HUMAN GROWTH HORMONE RESEARCH & NEWS

Description:

Lyophilized Powdered Genotropin contains Recombinant-DNA [rDNA] derived somatropin. Somatropin is a polypeptide hormone comprised of a chain of 191 residues of amino acid, and it has a molecular weight o 22,124 daltons. Somatropin's sequence of amino acids is exactly the same as that of Human Growth Hormone which originates in the pituitary gland. Genotropin is created through a modification of a particular strain of E. coli to include the gene that is responsible for Human Growth Hormone. Genotropin comes in the form of a white, sterile powder, lyophilized and intended for injection subcutaneously.

Genotropin 1.5 milligram is administered using a 2-chambered cartridge. The front compartment holds 1.5 milligrams of rDNA-derived somatropin (about 4.5 IU), 27.6 milligrams of glycine, 0.3 milligrams or anhydrous sodium dihydrogen phosphate, and 0.3 milligrams of anhydrous disodium phosphate. The rear compartment holds 1.13 milliliters of water used for injection.

Genotropin 5.8 milligram is administered using a 2-chambered cartridge. The front compartment holds 5.8 milligrams of rDNA-derived somatropin (about 17.4 IU), 2.2 milligrams of glycine, 1.8 milligrams of mannitol, 0.32 milligrams of anhydrous sodium dihydrogen phosphate, and 0.31 milligrams of anhydrous disodium phosphate. The rear compartment holds 0.3 percent m-Cresol for use as a preservative, along with 45 milligrams of mannitol and 1.14 milliliters of water to be used for injection.

Genotropin 13.8 milligram is administered using a 2-chambered cartridge. The front compartment holds 13.8 milligrams of rDNA-derived somatropin (about 41.4 IU), 2.3 milligrams of glycine, 14.0 milligrams of mannitol, 0.47 milligrams of anhydrous sodium dihydrogen phosphate, and 0.46 milligrams of anhydrous disodium phosphate. The rear compartment holds 0.3 percent m-Cresol for use as a preservative, along with 32 milligrams of mannitol and 1.13 milliliters of water to be used for injection.

Genotropin Miniquick is administered by a one-time use syringe device that holds a 2-chambered cartridge. Genotropin Miniquick, can be attained in single doses varying from 0.2 milligrams to 2.0 milligrams in increments of 0.2 milligrams. The front compartment holds 0.22 to 2.2 milligrams of rDNA-derived somatropin (about 0.66 to 6.6 IU), 0.23 milligrams of glycine, 1.14 milligrams of mannitol, 0.05 milligrams of anhydrous sodium dihydrogen phosphate, and 0.027 milligrams of anhydrous disodium phosphate. The rear compartment holds 12.6 milligrams of mannitol in 12.6 milliliters of water to be used for injection 0.275 milliliters.

Genotropin is prepared in a highly purified manner. The recombinant reconstituted solution of somatropin has an pH of about 6.7 and an osmolality of about 300 mOsm/kg. Concentration of the somatropin solution is dependent upon the presentation and strength (read more in the section How Supplied).

Clinical Pharmacology

Clinical, preclinical, and in vitro tests show that Powdered Lyophilized Genotropin is equivalent to Human Growth Hormone that originates naturally in the pituitary in terms of therapeutic results.

The body reacts in a similar fashion to Genotropin as it does to the Human Growth Hormone created internally in the average adult. Genotropin therapy in child patients who suffer from a growth hormone deficiency (GHD) succeeds in stimulating normal growth and balances concentrations of Somatomedin-C/Insulin-like Growth Factor (IGF-1). Genotropin treatment in adults who are maligned with Growth Hormone Deficiency often results in a lower level of body fat, an increased amount of lean muscle mass, and changes in metabolism that include positive changes in the metabolism of lipids and the balance of concentrations of IGF-1.

Also, many other results have been shown through the administration of somatropin and/or Genotropin, including:

Tissue Growth

Skeletal System Growth: Genotropin has been shown to stimulate the growth of the skeletal system in young patients who suffer from Growth Hormone Disorder. There is a significant increase in the length of the body through the use of Genotropin that results from its effect upon the epiphyseal plates which develop inside the long bones. Serum levels of Insulin-Like Growth Factor-1, which likely play a part in the growth of the skeletal system, are found to usually be quite low in young patients suffering from Growth Hormone Disorder. These levels increase when the patient undergoes Growth Hormone Replacement Therapy with Genotropin. Higher serum concentrations levels of alkaline phosphatase also are seen with treatment.

Cell Growth: Research has shown that young, short-statured children have a lesser number of skeletal muscle cells because they have an insufficient level of natural Growth Hormone in comparison to the normal child population. Treatment with Genotropin leads to a boost in both the size and number of these muscle cells.

Protein Metabolism

Linear, normal growth in childhood is in part facilitated through an increase in the synthesis of cellular proteins. Retention of nitrogen, which is shown through a decrease in the excretion of nitrogen through urination, as well as through blood test measurements of nitrogen in the urea, is one of the many physiological changes that occur through Genotropin therapy.

Carbohydrate Metabolism

Children who suffer from hypopituitarism often also experience hypoglycemia when fasting, and this issue is also alleviated through Genotropin treatment, though excessive doses of Human Growth Hormone can lead to glucose intolerance.

Lipid Metabolism

In those who are deficient in Growth Hormone, Genotropin therapy has been shown to result in the mobilization of lipids, allowing for a reduction in storage of body fats and a higher level of fatty acid in the plasma.

Mineral Metabolism

Genotropin also can lead to a retention of phosphorus, potassium, and sodium. Concentrations of inorganic phosphate in the blood stream are also increased in those patients maligned with Growth Hormone Disorder who go through Genotropin Hormone Therapy. Levels of calcium in serum are not changed in a significant manner through the use of Genotropin, and Human Growth Hormone can lead to calciuria.

Body Composition

Adult patients who suffer from Growth Hormone Disorder that are treated with Genotropin at the suggested adult dosage (view Dosage and Administration for more information) show a decreased level of body fat and an increased level of lean muscle mass. These changes occur at the same time that the body begins to retain fluid more effectively. The result of all of this is that Genotropin has the ability to positively modify the composition of the body, and these positive changes can be sustained through continuing treatments.

Pharmakonetics

Absorption

After delivering a 0.03 milligram/killigram subcutaneous (abbreviated SC) thigh injection of 1.3 milligram/milliliter Genotropin to an adult patient with Growth Hormone Disorder, around 80% of the total dose was available for usage by the body in comparison to that available to the body through an intravenous dose. The results were similar in both female and male hormone replacement therapy patients, and a similar level of bioavailability has been shown in healthy male adult subjects as well.

In adult healthy males, after a subcutaneous thigh injection of 0.03 mg/kg, the extent of AUC absorption of a 5.3 mg/ml concentration of Genotropin proved to be 35% higher than that from 1.3 mg/mL Genotropin. The mean (plus or minus standard deviation) peak (max C) serum levels were 23.0 (plus or minus 9.4) ng/mL and 17.4 (plus or minus 9.2 ng/mL, respectively.

