@loopy107 2903 wrote:

I’ve consistently had low igf-1 levels (120-150) for a few years now even when on trt, thyroid, and adrenal meds.

The highest I got my igf-1 was around 216 while on all these meds, but haven’t got back to those numbers.

Now that I’ve come off trt 7 months ago and my igf-1 has dropped into the 90’s range and t-levels are at 423, shbg is 14 post recent clomid therapy.

I also have insulin resistance and neurotransmitter deficiencies in dopamine and serotonin (neuro problems since childhood).

Does these levels warrant HGH therapy?

I’ve had symptoms of low GH since at least high school 14-15 years ago. I stopped playing sports as soon as I got into high school because I felt my joints became very weak and felt my ankle were going to break when running. I would feel shocking pains in my ankles. I also diet very well for my insulin resistance but no matter how much cardio I do I can’t lose any weight.

Could the weight issue be cause by low HGH?

What type of testing needs to be done to determine if it is HGH?

The Endocrine Society has a useful guideline for growth hormone deficiency diagnosis and treatment.

Quest Diagnostrics Labs has the adult range for IGF-1 (an indirect measure of growth hormone) as:
Males 19-30 y.o. : 126 to 382 ng/mL
Females 19-30 y.o.: 138-410 ng/mL

Where a practitioner draws the line on where growth hormone deficiency lies depends on the practitioner. Since many anti-aging doctors aim to optimize levels, for example, their cut-off point may be higher than others for what is deficient. They may aim for a level close to 400 ng/mL. Per Endocrine Society guidelines, even a normal IGF-1 does not preclude growth hormone deficiency, though additional testing needs to be done in this case, to verify a growth hormone deficiency. There is a lot of clinical consideration to the diagnosis.

Aside from IGF-1, a 24-hour urine growth hormone test can be done as well as individual blood tests for growth hormone, and stimulation tests for growth hormone. How much testing needs to be done depends on the practitioner.

IGF-1, which does the bulk of growth hormone’s actions, is also influenced by many factors. This includes signals such as testosterone, thyroid hormone, insulin, DHEA, cortisol, dopamine, norepinephrine etc. etc. Signaling problems, metabolic problems, and nutritional problems can all lower growth hormone production. Optimizing these other signaling systems, metabolism and nutrition will help increase growth hormone’s effectiveness, and IGF-1. Ultimately, optimizing these systems first both increases one’s own growth hormone production and reduces the dose for growth hormone needed when treatment is decided, if it is needed at all.

Thus, why should a person be treated with growth hormone if they are still hypogonadal, hypothyroid, have insulin resistance or diabetes, immune problems, have poor nutrition or nervous system/mental health problems? These will reduce growth hormone production. Many symptoms attributed to low growth hormone (aside from impaired skeletal growth – which is too late to be treated once adult) may instead represent problems in other systems which influence growth hormone. These problems ideally should be addressed first before growth hormone treatment.

Generally, growth hormone should be the last treatment considered. The other signaling system, metabolism and nutrition may need to be first optimized. This would help minimize problems from adding growth hormone itself.

Side effects of growth hormone may include: fatigue, joint stiffness, water retention, joint pain, muscle pain, carpal tunnel syndrome, hypertension, insulin resistance and Diabetes type 2, up to 30% reduction in adrenal function (including lower cortisol, progesterone, testosterone, estradiol, DHEA production), lower thyroid hormone levels. Optimizing the affected systems may help buffer and reduce side effects of treatment.

Many practitioners prefer to add growth hormone at the start since the incidence of side effects is relatively low. But I usually get to see the patients when growth hormone did not work and instead worsened their condition since the other systems were not first optimized. In these patients, I may have to remove growth hormone treatment and address the other underlying problems that cause their illness.

@loopy107 2918 wrote:

How does someone optimize both neurotransmitters in order to get GH levels up?
I have low dopamine (constantly spaced out) and low serotonin. Dopamine meds cause adrenal fatigue so how does someone get around that? I took adderall and felt like I was high and it beat up my adrenals.

Stimulants, such as Adderall, increase both dopamine signaling and norepinephrine signaling. The norepinephrine signaling may then increase inflammatory cytokine signaling, which then leads to dysregulation of the adrenal glands. One cannot separate the desired dopamine signal increase from the undesired norepinephrine increase when using a stimulant. Excessive norepinephrine signaling will reduce growth hormone production.

