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Written by Dr. Welsh, Article reviewed and edited by Dr. Fine M.D..
Published on 19 August 2014

Andropause FAQ

What is Andropause?

Andropause is a medical state that is a natural result of aging, in which symptoms of aging manifest resulting from a decline in Testosterone Production and other male hormones such as dehydroepiandrosterone, also referred to as DHEA.

Andropause is a universal factor of the male condition, although each male will physiologically react to the condition in their own way, and some men will display symptoms much earlier than others.

How Fast do Testosterone Levels Decline Over Time?

From the age of puberty to around the late twenties, males are flush with Testosterone, which contributes to optimal health and wellness. Around the late twenties or early thirties, however, these levels start to drop, at a rate of around 1%-2% per year. This decline is slow and without symptoms at first, but as the decline becomes more severe, the changes start to become apparent.

How Can I Qualify for Andropause Treatment?

In order to be prescribed Testosterone Treatment for Andropause, or other effective treatments, you must undergo clinical evaluation. Many men have Low Testosterone without displaying symptoms. In order to qualify for Low-T treatment, you must not only have clinically low levels of Testosterone, but you must also display symptoms of the condition.

There are many conditions which may prevent you from qualifying for treatment, including prostate cancer and severe sleep apnea.

What Blood Tests Are Necessary In Order to Diagnose Andropause?

Although your doctor may order a variety of tests in order to fully assess your overall health and hormone balance, for Age-Related Low-T, the most important test is the Free Testosterone Test. Free Testosterone is also referred to as Bioavailable Testosterone, and refers to the amount of Testosterone that is available for use by the body, and not currently being used.

With a saliva or blood sample, it is possible to take a snapshot of your current Free Testosterone Levels.

What is Total Testosterone?

Total Testosterone refers to all Testosterone that is circulating through your blood stream. This includes both Free (Bioavailable) Testosterone and bound Testosterone.

Why Is the Total Testosterone Test Insufficient for the Diagnosis of Andropause?

The vast majority of patients with Symptomatic Andropause have clinically normal Total Testosterone Levels, meaning that if Total Testosterone alone is evaluated, most patients with Andropause will appear to have normal Testosterone Levels, because the wrong factor is being measured. Recent research has shown that among men with Andropause, only 13% show depressed Total Testosterone Levels, whereas nearly three out of four of those patients had Low Free Testosterone Levels.

Because many physicians only measure Total Testosterone when evaluating Andropause, symptoms of Testosterone Deficiency are often diagnosed mistakenly as resultant from chronic fatigue, stress, depression, and other factors. Many of the treatments for these conditions actually have a depressant effect upon Testosterone, which could actually exacerbate symptoms in the long run.

By Fifty, What Percentage of Men Have Abnormally Low Free Testosterone Levels?

Among men over fifty, it is approximated that roughly half of men have Free Testosterone Concentrations that would be considered clinically low for men between the ages of thirty and forty.

What Are Other Names for Andropause?

Andropause is often referred to by a number of different names. For the sake of simplicity, it is often referred to in the media as Low-T, although Low-T is a broader term which simply refers to any physiological state in which Testosterone Levels are inadequate to meet the needs of the body. Another informal term for Andropause is Manopause, used to further emphasis the physiological connection between Menopause and Andropause.

Andropause is also sometimes referred to as Age-Related Testosterone Deficiency, which is a more adequate representation of the condition, because Andropause is an age-dependent chronic condition. Other similar names include Partial Androgen Deficiency in Aging Males, Androgen Deficiency of the Aging Male, and Symptomatic Late Onset Hypogonadism.

Because Andropause has not been fully accepted as a medical condition by the World Health Organization or the Food and Drug Administration, there is not a codified set of terms related to the condition, although there is a large amount of on-going study, and the condition is widely recognized by medical professionals and medical research institutes both nation- and worldwide.

What Causes Andropause?

Andropause is caused by a combination of hereditary factors and lifestyle choices, also known as Internal and External Causes. Internal causes are genetic.

Before Andropause occurs, the body enters a state of Hypogonadotrophic hypogonadism. During this period, the body produces less Testosterone than is produced by younger, healthier men. Hypogonadotrophic hypogonadism is a state in which the brain does not respond adequately to signals that Testosterone Levels are insufficient to promote the optimal health of the human body. Hypogonadotrophic hypogonadism generally takes place around the age of forty.

Testosterone production will continue to decline over time, eventually to a point at which the pituitary and the hypothalamus respond by producing elevated concentrations of Gonadotropin-Releasing Hormone and Luteinizing Hormone in an effort to rebound declining Testosterone. This is effective for a brief period of time, but the body eventually reverts to a state of decline once again.

This is the period at which Andropause takes place. Hypogonadotrophic hypogonadism refers to the early state at which GnRH and LH Levels are low in combination with Testosterone. Andropause refers to the period at which Testosterone Production remains inhibited in spite of increased LH and GnRH levels.

This hormonal change is absolutely normal, in that it is a natural progression of male hormone balance, which bears some similarities to menopause, hence the name. One significant way that Andropause and Menopause differ is that there is more variation as to when men begin to experience their change. Women will reach menopause at some point between the early 40s and late 50s, whereas some men will begin to experience symptoms before or even after that period.