In another study of a similar kind with pediatric Growth Hormone Deficiency patients, dosage of 5.3 mg/mL Genotropin produced a mean area under the curve that happened to be 17% higher than the mean AUC for 1.3 mg/mL Genotropin. The mean max C levels were 21.0 ng/mL and 16.3 ng/mL respectively.

In yet another study, Adult GHD sufferers were administered two separate subcutaneous doses of 0.03 mg/kg Genotropin at a 1.3 mg/mL concentration. There was a 1-4 week period to washout between the injections. The mean max C levels were 12.4 ng/mL for the first administration and 12.2 ng/mL for the second injection, and this was reached at around 6 hours after the dose was received.

No data exists regarding bioequivalence between the 12 mg/mL dosage and the 1.3 mg/mL or the 5.3 mg/ml doses.

Distribution

The mean distribution volume of Genotropin after it has been administrated to adults with Growth Hormone Deficiency was figured to be about 1.3 (plus or minus 0.8) L/kg.

Metabolism

Genotropin is metabolized in through normal protein catabolism which occurs in both the kidneys and the liver. In the kidney cells, some of the products of Genotropin's breakdown are filtered back into the circulation of the system. The terminal mean half-life of Genotropin which is administered intravenously in a normal adult is around 24 minutes, but when Genotropin is administered subcutaneous, it has a half-life of 180 minutes in adults with Growth Hormone Disorder. This significant difference in half-life is due to the fact that when Genotropin is administered subcutaneous it absorbs into the body at a much slower rate.

Excretion

The mean of clearance or excretion of Genotropin which has been administered subcutaneously in a study of 16 adult subjects with Growth Hormone Disorder was 0.3 (plus or minus 0.11) L/hrs/kg.

Special Populations

Pediatric: Genotropin is broken down in adults in a similar manner as it is broken down in children.

Gender:There have been no studies that attempt to differentiate the difference in effect that Genotropin has between young boys and young girls, but it should be noted that Genotropin bioavailability has been found to be similar between adult female's undergoing Growth Hormone Replacement Therapy and Male Hormone Replacement Therapy patients in regard to Growth Hormone Deficiency.

Race:No research has been conducted with regard to whether race plays a factor in the pharmacokinetic results of Genotropin use.

Hepatic or renal insufficiency: There have been no research studies conducted in regard to Genotropin's effect on these particular populations of patients.

Table One

Average subcutaneous pharmacokinetic parameters of adult patients who are deficient in Growth Hormone.

Bio-availability

(percentage)

(Number of participants = 15) Max T

(Time [hours])

(Number of participants = 16) Clearance Rate

(Liters/hour ' kilogram)

(Number of participants = 16) Vol.Dis.

(Liters/kilogram)

(Number of participants = 16) T

(hours)

(Number of participants = 16)

Average 80.5 / 5.9 / 0.3 / 1.3 / 3.0

( St.Dev.) * ( 1.65) ( 0.11) ( 0.80) ( 1.44)

95% CI 70.5 to 92 /. 5.0 to 6.7 / 0.2 to 0.4 / 0.9 to 1.8 / 2.2 to 3.7

Max T= Time that has elapsed when plasma concentration peaks

Clearance Rate = rate in which Genotropin is excreted from the body

Vol/Dis = distribution volume

T = time that it takes the plasma concentration of Genotropin to reduce by half from its peak

St.Dev. = standard deviation

Cl = interval of confidence

Absolute Genotropin bioavailability has been estimated with the assumption that the data which has been transformed by log will follow a normal, standard distribution. The standard deviation and mean of the transformed were a mean of 0.22 and a standard deviation of plus or minus 0.241.

Clinical research with adult Growth Hormone Disorder patients

Lyophilized Genotropin Powder was tested along side a placebo in 6 clinical randomized trials which involved 172 adult Growth Hormone Disorder patients in total. The trials featured a six month treatment period which was double-blind in nature. During this period, 85 participants were administered Genotropin and 87 participants were administered a placebo. After this, an open-label period of treatment followed. During this period, patients who chose to participate were administered Genotropin for a period of time as long as 24 months.

Genotropin was injected subcutaneously each day with a dosage of 0.04 mg/kg dose of 0.04 mg/kg/wk during month one of treatment and in the subsequent months thereafter it was administered at 0.08 mg/kg/wk

After the six-month period of treatment, researchers looked for changes that were beneficial to the composition of the body for both the group that received Genotropin injections as well as the group which received injections of placebo. It was found that in the Genotropin group lean muscle mass, total water retention, and the ratio of lean/fat improved, while circumference of the waist and total mass of body fat reduced to more healthy levels. The effects of Genotropin on the composition of the body were retained with those who pursued treatment past the initial six month period. Mineral bone density began to decline after six months of treatment, but after twelve months of treatment the density values returned to baseline.

Usage and Indications

Lyophilized Genotropin Powder is designed for long-term therapy of pediatric patients that suffer from growth failure as a result of the inadequate production of endogenous Human Growth Hormone. It is not recommended for other causes of short stature.

Genotropin is also designed for long-term Growth Hormone Replacement Therapy for adults that suffer from a Growth Hormone Deficiency that is of either adult or childhood-onset in its etiology. Growth Hormone Disorder should be diagnosed through an appropriateGrowth Hormonestimulation test.

Contraindictions

Lypophilized Genotropin Powder should not be used if an individual shows any signs of neoplastic activity. Intracranial spade occupying lesions must be inert and antitumor treatment must be complete before Genotropin therapy begins. If the tumor begins to grow again, Genottropin treatment should be discontinued immediately. Also,Growth Hormoneshould no be administered as a means to promote growth in children who have fused epiphsys in the long bones.

Human Growth hormone treatments should not be administered to provide therapy for individuals who have an acutely critical illness stemming from abdominal or open heart surgery, multiple physical accidental trauma, or to those who have suffered acute respiratory failure.

A pair of clinical research trials involving 522 total adult participants that showed no signs of Growth Hormone Deficiency who suffered from these conditions were conducted. The results of these two studies revealed that there was a significantly higher incidence of mortality (41.9% vs. 19.3%) affecting those who were treated with somatropin (5.3 to 8 mg/day dosage) in comparison to those that merely received placebo (read Warningsfor more information).

Warnings

The 13.8 mg and 5.8 mg preparations of Lyophilized Genotropin Powder contain the preservative m-Cresol. Those who have a sensitivity or allergy to this preservative should not use these products. The Genotropin Miniquick and Genotropin 1.5 mg preparations do not have m-Cresol, or any preservative (Read the How Supplied section for more information).

Read the Contraindictions section for more information about increased mortality risk in those who suffer from critical illnesses in ICU because of complications due to abdominal or open heart surgery, multiple trauma due to an accident, or those who are suffering from acute respiratory failure. The proper research has not been established regarding the safety of continuing to undergo Growth Hormone Replacement Therapy for those who would be eligible for the treatment but also concurrently begin to suffer from the above ailments. For this reason, the possible benefits of Growth Hormone Replacement Therapy in those patients who are suffering from critical, acute injuries must be weighed against the possible risks of hormone treatment. The pros and cons of hormone replacement therapy must be properly evaluated.

Precautions: Is it time to think about stopping hormone replacement therapy?

