
Features of GH Replacement Therapy in Adults
Consistently Improved - Leaner body mass increase significantly, by a mean of 10.8%.
Decrease mean fat of 18.7%. Fat loss in the abdominal region. Leaner body mass increase
significantly, by a mean of 10.8%. Decrease mean fat of 18.7%. Fat loss in the abdominal
Lipolysis - Reduction
in body fat. Reduction in body fat.
Fluid Balance Restores
abnormal low levels of extracellular fluid. Normalizes kidney function.
Bone Density Increase
of bone mass, with the greater increase being in the vertebrae and forearm. Increases
connective tissue mass.
Exercise Capacity - Increases
the improvement in exercise capacity. Increase in skeletal muscle mass and strength.
Increase in cardiac output. Increases the improvement in exercise capacity. Increase in
skeletal muscle mass and strength. Increase in cardiac output.
Improved Quality of Life
Less fatigue and greater stamina. Increased physical performance. Improved mind
and sexual function.
Improved Immune Function
Growth Hormone stimulates the production of natural killer (NK) cells which
destroy pre-cancerous mutations.
Somatropin [rDNA origin] for Injections
Somatropin is a generic name for human growth
hormone replacement therapy for individuals who do not produce enough growth hormone of
The human body produces many different
kinds of hormones-one of which is growth hormone. Hormones are made by glands and are
secreted into the bloodstream to stimulate other parts of the body to perform specific
activities. For example, the pancreas produces the hormone insulin, and the ovaries
produce the hormone estrogen.
Somatropin is exactly like the natural
growth hormone produced by the bodys pituitary gland. The only difference is that
Somatropin is produced in a laboratory, using technology that copies the natural growth
Somatropin is given by subcutaneous injection-that is, with a tiny, insulin needle
injected just below the skin. This "injection" method is necessary because
growth hormone is made of the same type of protein found in foods. If Somatropin were
taken by mouth, it would be digested in the stomach and become inactivated. An
"injection" of Somatropin allows it to get directly into the blood stream,
avoiding digestion in the stomach. In this way, the growth hormone remains active to
contribute its normal metabolic effects.
Injections of Somatropin are relatively
easy to give. Follow the steps in the handout provided to you at the end of your office
consultation on self-administration for taking Somatropin.
Your dose will be individualized for you.
If you took growth hormone as a child, you will be reevaluated for your need to take it as
an adult. If continued treatment is appropriate, your adult dose will be smaller than the
one you used as a child.
Serious side effects do not usually occur. In studies of adults with growth
hormone deficiency, the most common side effects were mild to moderate symptoms of fluid
retention, swelling of extremities, painful joints, pain, and stiffness of the
extremities, muscle pain, an abnormal sensation (such as burning or prickling), or an
abnormal decreased sensitivity to stimulation. By dividing your daily dosage in half, and
taking one half in the morning and one half just before bedtime, you will reduce the
possibility of developing any of the above side effects. The best time to administer
really depends on your schedule. Try to give it at the same time each day, at a time when
you are not rushed.
Somatropin should be stored under
refrigeration. (Do not freeze.)
If for some reason your vial of Somatropin
is left outside a refrigerator for an extended length of time, contact my office for
instructions before using.
The Benefits of hGH Treatment
Low dose (rDNA) hGH normalizes bone metabolism and improves bone density in adults
without causing adverse effects.
9 GH deficient adults, 7 males and 2 females (aged 25-34 years) were studied
during 12 months of hGH treatment of subcutaneous injections twice daily at physiologic
Serum IGF-I, IGFBP-3,
bone GLA protein, procollagen-III, parathyroid hormones (PTH), vitamin D and bone mineral
density at proximal and ultradistal sites of the radius were measured.
Before treatment all
the levels measured were significantly lower than in controls. GH therapy normalized all
these parameters except for the distal value, which nonetheless increased. No significant
changes in PTH and vitamin D variation were seen. After 12 months of hGH therapy, all
parameters returned to pretreatment values.
12 months of hGH
treatment at the lowest doses so far used normalizes bone metabolism and cortical bone
density, and improves trabecular bone density without causing adverse effects.
[Click to go to Brief
Description of Hormone Function]
to See One Patient's Results]
Growth Hormone &
IGF Research 2002
Cortisol in the presence of insulin, activates Lipoprotein Lipase (LPL), which is a
main regulator of triglyceride assimilation in adipose tissue. (Metabolism 1990;
30:1021-1025). In support of this, the specific glucocorticoid and progesterone receptor
antagonist, RU-486, inhibits cortosol-induced LPL expression in human adipose tissue.
(Obes. Res. 1995; 3:233-240). LPL activity is higher in visceral than in subcutaneous
adipose tissue (J Clin Endocrinol Metab 1995; 80:936-941.)