What Are Lifestyle Factors Which Encourage Symptoms of Andropause?

Although the human body has a baseline of Testosterone Production dependent on age and genetics, this production can be affected by lifestyle choices which further suppress Testosterone Levels in the body. The following are some factors which can inhibit the body's natural ability to release Testosterone:

  • Inadequate Sleep

  • Poor Diet

  • Sedentary Lifestyle

  • Medications

  • Overindulgence of Alcohol

  • Stress

  • Illness

What Are the Symptoms of Andropause?

Andropause is a complex condition which affects male health in a wide variety of ways. The following are some symptoms associated with Age-Related Testosterone Deficiency:

  • Insomnia

  • Head and Back Aches

  • Reduced Sex Drive

  • Depression

  • Mood Instability

  • Hot Flashes

  • Hypersensitivity

  • Irritability

  • Social Withdrawal

  • Anger

  • Unhealthy Changes in Body Composition

  • Fatigue

  • Loss of Bone Mineral Density

What Are Some Effective Andropause Treatments Available?

Men with Andropause can benefit significantly from Hormone Replacement Therapy. There are a number of options available to Andropause patients, including:

  • Testosterone Patches

  • Testosterone Creams

  • Testosterone Gels

  • Injectable Testosterone (Testosterone Enanthate, Testosterone Cypionate, etc.)

  • Testosterone Pellet Therapy

  • Clomiphene Citrate

What is the Difference Between Andropause and Primary Testosterone Deficiency?

Most men suffering from symptoms related to Andropause have perfectly functioning testes, but do not receive sufficient signaling from the hypothalamus to produce enough Testosterone to meet the needs of the body.

Andropause is a form of secondary hypogonadism related to age. The older that men get, the less efficient that their bodies are at producing Testosterone. Primary Testosterone Deficiency is Low-T that is the result of a direct malfunction of the testes which prevents the body from being able to produce Testosterone at normal levels.

Both of these forms of Testosterone Deficiency can be treated with Bioidentical Testosterone Therapy, but there are more off-label options available to patients that suffer from Andropause and other forms of Secondary Hypogonadism, such as Clomiphene Citrate.

Testosterone production is actually the result of a cascade of signals that begins at the hypothalamus. The hypothalamus releases a hormone known as gonadotropin-releasing hormone (GnRH), which circulates to the pituitary, stimulating the production of Follicle-Stimulating Hormone and Luteinizing Hormone, which both contribute heavily to the healthy function of the male reproductive system. Luteinizing Hormone stimulates the production of Testosterone and other male sex hormones, while Follicle-Stimulating Hormone promotes the healthy production of sperm.

What Are Some Health Risks Associated with Andropause?

Andropause is correlated with a number of health conditions which can severely impact health and wellness, including:

  • Diabetes

  • Hypertension

  • Obesity

  • Chronic Fatigue

  • Heart Attack

  • Stroke

There is even evidence that Andropause leads to an increased risk of Alzheimer's and other neurological disorders.

What is the Goal of Andropause Treatment?

The ultimate goal of Andropause Treatment is not to flood the body with Testosterone, but simply to restore Testosterone Levels in the body to normal, physiological levels. In general, Testosterone Replacement Therapy Treatments aim to restore Testosterone Concentrations to what would be considered mid-normal for a man in his twenties.

In restoring Testosterone Levels to these physiologically normal levels, it is possible to significantly mitigate the symptoms of Andropause, helping men live healthier lives.

What Are the Benefits of Andropause Treatment?

  • Higher Quality of Life

  • Fewer Mood Swings

  • Reduced Irritability and Anxiety

  • Preserved Bone Mineral Density

  • More Energy

  • Enhanced Muscle Health

  • Increased Metabolism

  • Improved Capacity to Burn Fat

  • Increased Libido

There is preliminary evidence that shows that Testosterone Treatment also improves cardiovascular health, but more research is needed.

Does Andropause Treatment Cause Cancer?

There is no evidence that Testosterone Therapy for Andropause causes cancer, but the treatment can exacerbate existing forms of cancer, including breast and prostate cancer, and should not be prescribed to individuals that have or are at high risk of these or other forms of cancer.

How Can I Treat Infertility Related to Andropause?

Unfortunately, Testosterone alone is not capable of restoring fertility. This is because Bioidentical Testosterone actually suppresses the ability of the testes to produce Testosterone and sperm for the duration of therapy. This is temporary, and testosterone production will return after therapy has been suspended, but for patients interested in having children, Testosterone Treatment alone will not be sufficient.

Testosterone can, however, be combined with Human Chorionic Gonadotropin (HCG) in order to simultaneously increase Testosterone Concentrations in the body while simultaneously preserving fertility and the normal function of the Testes. In the male body, HCG acts as a functional analogue of Luteinizing Hormone, both preserving the body's ability to make some of its own Testosterone while also preserving the fertility of the patient.

Clomiphene citrate (brand name: Clomid) is sometimes prescribed to men with Testosterone Deficiency/Andropause that are interested in Testosterone Restoration which also preserves fertility. Clomiphene increases Testosterone and Sperm Production by inhibiting negative feedback mechanisms which can limit the healthy production of Testosterone.