General

Therapy with Lyophilized Genotropin Powder, should be guided by HRT doctors who have experience in the management and diagnosis of patients with Growth Hormone Disorder, as should be the case with the usage of any Growth Hormone preparation.

Caregivers and patients that will inject Genotropin in situations that are medically unsupervised are sternly advised to attain proper instruction and training about how to properly use Genotropin. This training should be given by a specialized doctor or other properly trained health professional.

Patients who suffer from Growth Hormone Disorder in addition to an intracranial lesion need to visit their doctor with regularity to monitor the development or recurrence of the underlying process of their disease. A survey of reports regarding the use of somatotropin replacement therapy shows no correlation between somatropin replacement therapy and tumors of the central nervous system. Later in life, there has been insufficient research to discover is there is any sort of causal relationship between the occurrence of Central Nervous System tumors and Somatropin Treatment

It is also vitally important that patients be carefully monitored for the formation of malignant lesions on the skin.

Caution is advised if Human Growth Hormone Therapy is administered to those that are already suffering from diabetes mellitus, because the level of insulin intake may need to be changed as a result of the hormone therapy. Those undergoing Growth Hormone Replacement Therapy should be monitored for the development of a glucose intolerance because Growth Hormone can sometimes give rise to a state where one is more resistant to insulin. Those patients that have a glucose intolerance or diabetes must be closely monitored while taking Genotropin. If major complications begin to arise it may be time to think about stopping hormone replacement therapy.

With those that have been diagnosed with hypopituitarism (a disease that is the result of multiple deficiencies of the hormonal system), the normal regimen of Hormone Replacement Therapy should be closely monitored when Genotropin treatment commences. Hypothyroidism can develop as one is treated with Genotropin, and as a result, inadequate medical response to hypothyroidism can cause Genotropin to become less effective or ineffective. For this reason, it is pertinent that patients get tested for proper thyroid function periodically, and if the thyroid becomes less active, thyroid hormone should also be administered in tandem with Genotropin.

Pediatric patients who have disorder of the endocrine system such as Growth Hormone Disorder have been shown to have a greater risk of developing a slipped capital femoral epiphyses. Any young patient that develops a limp or begins to complain of knee or hip pain as they undergo Growth Hormone Therapy needs to undergo evaluation.

Intracranial hypertension (IH) with nausea, vomiting, headache, visual disruption, and/or papilledema has been shown to be a side effect in a small minority of patients that take Growth Hormone therapies. These issues occur usually within the first two months after one begins GHT. In each reported case, and signs of Intracranial Hypertension are alleviated after hormone therapy is terminated or the dosage is adjusted to a more minute amount. Examination of the ocular fundus is recommended as a patient begins therapy, and it is also advised that they are examined for Intracranial Hypertension periodically as he or she continues Therapy.

Before undergoing adult treatment for Growth Hormone Deficiency, a patient who has undergone puberty and received GHRT in their childhood needs to be reevaluated in a manner that is recommended in the section Indications and Usage. If it is advisable to continue treatment, Genotropin therapy should continue at a lower level of dosage that is more appropriate for adults who have Growth Hormone Disorder.

Drug Interactions

Undergoing treatment with glucocorticoids concomitantly with Growth Hormone can cancel out the growth promotional effect of Hormone Therapy. Pediatric Growth Hormone deficiency patients that have a coexisting deficiency of ACTH aneed to have their dose adjusted carefully so that the glucocorticoid does not inhibit the effect of the Growth Hormone Replacement Therapy. For more information, see Precautions. Though there is limited published research on the subject, it has been indicated that in humans, GHT increases antipyrine evacuation mediated by CP450 (cytochrome P450). The available data seems to suggest that Growth Hormone administration can alter the evacuation of the compounds that become metabolized through the liver enzyme CP450. These compounds include sexual steroids, cyclosporine, anticonvulsants, and corticosteroids. It is advised that a patient undergo careful monitoring when Genotropin is injected in addition to other drugs that are metabolized by the liver enzyme CP450.

Mutagenesis, Carcinogenesis, and Fertility Issues with Human Growth Hormone Replacement Therapy

Studies of carcinogenicity have yet to be conducted in regard to bio identical Human Growth Hormone. A number of tests have shown no evidence of the mutagenicity of Human Growth Hormone. The tests conducted include the Ames Test in which gene mutations are introduced to bacteria, mutation of genes in mammalian cellular cultures grown in vitro (L5178Y cells), and damage to the chromosomes of intact animals (rat marrow cells). To learn more about issues regarding fertility, go to the section entitled Pregnancy.

Pregnancy Category B

Fertility studies enacted in regard to Genotropin at dosage levels of 0.3, 1, and 3.3 milligrams per kilogram per day delivered subcutaneously to rats and dosage levels of 0.08, 0.3, and 1.3 milligrams per kilogram per day delivered intramuscularly to rabbits resulted in a reduction in the body weight of the mother but the reduction was not teratogenic. The highest administered doses were about 24x and 19x the normal human levels for therapy, respectively, based upo the surface area of the body.

Rats received subcutaneous doses of Genotropin during gametogenesis and through the initial seven days of pregnancy at a rate of 3.3 mg/kg/day. This level is about 24x higher than the normal human dosage. This dosage produced extended cycles of estrous in females (known as anestrus), and fewer, less motile sperm in male rats. When Genotropin was administered to female, pregnant rats during days one through seven of gestation at 3.3 mg/kg/day, a modest increase of fetal mortality occurred. When administered 1 mg/kg/day (which is around 7x the normal human dose) rats displayed estrus cycles which were only slightly extended. At a dosage of 0.3 mg/kg/day there were no noted effects.

In postnatal and perinatal study of rats, doses of Genotropin at 0.3, 1, and 3.3 mg/kg/day resulted in the promotion of growth of the dams but not of the fetuses, themselves. Young rats exposed to 3.3 mg/kg/day were discovered to have an increase in weight gain during the suckling period, but these effects were no longer apparent at ten weeks old. There were no negative effects observed during morphogenesis, gestation, lactation, parturition, postnatal continued development, or the fertility of the offspring as a result of Genotropin. It is important to note, however, that there have been no adequate, well-conducted studies of pregnant women in regard to Genotropin. Studies regarding animal reproduction do not always correctly predict the equivalent human response to the same stimulus, therefore, Genotropin should only be used during pregnancy if it is clearly and absolutely needed.

Mothers who are nursing

No studies have been conducted with regard to Genotropin and nursing mothers. At this point it is not clear whether the drug is present in human milk. Since it is a fact that a number of drugs are released in human milk, caution must be exercised with the administration of Genotropin to a nursing female.

Bioidentical hormone replacement therapy side effects

As with all drugs that are protein-derived, a small minority of patients can begin to manufacture antibodies to the administered protein. Growth Hormone antibody with a lower binding than 2 mg/L has not been shown to be associated with the attenuation of growth. In those cases where the capacity for binding is greater than 2 mg/L, antibodies sometimes interfere with the desired results for growth.