According to a recent study, an increase in evening cortisol levels is present after
midlife in men, whereas the morning values show no age-dependent change (JAMA 2000: 284:
861-868.) In addition, it is thought that there is a subtle change in the sensitivity of
the HPA axis with aging (Aging Milano 1997; 9: 19-20.) Studies in humans suggest that
there is an age-related decline in the resilience of the HPA axis, leading to
progressively greater exposure to glucocorticoids (J Clin Endocrinol Metab 2001;
Two factors might facilitate this process:
1. The age-related decrease in brain corticosteroid receptors leads to a decrease in the
hypothalamic-pituitary sensitivity to negative feedback from glucocorticoids;
2. Repeated cortisol-generating stress challenges.
Dexamethasone (DEX) inhibition on peripheral cortisol concentration has a reduced response
of the HPA axis to DEX with aging; higher mean cortisol levels of post-DEX were observed
in the elderly. Recently published data noted that a dose of 1mg DEX is too high to detect
individual differences in feedback sensitivity within a normal population, since near
total suppression occurred in most individuals (J CLin Endocrinol Metab 1998;83:47-54).
Low Dose Dexamethasone Suppression Test
A control 8am plasma and a 24 hour urine-cortisol with creatinine are obtained, followed
by low-dose DEX 10µg/kg/max 0.5mg) every 6 hours for 2 days. Plasma cortisol and
creatinine are obtained on the second day of DEX. On day 3, collect 8am blood sample for
cortisol level. Normal responses are suppression of plasma cortisol <5µg/dl and
suppression of urine free cortisol to <20µg/24h.
Combined role of cortisol, insulin and GH at the adipose tissue site.
Cortisol and insulin facilitate lipid accumulation, particularly in the visceral adipose
tissue, whereas GH causes lipolysis. GH inhibits LPL expression induced by cortisol and
insulin; and lipolysis is increased. This makes teleological sense, since the main
metabolic effect of GH is the protection of LBM (protein) during times of energy deficit
(fasting). To prevent protein utilization GH increases lipolysis, fatty acid utilization
and non-oxidative glucose disposal. Dexamethasone down regulates expression of a factor:
Pref-I (preadipocyte factor1) which blocks differentiation of adipocytes, while GH
prevents its down regulation in preadipocytes. The net effect is glucocorticoids
facilitate and GH inhibits differentiation of adipocytes.
Increased glycocorticoid levels lead to inhibition of protein synthesis, as well as
inhibition of amino acid transport into muscle. DEX blunts BCAA--stimulated
phosphorylation of key proteins (IF4-BP1and p70S6K) involved in activating the mRNA
translation apparatus. This may explain the catabolic effect of glucocorticoids on protein
metabolism in skeletal muscle. Glucocorticoids also cause resistance to the
antiproteolytic effects of insulin in muscle. Short-term high dose Predisone also leads to
a negative leucine balance in both the fasted and fed state(GH and IGF-I Res 2002; 12:
Several studies suggest that these cortisol-related effects on body proteolysis may be
prevented by GH. Fry, et al, showed that GH increases protein synthesis in forearm tissue
within 6-8 hrs of intra-arterial infusion and GH compensates for the nitrogen losses
induced by glycocorticoids by increasing protein synthesis (GH and IGF-I Res 2002;
Since both cortisol and GH increase peripheral tissue resistance to insulin, this may be a
relative obstacle to the use of GH to prevent cortisol induced catabolism. However, this
likely is dose related and it is unclear what dose of GH is necessary to minimize the
catabolism of physiological concentrations of cortisol.
Growth Hormone &
IGF 2003 Updates
Effects of GH on Body Fluid Balance
Approximately 60% of body weight is water. Total Body Water (TBW) is subdivided into
intracellular volume (ICV), 40% predominated by the cation and anion potassium and
phosphate, respectively, and extracellular volume (ECV) 20% dominated by sodium and
chloride, which is further subdivided into interstitial volume (IV) 15% and plasma volume
Measurement of body fluids suffers from a lack of a gold standard method. As a
consequence, many different methods have been developed, which are difficult to compare.
Despite differences in estimating these body fluid compartments, most authors seem to
agree that body fluid volume is decreased in GH-deficient adults, and that GH treatment
normalizes body fluid volume in these patients. There is also agreement that GH causes
volume expansion, when administered in pharmacological doses to normal subjects and when
secreted in excess in active acromegaly (Giantism).
Evaluation of fluid status in GH-deficient patients is complicated by the fact that some
patients suffer from additional pituitary deficits such as ACTH, gonadotropins, and TSH
potentially influencing body fluid compartmental balances. In addition, secretion of
another hormone from the pituitary gland, Vasopressin, may be impaired. Although the
problem may be reduced by optimal substitution of all pituitary hormones, the potential
differences of this group of patients should be kept in mind when assessing the effect of
GH on body fluid balances (Homeostasis).