Is It Possible to Use Erectile Dysfunction Medications During Andropause Treatment?

Yes, but you may not have to in the long run. Andropause is one of the main causes of Erectile Dysfunction as men grow older, and many men with Age-Related Testosterone Deficiency report that as a result of Testosterone Replacement Therapy, they no longer rely as heavily on Erectile Dysfunction Medications. Many patients even report that they no longer need to use such medications.

There is research that shows that taking Erectile Dysfunction medications with Testosterone Therapy has the ability to resolve ED issues in 95% of patients.

What Are the Potential Side-Effects of Testosterone Therapy for Andropause?

As with any form of medical treatment, there are risks associated with Testosterone Restoration. The following are some of the risks associated with Andropause Treatment:

  • Oily Skin, increased prevalence of acne

  • Male-Pattern Baldness

  • Headaches

  • Prolonged/Frequent Erections

  • Gynecomastia (increased breast tissue can be treated with estrogen-blockers such as Arimadex)

  • Increased Red Blood Cell Count (can be treated via blood donation)

  • Accidental long term overdose can lead to Heart Disease

All patients that take Testosterone will experience the following symptoms resulting from therapy:

  • Reduced Fertility

  • Testicular Shrinkage

These symptoms are temporary, and will slowly return to a normal state after treatment has ended. Combining Testosterone with HCG can prevent these symptoms, as can Low-T Treatment with clomiphene citrate.

How Can I Mitigate the Effects of Andropause Through Lifestyle?

What Should I Avoid the Onset of Andropause Symptoms?

Stop Smoking and Using Tobacco Andropause has a negative impact on cardiovascular health, and smoking only exacerbates the risk of cardiovascular complications. Also, smoking reduces normal erectile function because nicotine encourages vasoconstriction, which reduces the ability of the body to rush blood flow to the potential erection.

Don't Abuse Alcohol Alcohol promotes the body's production of estrogen, which depresses testosterone production. Also, alcohol reduces zinc levels in the body, which reduces the ability of the body to adequately control estrogen production.

What Should I Do to Delay the Onset and Severity of Andropause Symptoms?

Lose Weight Adipose body fat has the natural ability to promote elevated estrogen levels which suppress testosterone production in men. By losing weight, it is possible to promote a healthier testosterone balance.

Eat Healthier Your body also needs a well-rounded diet rich in nutrients in order to promote optimal hormone balance and mitigate the effects of Andropause. Although the body needs some fat, diets that are high in fat will expose the body to more estrogen. Also, organic foods can help improve Testosterone levels, because many common pesticides have estrogenic qualities. Finally, a diet rich in cruciferous vegetables such as cauliflower and broccoli promotes healthy testosterone balance as a result of naturally occurring antioxidant compounds such as indole-3-carbinol.

Make a Concerted Effort to Improve Sleeping Habits The body produces Testosterone primarily at night. By taking the steps to make sure that you get all the sleep your body needs, you protect your body's natural ability to produce Testosterone.

Take Zinc Supplements Zinc is a very important nutrient which promotes the body's ability to produce its own Testosterone while also inhibiting the body's ability to produce estrogen and other aromatase compounds which suppress Testosterone production.

Manage Stress More Effectively In order to promote healthy Testosterone Production, it is important to control one's stress. Stress increases the production of cortisol, which is another cholesterol-based hormone. The body has a limited amount of these resources, and if you have too much stress, your body will divert resources from Testosterone production to Cortisol production.

What is the Average Dosage for Testosterone Restoration for Andropause?

When men are in their twenties, they generally produce between four and seven milligrams of Testosterone. Because not all Testosterone is absorbed during topical Testosterone Therapy, the initial dosage is generally between ten and twenty milligrams each day in order to bring Free Testosterone Production back to normal.

Because of potential issues related to elevated Testosterone Levels, it is prudent to start with a small dose in order to provide benefits with the lowest risk of side effects. Generally, patients will stay on this starter dose for around three or four months, then come back for further evaluation. Their dose will remain the same or be adjusted based on further testing as well as an evaluation of the effectiveness of treatment.


Andropause: The Male Menopause


Frequently Asked Questions about Andropause (Male Menopause) and Testosterone Replacement Therapy


Wikipedia: Andropause



Written by Dr. Welsh, Article reviewed and edited by Dr. Fine M.D..
Published on 19 August 2014

Ghrelin Hormone Guide

What is Ghrelin?

Ghrelin is the primary hormone in the human body which regulates the sensation of hunger. It is considered a partner to a hormone known as Leptin, which controls satiation. Whereas Leptin is produced primarily by adipose fat tissue, Ghrelin is released by special cells throughout the digestive system. After Ghrelin is released, the hormone circulates through the body and activates at sites throughout the nervous system, in particular, the hypothalamus.

Like Leptin, in addition to impacting hunger signals, Ghrelin also has a role in metabolism and the usage and storage of energy.

When is Ghrelin Released?

Ghrelin is produced by the stomach when the stomach is empty, and the release of the hormone is suppressed when the stomach is stretched. The primary influence of Ghrelin is upon the hypothalamus, where it triggers the sensation of hunger and encourages the stomach to release acid in preparation of its next meal. It also readies the entire digestive system to process and move food through the system.