In a survey of 419 pediatric GHT patients which were administered Lyophilized Genotropin powder, 244 were previously treated with Genotropin and 175 were undergoing GHT for the first time. Baseline presence of Anti-Growth Hormone antibodies had developed in 6 patients who were previously treated with Genotropin. 3 of those 6 once again tested negative for anti-Growth Hormone antibodies during six to twelve months of Genotropin treatment. Out of the rest of the group (413 patients), 8 (1.9% of the population) acquired detectable levels anti-Growth Hormone antibodies during Genotropin treatment. None of these antibodies reached a binding capacity of greater than 2mg/L. As a result, the patients who tested positive for Human Growth Hormone antibodies experienced no hindrance to Genotropin's intended growth response.

Genotropin preparations do contain trace amounts of periplasmic E. coli peptides (abbreviated PECP). Antibodies resistant to PECP develop in a small minority of those treated with Genotropin, but these antibodies do not create any issues of significance.

Clinical Genotropin studies with pediatric Growth Hormone Deficient patients uncommonly reported the following side effects: burning and pain around the administration site, nodules, inflammation, fibrosis, rash, bleeding, or skin pigmentation. Other side effects include headache, hypothyroidism, lipoatrophy, hematuria, and mild hyperglycemia.

There have been a limited number of reports of leukemia among young patients who have undergone GHT including pituitary-derived Growth hormone and Bio-Synthetic somatropin. The correlation, if any, between GHT and leukemia is unclear at this time.

In a survey of clinical Genotropin trials in 1,145 adults with Growth Hormone Deficiency, the most reported side-effect was mild or moderate fluid retention resulting in hypoesthesia, paresthesia, myalgia, peripheral edema, stiffness and pain in the extremities, peripheral swelling, and arthralgia. The previous side effects were noted early in Genotropin Therapy and they often subsided with time or disappeared with a reduction in dosage.

Table 2 shows side effects reported by five percent or more of adult patients with Growth Hormone Deficiency in a variety of clinical trial settings and after a number of different Genotropin treatment durations. Also corresponding rates of side effect incidence are listed for those who underwent placebo treatment during the six-month portion of double-blind clinical trials.

Table 2

Side effects reported by greater than or equal to 5 percent of a total of 1,145 Growth Hormone Deficient adult patients who participated in clinical administration of placebo and Genotropin, arranged by treatment duration, double-blind, and open-label phase. Percentages are rounded to the nearest 0.5%

Genotropin

Side-effects

Placebo Patients

0-6 months

n = 572

# Genotropin Patients

0-6 months

number of participants = 573

Percentage patients six-twelve months

n = 63

Percentage of patients twelve-eighteen months

n = 63

Percentage of patients eighteen-twenty four months

n = 60

Percentage Patients Reporting Side Effect

Peripheral Swelling 5.0 / 17.5* / 5.5 / 0 / 1.5

Infection of the upper respiratory tract 14.5 / 15.5 / 13.0 / 15.0 / 13.5

Arthralgia 4.0 / 17.0* / 7.0 / 6.5 / 3.5

Extremity stiffness 6.0 / 15.0* / 6.5 / 1.5 / 3.5

Tingling sensation 1.0 / 9.5* / 2.0 / 3.0 / 0

Peripheral edema 2.5 / 11.0* / 3.0 / 0 / 0

Extremity Stiffness 1.5 / 8.0* / 2.5 / 1.5 / 0

Headache 8.0 / 10.0 / 6.0 / 0 0

Pain reported in back 4.5 / 3.0 / 3.5 / 5.0 / 5.0

Muscle pain 1.5 / 5.0 * / 2.0 / 5.0 / 7.0

Fatigue 4.0 / 6.0 / 4.5 / 6.5 / 1.5

* Significant increase in comparison to those taking placebo. P n =

# of patients that received treatment in the specific period.

% = Patient percentage who experienced the side effect in the specific period.

In expanded study which occurred post-trial, diabetes was reported in twelve out of a total 3,031 patients as they were treated with Genotropin, only 0.4$ of the population. Each of the twelve patients showed risk factors for diabetes such as significant obesity or high levels of glycated hemoglocin, before beginning Genotropin Treatment. Out of that same pool of 3,031 Genotropin-receiving patients, only 2% (61) developed carpal tunnel symptoms, and this number dropped by 52 after treatment interruption or dosage adjustment, and the other nine found their symptoms alleviated by surgery. Other side effects that were reported in the study included hypoesthesia and general edema.

Overdose

Little information is available regarding chronic or acute overdosage of Lyophilized Genotropin Powder. Growth Hormone adminstered intravenously has shown evidence that it results in a severe decrease in the plasma of the blood. For this reason, hyperglycemia sometime occurs as a result. It is hypothesized that this same issue could occur in the rare instance where a very high dose of Genotropin is administered subcutaneously. Overdosage over the long term could result in hormone imbalance symptoms and signs of acromegaly that are consistent with the nature overproduction of Human Growth Hormone. Make sure to engage in safe hormone replacement therapy.

Administration and Dosage

The appropriate dosage of Lyophilized Genotropin Powder is dependent upon the individual needs of the patient. The dosage for the week ideally is divided into six or seven SC injections. The injection of Genotropin can be administered to the abdomen, buttocks, or thigh. The area where the subcutaneous injection occurs should change each day so that lipoatrophy is averted.

For Pediatric Growth Hormone Deficiency patients, a dosage of 0.16 to 0.24 milligrams per kilogram of body weight per week is generally the recommended dosage.

For Adult Growth Hormone Deficiency Patients, the initial recommended dose when one begins therapy is generally not greater than 0.04 mg/kg/week. Every four to eight weeks, the dosage can be increased as needed for the patient up to a max of 0.08 mg/kg/week dependent upon the patient's tolerance for the treatment. Response to the medicine, developed side effects, and levels of age-adjusted Insulin-Like Growth Factor-1 in serum can all be used to provide a guide leading to a proper titration of dosage. This regimen tends to lead to larger weight-adjusted treatment for woman than men, and smaller weight-adjusted treatment for obese and older patients.

Do not inject Genotropin intravenously.

Genotropin is provided in a two-chambered cartridge, with the lyophilized powder located in the front compartment and a dilutant located in the rear compartment. A reconstitution device mixes the dilutant and the powder.

Each device has its own directions to follow for proper reconstitution. It is vital that the medicine is not shaken, because shaking can lead to denaturation of the primary ingredient.

Before injection, all parenteral medicinal products need to be visually inspected for discoloration and particulate matter, if the container and solution permit. If the solution has become cloudy, it is vital that the contents are not injected.

Caregivers and patients that will administer the Genotropin in situations in situations where they are not medically supervised are urged to visit one of many bioidentical hormone physicians other appropriately qualified health professionals in order to acquire the appropriate instruction and training regarding the proper administration of Genotropin.

Storage and Stability

Except in proceeding situation, store Lyophilized Genotropin Powder in refrigeration at 2-8 degrees Celsius (36-46 degrees Fahrenheit). Refrain from freezing. Store in a light-protected area.

The 1.5 mg Genotropin Cartridge contains a dilutent without a preservative. After the drug is reconstituted, a cartridge can be stored safely for up to a day. Use it only once and throw away any solution that remains.

