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 body’s pituitary gland. The only difference is that Somatropin is produced in a laboratory, using technology that copies the natural growth hormone molecule.

Product Administration
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 on self-administration for taking Somatropin by following this link: https://theantiagingdoctor.com/hGH_Injection_Procedures.pdf

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.

Side Effects
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.  

[Click to go to Brief Description of Hormone Function]

[Click 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; 86:545-550).
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: 147-161).

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; 12:152).

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 (PV) 5%.

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.

Conclusion
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].

Results
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 female patients.

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.

4. Correlation
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.

Discussion
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 and performance.

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 replacement’s 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.

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