Leptin and Ghrelin both trigger activity upon the same receptors in the hypothalamus, although Ghrelin encourages hunger and Leptin suppresses it.

Ghrelin also alters the sensitivity of a certain pleasure center of the brain known as the ventral tegmental area, an area which plays a major role in both addiction and sexual libido. In particular, Ghrelin has a powerful influence on both acetylcholine and dopamine production.

Ghrelin is just one of many hormones that help human beings (and other animals) establish a routine pattern of energy distribution. It encourages the body to intake calories which will be converted into energy by stimulating hunger, and also alters the way that the body uses energy, in terms of immediate heat generation, adipose fat storage, and the process of the ATP cycle.

Ghrelin and Leptin Ideally Create Metabolic Homeostasis

When Ghrelin and Leptin are interacting as they should, it helps to promote an ideal physiological state, but when these hormones get out of their natural rhythms, it can lead to increased body weight and reduced metabolism, as well as powerful sensations of hunger which encourage eating junk food and other foods dense in calories.

Leptin controls the way that the body responds to food via signals from body fat, while Ghrelin controls the way that the body responds to food from the stomach itself. There are a number of pathways through which Ghrelin achieves this, some of which are not fully understood at this time. There are also synthetic molecules which imitate the function of Ghrelin which have the ability to both promote weight gain and increase appetite by activating receptor sites on the arcuate nucleus.

Insulin, Leptin, and Ghrelin

The ability of Ghrelin receptors to accept stimulation is affected both by the influence of insulin and Leptin. Also, Ghrelin encourages eating full meals because it suppresses the body's ability to feel the stomach stretch until toward the end of the meal when Ghrelin levels decline.

In addition to directly controlling hunger, Ghrelin also promotes the release of pleasure hormones which encourage an individual to regularly eat, but can also promote overeating as well as addiction if a patient lacks willpower and self-control. In fact, alcohol dependency requires Ghrelin to activate receptors on the hypothalamus, and this is also one of the influences which encourage people to prefer certain foods over others.

Ghrelin and Eating Habits

Ghrelin is a powerful hormonal force which controls both feeding and appetite in animals, including humans. Ghrelin levels drop after we eat a meal, and slowly rise over time, increasing our hunger and desire to eat. Ghrelin peaks immediately before eating and drops to its lowest levels after the meal has concluded.

Ghrelin Injections, and the injection of Synthetic Ghrelin Analogues, have the ability to increase hunger and appetite dependent upon the dose of the hormone that is administered. This means that the more Ghrelin that is administered, the more calories that a patient will consume over time. This does not make individuals eat more at every meal, however. It makes them become hungry again much more quickly than they normally would, so they eat more meals each day.

In animal species, the administration of Ghrelin causes the animal to search for food more aggressively, and increases the prevalence of any activities related to meal habits, including hoarding, foraging, or sniffing out food.

Ghrelin and Metabolism

Body mass is controlled through metabolism. At its simplest, this simply means that weight is controlled by adjusting how calories are taken in and how calories are burned from day to day. The more Ghrelin that an animal produces, the more they will weigh, as a general rule. Based on this information, it is believed that Ghrelin acts as an intermediary between adipose fat deposits and the brain.

Ghrelin is dependent upon the weight of the individual. The less than a person weights, the more Ghrelin that their body will produce, while on the other hand, the more that a person weighs, the less Ghrelin that they will produce. This may be one reason why many people that are overweight don't eat as often as their peers, but eat larger meals as a result of their lack of self control.

Under normal circumstances, Ghrelin works in the body as a means to keep weight at an average healthy level, mediating the body's use of energy and its mass.

Ghrelin and the Digestive System

Ghrelin acts as an anti-inflammatory in the digestive system and prevents cells from spontaneously dying during times of internal stress and inflammation. Ghrelin generally promotes the activity of other anti-inflammatory hormones and compounds while limiting the activity of those that cause inflammation. For this reason, researchers hypothesize that medically administered Ghrelin may one day be useful in promoting gastrointestinal health during these times of stress. Ghrelin also appears to help the interior of the digestive system rehabilitate itself after damage and injury.

In the case of pancreatic and gastrointestinal cancers, elevated Ghrelin levels can exacerbate the illness.

Ghrelin and the Pancreas

Ghrelin and insulin are related hormones, and the presence of one impacts the activity of the other. There are Ghrelin receptors on the pancreas, and when Ghrelin activates these points, it slows down the release of insulin in response to the presence of glucose. This means that Ghrelin slows down the rate at which the body processes sugar as it circulates through the body.

Ghrelin and Heart Health

Ghrelin is beneficial to heart health because it inhibits the formation of fatty deposits in the arteries, and it also encourages the healthy function of the endothelium, the inner lining of the blood vessels.

Ghrelin, Memory, and Learning

The hippocampus is the center for learning in the brain. Ghrelin plays a role in all of this, and also encourages the production of Human Growth Hormone. Ghrelin circulates through the blood stream and passes through the blood-brain barrier at the hippocampus, and encourages the development of new connections in the brain

There is some evidence that the brain is able to retain information at the highest levels when Ghrelin levels are higher, which means that when people are full, they may have slightly more trouble learning than when they are hungry. From an evolutionary perspective, it does seem beneficial to have additional horsepower in the brain when the body requires food, and for the mind to slow down after a meal has been found and consumed. This process is apparent in animal studies, and it is hypothesized that in humans this same mechanism is at play, at least to a certain extent.