The 13.8 and 5.8 mg Genotropin cartridges contain a dilutent that is laced with a preservative. For this reason, these cartridges may be stored in refrigeration as long as three weeks.

The Genotropin Miniquick Growth Hormone Delivery Device needs to be refrigerated before it is dispensed, but it can be placed in storage at a temperature of 25 degrees Celsius (77 degrees Fahrenheit) or less for a period of as long as 3 months after it is dispensed. The dilutent does not contain preservative. After the Genotropin Miniquick has been reconstituted, it may be placed in storage under refrigeration for up to one day before usage. After it is used one time it should be discarded.

How Supplied

Lyophilized Genotropin Powder is available for purchase in the following configurations:

1.5 milligram two-chambered cartridge (without preservative)

Preconfigured in a Genotropin Intramix GH Reconstitution Device which is packaged with a single pressure release needle

Five Cartridge Package National Drug Code 0013-2606-94

5.8 milligram two-chambered container (added preservative)

5 mg/mL concentration (about 15 IU/mL)

Intended for usage with the Genotropin Mixer GH Reconstitution device and/or the Genotropin Pen 5 GH Delivery Device

Five Cartridge package National Drug Code 0013-2626-94

One Cartridge package National Drug Code 0013-2626-81

Preconfigured in a Genotropin Intramix GH Device for Reconstitution and packaged with one needle which functions through pressure release.

Package of five National Drug Code 0013-2616-94

Package of one National Drug Code 0013-2616-81

13.8 milligram two-chambered container (added preservative)

12 mg./mL concentration (about 36 IU/mL)

Intended for usage with the Genetropin Mixer GH Reconstitution device and/or the Genotropin Pen 12 GH Delivery Device

Box of Five National Drug Code 0013-2646-94

Box of One National Drug Code 0013-2646-81

Genotropin Miniquick GH Delivery Device contains a two-compartment cartridge containing a two-chamber cartridge of GENOTROPIN (no preservative)

After it is reconstituted, every Genotropin Miniquick released a 0.25 mL fixed dose without regard to strength. It is available in the proceeding strengths in packages of seven.

0.2 milligram National Drug Code 0013-2649-02

0.4 milligram National Drug Code 0013-2650-02

0.6 milligram National Drug Code 0013-2651-02

0.8 milligram National Drug Code 0013-2652-02

1.0 milligram National Drug Code 0013-2653-02

1.2 milligram National Drug Code 0013-2654-02

1.4 milligram National Drug Code 0013-2655-02

1.6 milligram National Drug Code 0013-2656-02

1.8 milligram National Drug Code 0013-2657-02

2.0 milligram National Drug Code 0013-2658-02

The Importance of B12 for Energy and Health

Vitamin B12 is one of many important and vital nutrients used by the body to foster optimal health. Vitamin B12 is a vitamin which encourages peak function of blood cells while also maintaining the health of the nerves.

The vitamin also has another function central to human life: it is one of the necessary materials for the construction of DNA molecules, which store all of the data which contribute to human development. This nutrient also helps keep the body energized and strong, and Vitamin B12 Deficiency can lead to a condition known as Megaloblastic Anemia.

How Does the Body Absorb B12?

Vitamin B12 is drawn directly from the food that we eat. It is absorbed through a relatively simple process. The first step takes place within the stomach. The stomach contains powerful hydrochloric acid which has the ability to break down the foods we eat and render them into simpler parts.

When consumed as part of a meal, Vitamin B12 is connected to proteins in the food that we eat, and hydrochloric acid breaks the bonds which connect Vitamin B12 to the protein. After the Vitamin B12 Molecule has been freed, it then reacts with another molecule known as Intrinsic Factor.

Intrinsic Factor is a protein which bonds with B12, allowing the nutrient to be taken in by the body. There are some people that actually lack the ability to make Intrinsic Factor, which causes them to absorb very low levels of B12. This condition is known as Pernicious Anemia.

How Much B12 Does the Body Need?

The human body requires Vitamin B12 at all stages of life, but the requirements vary dependent upon age. Children need an amount which slowly grows from 0.4 micrograms in the first six months of life, to 1.8 micrograms per day at 13 years. From 14 years old through adulthood, the body has a relatively steady requirement for B12 which is around 2.4 micrograms.

Women that are pregnant need a little more in order to promote healthy fetal development, around 2.6 micrograms. Women that are breastfeeding need the highest levels, around 2.8 micrograms. This makes sense, because early in life, the child is completely dependent upon breast milk for nutrition, so the mother must increase her own production to compensate.

What Are the best Sources of Vitamin B12?

Vitamin B12 is one of a number of nutrients that are only available to human beings through either animal or synthetic sources. Below are a number of sources of Vitamin B12:

• Milk Products

• Eggs

• Poultry

• Meat

• Fish

• Some Yeast Products

• Supplements

• Fortified Cereals

• Other Fortified Foods

• Clams

• Liver

The final two suggestions, Liver and Clams, contain the most significant levels of B12. B12 is processed by the liver in animals that cannot produce it naturally, and it is synthesized in herbivores that do have the capability to make their own Vitamin B12 from plant material. As a result, aside from clams, liver is the single best source for Vitamin B12.

What is Vitamin B12 Deficiency?

A deficiency of Vitamin B12 brings about a rather particular set of symptoms, among which are:

Physical Symptoms of B12 Deficiency

• Weight Loss

• Appetite Suppression

• Constipation

• Weakness

• Fatigue

• Megaloblastic Anemia

Neurological Symptoms of B12 Deficiency

• Tingling and Numbness in the Feet and Hands

• Soreness of the Tongue or Mouth

• Cognitive Decline

• Dementia

• Confusion

• Depression

• Balance Issues

It should be noted right away that a deficiency in Vitamin B12 can cause neurological symptoms, even if the physical symptoms do not manifest themselves. Some of the neurological damage resulting from B12 Deficiency is also irreversible, so it is incredibly important to diagnose and treat Vitamin B12 Deficiency as soon as possible.

Although the overall need for B12 is lower for children than adults, severe issues can occur as a result of prolonged Vitamin B12 Deficiency early in life. B12 Deficiency can cause many problems for infant patients.

The Symptoms of Childhood B12 Deficiency include:

• Megaloblastic Anemia

• Slow Development

• Disorders of Movement

• General Failure to Thrive

If you notice any of these symptoms, it is important to make an appointment with a pediatrician as soon as possible. The symptoms of Vitamin B12 Deficiency share similarities to other developmental disorders, and it is important to get an appropriate diagnosis as soon as possible.

How is Vitamin B12 Deficiency Cured?

Generally, the way to resolve B12 Deficiency is through direct intervention with Injections of Vitamin B12. B12 Injections allow for maximum absorption, because B12 is delivered directly to the body, bypassing more limited digestive absorption. If an immediate injection is not deemed necessary, a physician may recommend taking Vitamin B12 Orally in high doses in order to resolve the Deficiency.

One study compared the effectiveness of Oral B12 versus B12 Injections. Researchers found that oral Vitamin B12 was able to replicate the effectiveness of injections over time. The optimal way to restore B12 through oral supplementation was to take high doses of B12 (2000 micrograms) every day initially, then cutting the dose in half. After cutting down to half doses, it was eventually possible to cut down to weekly, and finally monthly, doses, before simply allowing the patient to proactively make steps to maintain healthy levels of Vitamin B12.