A common side effect to GH administration are symptoms and signs of fluid retention, which
seem to occur mainly during the initial phase of treatment [Jorgensen, et al, Lancet I
(1989) 1221-1225 and Cuneo et al. Clin. Endocrinol. (Oxf) 37 (1992) 387-397]. In a more
recent study full normalization of ECV compared to a normal control group was obtained
only after 3 weeks of administration [Moller, Growth Hormone & IGH Research 13(2003)
55-74]. These data indicate that the symptoms of fluid retention often encountered by
GH-deficient patients during the first days of treatment probably is related to the
changes in fluid distribution rather than absolute overhydration.
GH causes volume expansion and transient sodium retention without affecting PV in normal
man when administered in pharmacologic doses. Volume expansion following GH administration
has been demonstrated in catabolic (wasting-syndrome) patients. Some data suggest this to
be a beneficial effect, since intracellular dehydration has been demonstrated to correlate
well with the degree of protein loss during critical illness. In addition, vascular volume
optimization improves outcome after various surgical procedures.
GH deficiency is associated with decreased TBW, ECV, ICV and PV. Extracellular volume and
in particular PV are important for measurement of cardiovascular function such as mean
arterial pressure and left ventricular filling volume [Miller et al. The Kidney. WB
Saunders. Phil 1996, pp. 817-872].
Intracellular dehydration has been suggested to trigger protein breakdown, and cell
swelling stimulates protein formation [Hausinger et al. Lancet 341 (1993) 1330-1332].
Thus, a normalization of the internal environment (ECV and PV) and ICV should in theory be
beneficial to GH-deficient patients, and, in fact, this does occur following GH
replacement. It could be speculated that the improvements in cardiac and renal function,
and in protein and lipid metabolism seen during GH replacement could be at least partly
due to normalization of body fluid balance (homeostasis).
Consequently, the fluid and sodium-retaining effect of GH should be regarded to represent
a physiological normalization rather than an unpleasant side effect. The extracellular and
plasma volume expanding effect of GH excess is clearly seen in acromegalic patients. It
seems reasonable to speculate that a number of distinct symptoms such as carpal tunnel
syndrome, headache and parasthesias are related to volume expansion due to excessive GH
secretion in acromegalic patients.
Effects of GH replacement therapy on metabolic and cardiac parameters in adult patients
with childhood-onset GH-deficiency. (16 patients age between 18 and 35 years) [Jallad et
al. Growth Hormone & IGF Res. 13 (2003) 81-88].
1. Hormone and Metabolic Values
After 6 months of GH replacement, IGF-I was normal for age and sex in 15 patients and
remained reduced in only one patient, whereas IGFBP-3 was normal in 6 and remained reduced
in ten patients. After 12 months of GH-therapy, IGF-I was normalized in all patients,
whereas IGFBP-3 was normal in 10 and still reduced in six patients. The serum
concentration of IGF-I before and after replacement therapy did not differ between male
and female patients. A decrease in total cholesterol and LDL/HDL-cholesterol ratio was
detected during the GH-therapy period in comparison with that at basal levels. Despite the
tendency toward increased insulin values during GH-replacement, no statistical differences
between before and during the GH therapy period were noted, parallel to no variation in
fasting serum glucose and glycated hemoglobin levels.
2. Body Composition
A significant increase in lean body mass and concomitant and similar decreases in fat body
mass were observed after 12 months of GH-therapy, without a significant change in body
weight. No differences regarding body composition could be observed between male and
3. Cardiac Parameters
Echocardiographic results: before treatment, patients had significant decreased left
ventricular (LV) mass, such as interventricular septal thickness, LV posterior wall
thickness and LV mass index, compared with those in healthy control subjects. After 12
months of therapy, all these indexes had significant increases, and had no more
significant differences compared with those in normal control subjects.
Treadmill exercise test results: All exercise tests were negative for myocardial ischemia.
At baseline, 5 patients had submaximal tests (because of leg weakness or exhaustion).
After 6 months of GH replacement, only one patient had a submaximal test, and after 12
months all had maximal tests (95% of age-predicted maximum heart rate). Between pre- and
post- treatment, the patients had notable improvement in exercise performance, such as
increased exercise duration, double product, and estimated peak oxygen uptake consumption.
Only a discreet correlation was found between LV mass index and exercise duration after 12
months with GH replacement treatment.