Ghrelin and Depression

Animal research has shown that Ghrelin promotes a healthier psychological profile and inhibits depression. Lab mice which don't produce Ghrelin experience greater levels of anxiety when they are exposed to both physical and psychological stress. Under normal circumstances, Ghrelin has the ability to interact with the hypothalamic-pituitary-adrenal axis in a way that reduces the effects of stress.

Also, animal studies have shown that Ghrelin acts like an anti-depressant in laboratory mice, as rodents with elevated levels of the hormone showed fewer signs of stress than their peers without Ghrelin. Furthermore, rodents that were unable to produce Ghrelin were less likely to interact with other rats around them.

When these lab rodents were provided an anti-depressant, it counteracted the social inhibition experienced resulting from a lack of Ghrelin, which suggests that Ghrelin helps ward off depression by some underlying mechanism.

Ghrelin and Sleep

Elevated Ghrelin Levels are associated with shorter periods of rest, and this is also associated with being overweight. The more Ghrelin that is present in the blood stream, the less sleep that an individual will experience. Also, those that sleep well through the night are less likely to experience obesity, and their Ghrelin levels tend to be lower.

Ghrelin and Fear Response

Humans and animals have a tendency to experience latent fear as a result of past experiences of stress. Ghrelin plays a role in this, as the body releases Ghrelin in response to such fear, which makes the source of the fear easier to retain. Stress affects Ghrelin concentrations even when the body is not producing adrenal hormones such as cortisol. When Ghrelin stimulation is inhibited, this suppresses the brain's tendency to learn what to fear more effectively under stress, although it does not affect adrenal response to stress.

In the future, there will likely be medications that use synthetic Ghrelin or Ghrelin analogues as a means to limit the effects of mental disorders caused by stress.

Ghrelin and Dopamine

Dopamine is the primary pleasure hormone that is produced by the body. Ghrelin increases the level of dopamine that is present in the substantia nigra, which is the reward center of the brain. Upon eating or engaging in any other pleasurable activity, this enhances the sensation of pleasure.

Ghrelin and Reproductive Health

Ghrelin inhibits the release of precursor hormones which produce sex hormones and sperm, whereas Leptin encourages the production of these hormones. It is unclear to what extent that this may limit fertility. From an evolutionary standpoint, it makes sense that during times of hunger, reproduction would be a secondary concern, whereas during periods of satiation and abundance, sex drive and function would increase.

Prenatal Health and Ghrelin Production

During the fetal stage, the developing lungs produce Ghrelin in order to accelerate the growth of the organ. Also, there is a connection between the concentration of Ghrelin in the umbilical cord and the weight of the child at birth.

Ghrelin, Obesity, and Anorexia

As we mentioned earlier, individuals that are overweight or obese do not produce as much Ghrelin as their thinner counterparts. For this reason, it does not seem that Ghrelin is a contributor to weight gain, although its high or low levels can affect other aspects of physiological health. The exception to this is patients that suffer from Prader-Willi syndrome. Among these patients, Ghrelin levels do promote obesity.

Individuals that suffer from anorexia have exceptionally high blood-concentrations of Ghrelin. The issue is that their bodies override these normal physiological cues to eat. Clinical research has shown that by introducing exogenous Ghrelin intravenously, it is possible to increase calorie intake among patients with anorexia by as much as 36%.

Under normal, healthy circumstances, Ghrelin levels are low around bedtime and increase slowly through the course of the night. Overweight and obese individuals are more likely to experience elevated Ghrelin levels at inappropriate times, which is evidence toward the hypothesis that obesity is a condition that is exacerbated by an incorrect circadian rhythm.

Being in front of a computer screen or other source of abundant light during the late evening can interrupt the natural rise and fall or Ghrelin levels at night. Also, individuals that don't get enough sleep at night produce more Ghrelin, because sleep naturally has a depressant effect upon the hormone. Poor sleeping habits promote the suppression of leptin and the release of Ghrelin, which promotes overeating.

Potential Medical Uses of Ghrelin in the Future

  • Ghrelin may also prove to be an effective means to promote the normal muscle activity of the stomach in individuals suffering from gastroparesis.

  • In animal research, Ghrelin has proven effective at reducing the number and severity of seizures that afflicted animals experience. This may cross over into humans.

  • Ghrelin will soon be used as a treatment for many forms of wasting disease, and may assist patients being treated for kidney failure.

Ghrelin and Appetite: A Research Study

New research shows that elevated levels of Ghrelin promote poor dietary choices, which is why many people may be more prone to eating unhealthy foods packed with calories like cookies and cake.

Simply having elevated Ghrelin in circulation is as powerful of an influence on diet as the act of fasting, both of which encourage desire for calorie-dense foods. Ghrelin reaches very high levels during the act of fasting, but the administration of synthetic Ghrelin can mimic the physiological and psychological desires associated with such a fast, even if the patient does not engage in the activity.