Although both forms of supplementation are effective, the ability of the patient to absorb the nutrient through the digestive tract, and the severity of the deficiency will be the most significant factors which lead the physician to take the appropriate course of action.

How are B12 Shots Injected?

Like Testosterone Injections, B12 Injections are Delivered Intramuscularly.

How are Vitamin B12 and Folic Acid Connected?

Individuals that consume a high level of Folic Acid in their diet can make the dangerous symptoms of severe Vitamin B12 Deficiency less apparent. Folic acid has the ability to resolve Megaoloblastic Anemia without resolving the underlying neurological complications of the condition.

There are even studies which provide evidence that high levels of folate in the blood stream can eventually make anemia worse and amplify the neurological issues related to B12 Deficiency, increasing the risk of cognitive decline.

This combination of Folic Acid Overload and B12 Deficiency can lead to permanent nerve damage. Because of this significant risk, healthy men and women should take no more than 1,000 micrograms of Folic Acid per day.

Who is at Greatest Risk of B12 Deficiency?

There are a number of issues which can lead directly to Vitamin B12 Deficiency. These causes include:

• Pernicious Anemia

• Lack of B12 in the diet

• Inability to appropriately absorb B12

• Post-surgical inability to properly absorb Vitamin B12

Although these are the four leading causes of Vitamin B12 Deficiency, there are many cases in which the cause of B12 Deficiency is unclear.

Who is Most at Risk of B12 Deficiency?

Aging Adults

As men and women grow older, the odds of developing Vitamin B12 Deficiency grow. There is a condition known as Atrophic Gastritis, which causes the stomach to produce abnormally low levels of Hydrochloric Acid. As a direct result of this, B12 Absorption drops.

This condition affects ten to thirty percent of older men and women. This change in hydrochloric acid production can also change the composition of gut flora, leading to the formation of bacteria which consume Vitamin B12 to propagate, reducing the amount available to the body itself.

Because this disorder reduces the body's ability to break down food sources of Vitamin B12, it can be easily treated through direct supplementation. In addition to this, foods fortified with B12 are also a useful source, because the synthetic form of B12 present in most fortified foods is easier to absorb than natural B12 for these individuals.

Because of the risk of Atrophic Gastritis, physicians recommend getting B12 from either fortified foods or supplements after the age of fifty. It should also be noted that elderly men and women that have this disorder should intake more Vitamin B12 than Recommended Daily Values Suggest.

People with Pernicious Anemia

Pernicious Anemia is a medical issue which afflicts between one and two percent of adults over fifty. The main issue with regard to these patients is they either produce no or little Intrinsic Factor, which is necessary in order for the digestive system to properly absorb B12.

The most effective way to treat this medical condition is through the use of Vitamin B12 Injections. Injections bypass the need for Intrinsic Factor and supply usable Vitamin B12 directly to the body. It may also be possible for some patients to use high doses of oral B12 in lieu of Vitamin B12, because around one percent of orally ingested Vitamin B12 can be absorbed even without the agency of Intrinsic Factor.

People with General Gastrointestinal Problems

There are certain diseases of the small intestine and stomach which complicate Vitamin B12 Absorption, including Crohn's Disease and Celiac Disease. These complications can prevent patients from getting the Vitamin B12 that they need from a normal diet.

Because of this inherent deficiency, some individuals with diseases such as these can experience very subtly decreased cognitive ability as a direct result of childhood Vitamin B12 Deficiency. In addition to this, they can also eventually suffer from dementia or Megaloblastic Anemia. For this reason, it is undeniably important for anyone with gastrointestinal disorders to evaluate their B12 Levels on a regular basis as a preventative measure against these conditions.

People that Have Undergone Surgery of the Stomach or Small Intestine

Certain surgeries can impact the digestive system's ability to absorb healthy levels of Vitamin B12. Individuals that undergo gastric bypass surgery or other weight loss surgeries often find that their ability to absorb Vitamin B12 Decreases as a result of less Intrinsic Factor and Hydrochloric Acid release by the stomach.

Any surgery which removes part or all of the stomach also leads to this issue. This has particular effect upon the body's ability to absorb natural forms of B12. Removal of the end of the small intestine, known as the distal ileum, can also inhibit or stop B12 Absorption. Anyone that goes under the knife for gastrointestinal surgery of any kind should be regularly monitored for any nutritional complications.

Vegetarians

Vegans and vegetarians are at a high risk of developing B12 Deficiency if they are not conscientious about their diet. The only natural sources of B12 for human beings are derived from animal products, and, unless vegetarians look to supplemental sources of B12, it will be impossible to get the necessary Vitamin B12 for optimal health.

Vegetarians that still use milk products or eat eggs do not have this same levels of risk, and pescatarians can easily get the B12 they need from fish sources. Luckily for vegetarians, there are now a number of fortified sources of B12, the most common of which is contained within many breakfast cereals.

Lactating and Pregnant Vegetarians, as well as their Infants

During pregnancy, the fetus receives necessary Vitamin B12 through the placenta. After being born, B12 is received through the breast milk. If infants are breastfed by vegetarian mothers, they often receive abnormally low levels of B12, which can hinder their optimal development. If B12 Deficiency is not caught very early, it can cause very serious and potentially life-long problems.

American Dieticians very strongly suggest that both lacto-ovo vegetarians and vegans take ample supplemental B12 during pregnancy in order to ensure the health of the infant. They should also ask their doctors about providing their young children with B12 Supplements to eliminate all potential risk.

Connections Between Vitamin B12 Deficiency and Negative Cardiovascular Outcomes

Among first world countries, heart disease is usually the number one cause of death. In developing countries, the threat of Heart Disease continues to increase as other easily preventable causes of death are eliminated, and changes in diet and lifestyle promote increased odds of the condition. Some major risk factors of Heart Disease are:

• Diabetes

• Obesity

• Low HDL Cholesterol

• High LDL Cholesterol

• Hypertension

• High Homocysteine Levels

Vitamin B12 and Homocysteine

Homocysteine levels are strongly associated with Vitamin B12 Consumption. Homocysteine is an amino acid compound that is necessary for a healthy cardiovascular system, the problem is that a lot of individuals produce way too much of it.

Excessively high Homocysteine production causes a number of issues which reduce the function of the heart and increase the risk of heart complications. It encourages the formulation of clots, prevents proper vasodilation, and changes the muscular composition of veins and arteries. It also causes the breakdown of fat in the blood stream, releasing dangerous free radicals into the body.

Vitamin B6, Folate, and Vitamin B12 are vitally important in the metabolism of Homocysteine. In the result of B12 Deficiency, Homocysteine production can rise in a dangerous manner. Vitamin B12 Supplementation in combination with Folate Supplementation has been shown to have an ameliorative effect on Homocysteine Production, encouraging a reduced risk of stroke.