5. Clinical Tolerance
When comparing pre-treatment with 12 months of GH-replacement, resting arterial systolic
blood pressure (106.3 plus or minus 11.5 mmHg x 111.3 plus or minus 10.8 mmHg) and
diastolic pressure (68.1 plus or minus 7.5 mmHg x 70.6 plus or minus 6.8 mmHg) had
no significant changes. Some previous studies observed that by using doses of GH based on
body weight or body surface, side effects are more prone to occur, associated mainly with
fluid retention [Johannsson, et al. Clin. Endocrinol (Oxf) 47 (1997) 571-581]. In the
present study, two women and four men reported mild arthralgia, particularly in the hands,
knees, and feet, and peripheral mild edema, in the beginning of treatment and that
disappeared with continual therapy. When the patients visited the clinic for physical
examination and assessment after 3 months of therapy, no side effects were seen. No
patient withdrew from treatment because of side effects. All patients had good adherence
to GH replacement therapy.
A current consensus indicates that diagnosis of GH deficiency (GHD) in the presence of
pituitary deficiencies requires a single dynamic test to confirm it in adult life
[Consensus guidelines for the diagnosis and treatment of adults with growth hormone
deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult
Growth Hormone Deficiency. J Clin. Endocrinol. Metab. 83 (1998) 379-381]. Increasing
degrees of anterior pituitary failure predict a high probability of GHD, and when two or
more hormone deficiencies are present, the possibility of GHD is very high [Toogood, et
al. Clin. Endocrinol. (Oxf) 41(1994) 511-516].
IGF-I levels are not consistently low in patients with GHD of adult-onset. In fact, normal
IGF-I levels were reported in 73.3% of patients with partial GHD, and in 29.2% of patients
with very severe GHD [Colao, et al. J. Clin. Endocrinol. Metab. 84 (1999) 1277-1282]. Thus
IGF-I may be a more useful guide to GH status only in younger adults (ages 18-35) who have
childhood-onset severe GH deficiency.
A dose titration regimen of GH replacement based upon achieving and then maintaining IGF-I
levels above the median level, but below the upper limit of the age-related reference,
rapidly obtaining effective but lower maintenance doses of GH, minimizing the potential
adverse effects of GH treatment have been suggested [Johannsson, et al. J Clin.
Endocrinol. Metab. 81 (1996) 1575-1581; Johannsson, et al. Clin. Endocrinol (Oxf) 47
(1997) 571-581; Drake, et al. J. Clin. Endocrinol. Metab. 83 (1998) 3912-3919].
GHD is associated with cardiac risk factor indices such as abnormal circulating lipid
profile, body composition with increases in total body fat, central obesity, and decreases
in lean body mass, and cardiovascular abnormalities. There is growing evidence that
treatment with GH can ameliorate lipids and body composition, as well as reverse most of
the cardiovascular abnormalities associated with childhood and adult onset GHD. [Ter
Maaten, et al. J. Clin. Endocrinol. Metab. 84 (1999) 2373-2380; Gibney, et al. J. Clin.
Endocrinol. Metab. 84 (1999) 2596-2602; Colao et al. J. Clin. Endocrinol. Metab. 87 (3)
(2002) 1088-1093]. The reduced cardiac death after GH replacement therapy could be due
mainly to reducing cardiovascular risk factors more than improving the cardiac structure
The minimum period of treatment for ideal correction of heart indexes seems to be 12
months. However the changes, especially in performance and strength are very subtle and
occur over long periods of time. Data from Jorgenson indicates that about 36 months is
required before they begin to respond as measured by exercise capacity [Jorgenson, et al.
Eur. J. Endocrinol.130 (1994); 224 fig 1]. Because cardiac indices appear to return to
pretreatment values after some months of GH replacements interruption [Amato, et al.
J. Clin. Endocrinol. Metab. 77 (1993) 1671-1676; Valcalvi, et al. J.Clin.
Endocrinol.Metab. 80 (1995) 659-666; Colao, et al. J. Clin. Endocrinol. Metab. 87 (2002)
1088-1093], it is widely believed that a permanent dosage of GH replacement seems to be
imperative. More long-term trials are needed to confirm these benefits and to determine
the ideal dosages to be used in long-term GH replacement therapy of GHD.
& IGF Update 2004-2009:
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View: Growth Hormone -- Adult Deficiency
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Effects of Growth Hormone on Visceral Fat and Obesity
Here to View: Current Concepts of Estrogen Regulated Secretion
on Menopausal Women
Here to View: AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR GROWTH HORMONE USE IN GROWTH HORMONE-DEFICIENT ADULTS AND TRANSITION PATIENTS – 2009 UPDATE
& IGF Update 2010:
Here to View: Understanding Causes and Comorbidities for Accurate Diagnosis
and Patient Selection for Treatment of Adult Growth Hormone Deficiency: An
Here to View: Practice AID -- Diagnostic Procedures for Transition & Adult
Patients With GHD
Sex Hormone *
Adrenal Gland Extracts *
Pineal Gland Extracts *
* Medical Physician's supervision required
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