This is because of the way that Ghrelin interacts with the reward centers of the brain. In this study, it was found that synthetic Ghrelin significantly increased the activity in the area of the brain which activates in response to pleasure.

The main researcher in this study, Dr. Goldstone, was interested in seeing how the administration of Ghrelin via injection compared to the act of fasting in relationship to dietary choice.

His study involved eighteen patients, all around the age of 23, all of which were of average weight. They were required to fast the night before and come in without breakfast, and they visited the medical location on three occasions, all of which were at least seven days between.

Each visit, patients either stayed on the fast or ate a meal of 730 calories. After they were fed or required to remain on their fast, they were administered with an injection of either Ghrelin or saline. In order to ensure that the patients' bodies reacted to the Ghrelin injection, they were tested for elevated HGH levels, which rise at the same time that Ghrelin Levels rise in the blood stream.

Ghrelin Research Procedures

Rather than eating after the injection, the subjects were shown various images of foods, sixty of which were low calorie foods, and sixty of which were foods with high calories. Interspersed among these pictures were photos of things seen around the house, to act as a control. During this rating process, their brains were scanned in an MRI machine, meaning that the patient could both provide a qualitative response while the researchers also measured the neurological response to the food stimulus.

How Does Ghrelin Affect Desire for Food?

What researchers discovered was that Ghrelin had no effect on the participants' interest in foods with low calories, while it did increase the desire for foods with a lot of calories. In particular, Ghrelin increased the desire for sweets the most.

One particular area of the brain that was closely monitored during these tests was the anterior orbital frontal cortex, which is the location of the brain that stores the desire that the brain has for particular foods. He found that satiated individuals that received saline did not experience high levels of activation in this area, whereas those that received Ghrelin still experienced activity in this area even when the patient was fed prior to the imaging session.

Does Ghrelin Contribute to Obesity?

Ghrelin may not directly cause obesity, but it does prevent the body from changing its pattern of nutrition intake. Ghrelin levels remain low as long as the obese patient stays at his or her stable weight, but as soon as he or she tries to lose the weight, Ghrelin levels increase dramatically. It is believed that one day, there will be treatments available which block the body's production of Ghrelin during dieting in order to promote weight loss and treat obesity.


Hormone Ghrelin Ups Desire for High Calorie Foods


Wikipedia: Ghrelin


Your Hunger Hormones: How They Affect Your Appetite and Your Weight



Written by Dr. Welsh, Article reviewed and edited by Dr. Fine M.D..
Published on 19 August 2014

Leptin Hormone Guide

What is Leptin?

Leptin is a hormone that has many purposes, but primarily it is responsible for the full sensation that we get after the body decides that we've had enough to eat. It is frequently referred to as the “satiety hormone.” Leptin is released by fat cells in an effort to control the way that our body stores fat. In addition to suppressing hunger, leptin also alters the way that our body uses energy.

The fat cells release leptin when they have stored a certain level of fat converted from the calories from the food that we eat. When leptin is released, it enters the blood stream and passes through the body. Leptin travels through the cardiovascular system to the hypothalamus, where it activates special receptors in the arcuate nucleus.

When leptin receptors are activated, it causes the body to increase metabolism, while also reducing signals for hunger. Although this is primarily affected through the brain, there are targets throughout the body which are also responsible for increasing metabolism.

The two hormones, Leptin and Ghrelin, have opposite, component effects upon the body. Whereas leptin controls the feeling of satiation, Ghrelin controls the sensation of hunger. Leptin and Ghrelin receptors are actually located on the same cells, and are two vital hormones responsible for the way that our body both stores and expends energy.

Leptin has a number of different purposes in the body, but the most important of these is considered the regulation of the way that the body stores fat. Our knowledge of how Leptin works is far from complete, but leptin is produced not only by fat cells, but by other organs as well.

Where is Leptin Produced?

The majority of leptin is secreted by white adipose fat tissue by organelles known as adipocytes. Leptin is also secreted from other locations, including the liver, pituitary, bone marrow, epithelial cells, stomach, skeletal muscle, ovaries, placenta, and brown adipose fat tissue.

What Causes Leptin Levels to Fluctuate?

Like other hormones such as Testosterone, Leptin flows through the blood stream both locked into a carrier protein and freely. Because body fat produces leptin, the more body fat that a person carries, the more leptin that they will produce. Perhaps surprisingly, the amount of leptin produced by body fat increases exponentially with the volume of body fat that a person carries.

Leptin concentrations also follow the circadian rhythm under normal circumstances. From around 12am to some point in the early morning, leptin levels remain quite high, which is believed to prevent hunger and promote sleep. Although this is the normal pattern of leptin release and circulation, if a person eats at odd times, such as in the middle of the night, this alters the rhythm of leptin release.

There are many ways that Leptin production is unrelated to body fat as well:

  • Fasting for one to three days leads to a drop in Leptin production, even if body fat remains the same. Related to this, Leptin levels also drop as a response to starvation, encouraging hunger even when the body still has a large amount of body fat. This is actually one reason why crash diets don't work effectively. Starving yourself will eventually cause you to lose weight, but once you lose the weight, your body will not be able to effectively send signals for satiation, causing you to eat more than your body needs and experience hunger even though you are eating a healthy diet.