To this point, the evidence is incomplete in regard to whether providing B12 Supplementation improves other aspects of Cardiovascular Health in at-risk patients. This does not, however, diminish the importance of maintaining healthy B12 consumption throughout the lifespan, because, although Vitamin B12 may be limited in its ability to treat heart problems, proper use of B12 throughout the lifespan can help reduce the risk of developing these complications in the first place.

Vitamin B12 and the Brain

B12 May Protect the Brains of the Elderly

In a recent study conducted by scientists at Oxford, a strong correlation was found between the overall volume of the brain, and healthy Vitamin B12 consumption. In this study, researchers collected data from 107 participants. These participants ranged in age from sixty one to eighty seven. None of the subjects displayed any signs of cognitive decline or issues with memory. The median age of the subjects was seventy three, and 46% of the participants were men.

The scientists then proceeded to draw blood in order to assess the Vitamin B12 levels of each patient. Vitamin B12 is found in highest concentrations in milk, fish, and meat. In addition to blood testing, each subject also underwent annual MRI brain scans in order to visually assess the condition of the brain. They also received a yearly physical and memory evaluation.

Among the 107 men and women, none of them were found to have a Vitamin B12 Deficiency. Researchers took the data that they compiled from this study and compared it to studies of patients which suffered from Vitamin B12 Deficiency. They discovered that men and women with Vitamin B12 Deficiency were six times more likely to have smaller brain volumes than patients that had healthy levels of B12.

Although they were able to establish this link, the scientists were not able to provide evidence regarding the impact of brain size on cognitive impairment.

Maintaining Healthy Vitamin B12 Levels Helps Prevent Cognitive Issues Later in Life

The project leader, Anna Vogiatzoglou, explains that there are a lot of different factors which contribute to adverse changes in the condition of the brain, but her study shows that there is a powerful connection between Vitamin B12 and the preserving the size of our brains.

Although her study did not have the ability to establish psychological and cognitive changes related to changes in brain size with age, she hypothesizes that making sure that we get enough Vitamin B12 throughout our lives is a thoughtful and productive step in preserving proper and healthy brain function later in life. By taking this healthy and conscientious step, there is a significant chance that we can preserve our memory more effectively with age.

Although the study provides a positive link in regard to Vitamin B12 Levels and Brain Shrinkage, the study did not analyze the effect of Vitamin B12 Supplementation as a preventative treatment for elderly patients.

It appears that, like the connection between Cardiovascular Health and Vitamin B12, there is a limited ability for Vitamin B12 to be a treatment for conditions related to untreated Vitamin B12 Deficiency, but maintaining healthy Vitamin B12 Levels throughout the lifespan can help prevent significant issues later in life.

Does Excessive B12 Supplementation Lead to any Health Risks?

Vitamin B12 has an extremely low capacity for toxicity. Because of this, there is little to no risk of complications resulting from the over-consumption of the nutrient. Vitamin B12 is water-soluble, and nutrients of this type are generally absorbed by the body as needed, then released into the urine. Fat soluble Vitamins generally carry a certain risk of overdose (Vitamin A being one particular example).

Vitamin B12 Final Thoughts

As you can see, it is vitally important to make sure that your body gets a healthy dose of Vitamin B12. If you are conscientious, this is one of the best ways to preserve your cognitive health deep into old age.

There is really no reason to experience Vitamin B12 Deficiency, unless your body is beginning to have trouble processing the nutrient. If you have a feeling you aren't getting enough Vitamin B12 in your diet, we actively encourage you to seek out a supplement. There is absolutely no downside, and it can have a tremendously positive impact upon your cardiovascular system, neurological system and general energy levels.

Endocrine Disrupting Chemicals in Pesticides and Plastics

Over the last ten years, clinical and ecological research continues to suggest that many chemicals, both synthetic and natural, have the ability to disrupt the hormone balance of the endocrine system, producing various negative effects in all sorts of creatures, including birds, fish, wildlife, and even human beings.

When discussing the hormonal implication of these chemicals, scientists and researchers have labeled these chemicals endocrine disruptors. In today's 21st century world, these products are everywhere in our lives. Some of the most common places where these chemicals exist are pesticides, cosmetics, toys, foods, flame retardants, detergents, metal food cans, and some plastic bottles.

Today, there is a limited body of scientific data available regarding these chemicals, but there is a legitimate concern over how these chemicals may have an impact on human health. In the environment, there are areas which are polluted with endocrine disrupting chemicals to an extent that ecological populations are experiencing deleterious effects directly as a result. These negative health impacts have also been proven in a laboratory atmosphere.

Although it is clear that Endocrine Disrupting Chemicals are a health risk under certain circumstances and concentrations, it can be hard to study the health impact of these chemicals, because people are generally exposed to a number of these chemicals at varying concentrations at the same time. There are government and non-profit organizations dedicated to clarifying the health risks and implications associated with Endocrine Disruptors, two of which are the National Toxicology Program and the National Institute of Environmental Health Science.

These groups support and fund scientific studies aimed at fostering a more complete understanding regarding how these chemicals impact hormone balance in an effort to protect both human beings and wildlife from the negative impact of Endocrine Disrupting Chemicals. In the near and distant future, these programs hope to minimize the domestic and global environmental and health impact of these chemicals and to discover ways to mitigate the negative effects.

What is an Endocrine Disrupting Chemical?

Endocrine Disrupting Chemicals are synthetic or naturally occurring chemicals which have the capacity to interfere with the secretion or functional capacity of hormones produced by the endocrine system. These chemicals have the ability to significantly alter hormone balance in both humans and animals, leading directly to negative health consequences. A number of these Endocrine Disruptors have been strongly correlated with immune, neural, reproductive, and developmental issues in both captive and wild animal populations.

Many researchers also believe that these chemicals and compounds also have the ability to negatively impact human health at existing concentrations. There is some correlation between reduced fertility and Endocrine Disrupting Chemicals. These chemicals also appear to increase the risks of certain health conditions, including several cancers.

In addition to Endocrine Disruptors and Endocrine Disrupting Chemicals, these chemicals are also referred to by a number of other names, including Endocrine Active Compounds, Environmental Hormones, and Endocrine Modulators.

There are forms of chemical pollution that affect various types of hormone balance, but the group of chemicals that have received the largest body of scientific study are those that increase the physiological influence of Estrogen. A number of other chemical disruptors have been identified however, including those that encourage the production of thyroid hormones, androgens, and progesterone, and those that inhibit the production of Estrogens and Androgens.

What is the Importance of the Endocrine System?

Along with the Neurological System, the Endocrine system is the primary way that the body communicates changes from disparate areas of the body. The Endocrine System also plays a central role in the coordination and control of numerous physiological functions. The Endocrine System produces these changes directly through the secretion of hormones from Endocrine Tissues situated throughout the body, including the pancreas, thyroid, pituitary, testes, and ovaries. These hormones then enter the blood stream where they flow to target organs and affect change.

Hormones are able to conduct the complex orchestra of necessary functions which keep us happy and healthy. One example of how hormones function is the complex way that the reproductive system, nervous system, fat, liver, gut, and kidneys work together in order to control and maintain various metabolic functions, including:

• Reproduction

• Development and Growth

• Energy Level of the Body

• Hormone Homeostasis

• Response to Injury, Stress, and Outside Influences

Endocrine Disrupting Chemicals interfere with the normally-closed set of signals flowing throughout the body to keep us healthy, leading directly to hormone imbalance which causes a variety of negative consequences.