  • Psychological stress increases Leptin Production.

  • Leptin is affected significantly by sex hormone concentrations in the body. Testosterone is associated with reduced leptin, whereas estrogen is associated with increased leptin. Some hormones released in response to stress, including dexamethasone, also increase leptin secretion.

  • Physical training will cause leptin levels to drop for the duration of time that a person engages in a healthy exercise routine. This makes sense, because physical exercise stimulates metabolism and increases the need for calories to maintain a certain weight.

  • The more insulin that your body produces, the more leptin that your body will produce.

  • For complex reasons, obesity actually leads to an increase in Leptin production.

  • Overweight individuals with obstructive sleep apnea experience increased leptin levels, but CPAP treatment can bring leptin production back to more normalized levels. Short-term sleep deprivation can lead to a reduction in Leptin production, but long term issues with sleep deprivation, such as sleep apnea, can increase leptin concentrations.

Effects of Leptin

After Leptin is released by body fat and other cells, it suppresses hunger primarily through three mechanisms:

  • Encourages the production of α-MSH, which suppresses hunger.

  • Blocks the activity of anandamide, a hormone which encourages hunger via the same mechanism as THC present in marijuana.

  • Blocks the activity of Neuropeptide Y, a molecule released by the hypothalamus and the stomach which encourages hunger.

In spite of the fact that leptin is the hormone that we most associate with hunger, it is actually only responsible for long-term appetite control. Other hormones are responsible for short term and intermediate hunger:

  • PYY3-36 is the reason why we don't feel hungry between meals. This hormone encourages us to eat our meals during single sittings.

  • Cholecystokinin is the hormone which is produced as we eat which inhibits hunger signals. This hormone helps us know when we are full at a particular meal.

Of course, leptin does play a role in the way that these hormones function. Animal research involving leptin clearly shows how the hormone contributes to diet control, as animals which have their ability to produce leptin removed gain weight uncontrollably as a result of a loss of their ability to become full.

Caloric restriction and fasting both have an inhibitive effect upon the production of Leptin. In addition to this, the body is more reactive to the absence of food, rather than its overabundance, so Leptin production will change faster and more dramatically when the body is not getting enough food. This also means that once food access is restored, hunger response won't return to normal as quickly as it was first altered.

Changes in leptin production resulting from abrupt changes in food access appear to be correlated with changes in food intake and diet rather than the energy available that is locked in body fat. This means that leptin suppression due to hunger is not mitigated by existing body fat.

How Does Leptin Control Diet?

Leptin encourages eating and changes in metabolism by triggering receptors in the mediobasal hypothalamus. It used to be believed that blood sugar directly controlled metabolism and eating patterns, but it is clear today that leptin is the mediator of this process.

As we mentioned earlier, Neuropeptide Y activity encourages hunger. There are neurons which produce this hormone in the arcuate nucleus, and as leptin passes through the body, it binds to these neurons, preventing the release of this potent hunger hormone, promoting a disinterest in food. There is also evidence that when Leptin levels are in balance, this makes it easier to eat a healthy diet and not be tempted by the allure of calorie-dense foods.

Prior research has shown that Neuropeptide Y plays an important role in the way that animals eat, including humans. When Neuropeptide Y is artificially introduced to the brain, it automatically triggers the animal to seek out food. The opposite is also true. If the neurons which produce Neuropeptide Y are destroyed, the mice ill become disinterested in eating and become drastically underweight.

Leptin also encourages the release of a peptide known as α-MSH which promotes the feeling of satiety, and genetic abnormalities which limit α-MSH have been shown to increase hunger response and increase the risk of obesity considerably.

Melatonin Affects Leptin Production

In a vacuum, elevated melatonin leads directly to reduced production of leptin. On the other hand, if insulin is in circulation, melatonin leads to an increase in leptin production. This interaction is important because it prevents us from becoming hungry while we are asleep, which can disturb sleeping patterns.

This is why it is generally encouraged to eat a healthy dinner a few hours before bed. This way, your stomach isn't full while you are asleep, but your digestive system is still somewhat active, which means that you have insulin and melatonin in your blood stream, which encourages healthy sleep.

By the end of the night, when insulin levels drop, Leptin levels start to fall as well, as melatonin levels are still elevated. This, in combination with an increase in cortisol and other factors, helps set the stage for you to wake up refreshed and hungry.

Leptin and Diabetes

Preliminary animal research shows that combining leptin with insulin improves metabolism and stabilizes blood sugar more effectively. This combination also helped promote healthier body composition while also balancing cholesterol.

Leptin and the Cardiovascular System

Leptin has an impact on the activity of T-Cells in the immune system. Leptin promotes the health of the heart tissue and healthy leptin levels reduce the inflammatory activity which promotes atherosclerosis. There is also evidence that elevated Leptin levels can help control blood pressure if prescribed medically.

Leptin and the Reproductive System

Leptin does not play any predominant role in human fertility, but it is important and necessary to create the conditions which promote fertility. The regularity of the menstrual cycle depends upon proper metabolism, and is dependent upon the normalized flow of energy through the body, which leptin plays a part in regulating.

If a woman frequently enters a state of starvation, whether purposefully or unintentionally, the menstrual cycle will go into dormancy. Also, if a woman engages in heavy exercise, they also risk entering this state, even if they consume enough calories to meet the demands of their body. On the other hand, menstruation is only affected by low body mass in extreme cases.

In both sexes, Leptin encourages the hypothalamus to produce Gonadotropin-Releasing Hormone, the precursor to Luteinizing Hormone and Follicle-Stimulating Hormone necessary to encourage both sex hormone production as well as sperm production.

Leptin and Pregnancy

During pregnancy, leptin is produced by the placenta, and it continues to be produced in greater concentration throughout pregnancy before returning to baseline after the child is born. This is because leptin has an inhibitory effect upon contractions, allowing the child to develop within the womb. When leptin levels fall, this encourages contractions and helps to stimulate childbirth. Elevated leptin levels also contribute to the condition of morning sickness that commonly takes place during pregnancy.

Leptin and Puberty

There are two hormones which determine when an individual enters puberty: kisspeptin and leptin. In the period just before puberty, leptin levels start to rise, and once they reach a certain point, puberty is triggered. Childhood obesity can lead to early puberty, because adipose fat cells produce leptin, and cause leptin levels to reach the triggering point much faster than in children with normal levels of body fat. There is also evidence that girls that enter puberty early don't grow as tall as their peers, because the increase in estrogen production promotes the closure of the growth plates.

Leptin and Bone Mineral Density

Leptin also appears to help promote healthy bone mineral density. When the brain receives sufficient satiation signals, it then signals the bones to undergo metabolic changes which promote cortical bone growth and inhibit cancellous bone. Cancellous bone is the softer tissue in the core of the bone, and cortical bone is the hard casing which covers the cancellous bone. Thus, leptin plays a role in bone maturation during puberty because the bones become thicker and harder, allowing them to carry more weight.

After puberty, leptin still plays a role in bone metabolism, because once it activates at its receptor sites on the hypothalamus, is alters the production of a number of other hormones and peptides associated with the regulation of bone mineral density. There is also some evidence that Leptin directly contributes to increased bone mineral density by playing an intermediary role between metabolism and the release and activation of Insulin-Like Growth Factor-One. As a result of this connection, there may be treatments in the future which utilize leptin in order to enhance the natural healing processes of bone tissue after breaks and fractures.

Leptin and the Brain

Although the primary trigger point for leptin is the hypothalamus, there are also receptors for the hormone at other locations within the brain. One of the largest receptor sites outside of the hypothalamus is the hippocampus.

Research has clearly shown that Leptin Deficiency has a negative impact on the normal function of neurons as well as brain proteins. In animal studies, normal neurological function in this instance can be restored by providing injections of leptin.

In humans, Leptin Deficiency is associated with neurological and cognitive changes that are associated with HIV, depression, and anorexia. There is even evidence in rats that leptin deficiency may play a role in Alzheimer's, and that providing leptin therapy may be able to increase cognitive ability and reduce the negative effects of the disease by limiting the concentrations of hyperphosphorylated tau and b-amyloid, which are two of the main factors which make Alzheimer's such a devastating neurological disorder.

Leptin and the Immune System

Leptin is intricately related to the immune system response of inflammation, and leptin has a regulatory effect upon a number of factors which affect immune health, including body fat, caloric restriction, stress, sleep, and Testosterone levels. It is hypothesized that the primary mechanism which links Leptin to immune health is that Leptin helps control the activity of cytokines released by adipose tissue.

Leptin is actually structurally similar to cytokines both in function and its molecular composition. There is evidence that Leptin plays an active role in the way that the body handles and manages stress, but the direct mechanisms are not completely understood. There is also a positive correlation between white blood cell count and leptin levels.

Diseases Associated with High Leptin Levels

There are a number of medical conditions which are associated with abnormally high leptin levels, especially those associated with inflammation. Among these are cardiovascular disease, chronic fatigue, and hypertension.

Elevated levels of leptin are correlated with overeating, the mass of adipose fat cells, and overall body composition, but leptin is not connected in any way to physical activity. Exercise does not stimulate or suppress the production of leptin directly. For this reason, it is hypothesized that leptin is designed to activate only with regard to inflammation related to adipose fat. Leptin promotes the formation of new blood vessels, promotes inflammation, and encourages cellular metabolism.

Based on these factors, it is believed that the elevation of leptin levels due to overeating is a mechanism designed to limit the stress on fat cells caused by abrupt changes related to increased caloric intake. When the fat cells no longer have enough room to absorb all the calories being delivered, this causes the body to begin to store fat in the muscles, arteries, and organs, which is dangerous.

So in this sense, leptin triggers satiation in order to prevent the body from eating so much that the fat cells can no longer make room for it all, but obesity causes the body to produce too much of the hormone, which can have negative effects. Like other inflammatory/stress hormones, the body needs leptin, but there are serious issues which can result when the hormone is allowed to remain at abnormally high levels for too long.


The Facts on Leptin: FAQ - The Truth about the Hormone Leptin and Obesity


Serum Leptin Levels in Males with Delayed Puberty during Short-Term Pulsatile GnRH Administration.


Wikipedia: Leptin


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