How do Endocrine Disrupting Chemicals Work?

Animal research has provided us with a lot of insight regarding the impact of Endocrine Disrupting Chemicals. There are a number of different mechanisms through which EDCs have the ability to alter the normal function of the human body.

Endocrine Disruptors have the ability to:

• Substitute partially or completely for hormones produced naturally by the human body, such as Thyroids Hormones, Androgens, and Estrogens. These chemicals imbalance the system by overstimulating the body with the effects of a particular hormone.

• Block the normal and healthy function of a hormone by blocking cell receptors and preventing hormones from making their connections. In these cases, the target organ does not receive the full physiological signal, and the body displays symptoms and signs of deficiency. Chemicals that produce these effects are categorized under terms such as Anti-Androgens and Anti-Estrogens.

• Other Endocrine Disruptors actually have the ability to block or alter the way that hormones and hormone receptors are controlled or created. One example is that there are certain EDCs which can prevent the proper metabolism of hormones by the liver.

What are Some Particular Examples of Endocrine Disrupting Chemicals?

There are a large number of chemicals which have the capacity to alter normal Endocrine Function in a variety of ways. A few well known Endocrine Disrupting chemicals are, PCBs, Dioxin, and the medication Diethylstibesterol (also known as DES), and pesticides like DDT .

There are other chemicals, commonly plasticizers and pesticides, which have been shown to have Endocrine Disrupting effects in animal studies, such as Bisphenol A (also known as BPA). Bisphenol A is a synthetic chemical that is in many plastic products such as bottles, which leach from certain products when exposed to heat. BPA has many industrial applications, including the creation of beverage and food containers, and well as an ingredient of resins used in dental sealants.

Another large group of Endocrine Disrupting Chemicals are known as phthalates. The industrial application of these synthetic chemicals is to improve the flexibility or soften plastics made from polyvinyl chloride. One common phthalate is DEHP. This chemical is used in the production of a large number of polyvinyl products such as food packages, clothes, car products, building materials, children's products, and medical tools. Scientists with the National Toxicology Program have found that there may be a link between DEHP and developmental issues in young children, especially male infants which are seriously ill.

Some of the most common forms of naturally occurring Endocrine Disrupting Chemicals are known as Phytoestrogens. These chemicals are naturally produced in some plants, and have the ability to partially mimic the effects of Estrogen under some circumstances. Some of these chemicals can be found in foods and other products produced from soy, such as daidzein and genestein.

Representatives of the National Toxicology Program recognized the importance of evaluating the risks of Endocrine Disrupting Chemicals upon human reproduction, and created The Center for the Evaluation of Risks to Human Reproduction. This group analyzes various products for signs that they may impact normal fetal and childhood development. The Center has determined that seven Phthalate compounds have Endocrine-Disrupting Effects, as well as one particular Phytoestrogen known as Genistein. Genistein is an ingredient in infant formulas derived from soy.

How do People become Exposed to Endocrine Disrupting Chemicals?

There are a number of ways that individuals of all ages can become exposed to EDCs. It can enter through their dietary choices, the medicines they are prescribed, and even the make-up they put on their face. Exposure can occur directly through the skin, through the digestive system, and through breathing.

Many chemicals which have these Endocrine Disrupting qualities take a long time to degrade or otherwise dissipate, such as the pesticide DDT. For this reason, many EDC Chemicals can be a health risk for long after they are initially used.

What is the Current State of Endocrine Disrupting Chemical Research?

The National Institute of Environmental Health Science has spent over thirty years researching the impact of medical Diethylstilbestrol on human patients. This chemical was used from the 1940s to the 1970s because medical professionals mistakenly believed that the chemical had the ability to reduce the risk of miscarriage for patients at serious risk.

In 1972, it was discovered that daughters born to mothers that were treated with DES had a significantly increased risk of experiencing a very uncommon form of vaginal cancer. In addition to this, DES produced many other changes in children of both sexes born to mothers that took the drug. The National Institute of Environmental Health Science performed extensive animal studies which proved the link between exposure to DES and the development of birth defects and increased cancer risk.

Leading directly from this initial, stunning series of discoveries, scientists with the NIEHS have continued to study other chemicals which interact adversely with estrogen receptors. Scientists continue to broaden the body of knowledge regarding Endocrine Disrupting Chemicals in a number of different ways, including:

• Creating new tools and models to reveal new information about how Endocrine Disruptors function

• Uncovering new techniques to discover which chemicals produce Endocrine Disrupting Effects

• Studying the impact of EDC exposure throughout the lifespan, and how it impacts health

• Studying the effects of EDCs in existing human patient populations

• Creating new tests and biological markers in order to measure both toxicity level and exposure to these chemicals

• Animal studies created to assess the effects of EDC exposure

• Developing ways to treat patients exposed to EDCs or learn ways to prevent exposure

When are Endocrine Disrupting Chemicals Most Dangerous?

Scientific studies show that EDC exposure produces the highest level of risk before a child is born, or in the period after birth in which the organs of the child's body are still developing. In animal studies, there are a number of different issues related to early EDC exposure, including increased cancer risk and reduced fertility, which may not become an issue until a much later point in the lifespan.

In one case, researchers found that animal subjects which were exposed to synthetic BPA or natural, human Estradiol during prenatal development as well as Estradiol during adulthood were much more likely to develop a particular prostate cancer precursor. This study provides evidence that both natural and synthetic estrogen exposure have the ability to impact the way that the prostate behaves at the genetic level, which increases the risk of prostate disorders and cancer.

Low Level Endocrine Disrupting Chemical Disruptor Exposure

Researchers have found that there is credible evidence that EDCs can impact the physiological function of animals even at very low doses. These doses are significantly below what has traditionally been believed to impact health and physiology.

Even though there has been a limited amount of study in regard to the direct impact of EDCs upon human health and function, the body of animal evidence is quite large, and Endocrine Disrupting Chemicals have the ability to cause the following issues in animal populations:

• Abnormal development of male reproductive organs

• Drop in male fertility

• Increased female-to-male birth ratio

• Increased incidence of sexual issues in female animals, including fertility complications and premature puberty

• Increased incidence of breast, prostate, and ovarian cancer

• BPA may also negatively impact diabetes and obesity.

Can Endocrine Disruptors in Pesticides and Plastics Affect Future Generations?

Evidence suggests that Endocrine Disrupting Chemicals not only have a negative impact on individual exposure, but EDC exposure may have a hereditary risk as well. There is some research that provides evidence that a patient exposed to Endocrine Disruptors may pass on their genetic abnormalities to future generations. In laboratory animals, the increased risk of cancer passed on three generations after initial exposure.

Another study found that male laboratory rats exposed to two particular EDCs were found to carry on abnormalities to almost every male in proceeding generations. The researchers hypothesize that these EDCs have the ability to alter gene expression without directly causing genetic mutation.

EDC research is a vastly expanding field, and as our knowledge of the effects of these chemicals continues to grow, it will help us to prevent or mitigate the effects of these chemicals on both human and animal populations.