Improving nutrition can improve neurotransmitter signaling and growth hormone production. For example, optimizing iron (neither too high nor too low) helps reduce the need for norepinephrine signaling to improve metabolism and improves dopamine signaling. Some growth hormone secretagogues improve certain amino acids to improve growth hormone production. For example, Secretropin, a prescription growth hormone secretagogue attempts to use nutrients to improve growth hormone production – with research to back it up.

Optimizing endocrine and immune function can also do the same.

Certain medications can improve neurotransmitter signaling to help improve growth hormone production.

@loopy107 2934 wrote:

How can one really improve low dopamine and serotonin? What medications that are not stimulants that can help whether it’s one medicine that does both or a combo?

Both are low for me and even though my cortisol dose works for me I still don’t have any energy or motivation. The last time I had energy and could really work out was when my doc had me on adderall which fatigued me too much. Concerta and wellbutrin didn’t fatigue me that I can remember. I need to optimized both for sure. I grew up having an issue of not being able to feel love emotions. I feel very flat emotionally and never feel euphoric at any time that I’m happy.

To improve signaling, one has to improve metabolism and nutrition. This, for example, helps provide the precursors for the production of dopamine and serotonin, and helps the processes that form them. Dopamine production and other signals are dependent on optimal iron levels.

Increasing serotonin signaling is fairly easy and commonly done: Serotonin reuptake inhibitors increase the duration of serotonin signaling. Some people benefit from taking the precursor for serotonin – tryptophan or 5HTP. Increasing serotonin will reduce dopamine production, however. Thus a balance needs to be struck.

Increasing dopaming signaling in the behavioral areas can be done using dopamine agonists. When stimulants are too strong, a much weaker one such as Provigil can be employed, which doesn’t increase norepinephrine excessively.

Drive/motivation needs a combination of dopamine and norepinephrine. Dopamine alone can make a person sleepy or dizzy or constipated, etc. , particularly in excess.

Dopamine signaling, however, is reduced when there is excessive stress and inflammatory signaling in the body. The causes for these signaling problems have to be found and addressed in order to restore a feeling of wellness.

@loopy107 2938 wrote:

Can Provigil increase sex drive even while on SSRI? Another issue is that I need SSRI for serotonin, but can’t afford to gain weight because of my insulin resistance.
How does some one like me with insulin resistance get around the weight gain on SSRI especially if I have a hard time losing weight?

Even though I’m on HC tablets at 20mg per with dhea cream I still seem stressed not as much as before doing the dhea so it did help. I also diet very well with low carb diet and low glycimic foods, but continue to have insulin resistance issues and can’t lose weight not matter how much cardio I do or how well I eat. I though when I got on thyroid meds that I would lose weight, but I did not. Motivation is a big issue for me because of low dopamine.

Provigil may increase sex drive. Stimulants have long been used to increase sex drive. However, which direction is goes depends on the sum of the signaling and metabolic changes it triggers. By increasing norepinephrine in a person who already has excessive norepinephrine signaling, it may also just tip the balance toward impaired sex drive.

Being overweight or obese and having insulin resistance places one in a vicious circle or positive feedback loop. In obesity, the fat cells send signals to the body which lead to increased stress/norepinephrine signaling. The increased norepinephrine signaling causes insulin resistance, which leads to an increase in insulin signaling. Insulin is a signal that triggers fat storage.

Breaking this loop is difficult. Insulin resistance usually has many simultaneous underlying causes. Each has to be searched for and addressed. Suboptimal thyroid hormone signaling can lead to insulin resistance. Multiple nutrient deficiencies can lead to insulin resistance. The multiple causes of stress/norepinephrine signaling can lead to insulin resistance. Suboptimal testosterone signaling can lead to insulin resistance. Nervous system dysfunction can lead to insulin resistance. Immune system problems can lead to insulin resistance. etc. etc. etc.

Despite the subphysiologic dose of 20 mg a day, exogenous hydrocortisone – which is working against the factors that lead to adrenal dysregulation and lowered adrenal cortex signaling – can itself contribute to insulin resistance within that context. This is why it is important to search for and address the causes of adrenal dysregulation instead of settling for adrenal signaling support via hormone replacement therapy.

Often, when someone tells me they have a good diet, it turns out, after analyzing their diet, it is a poor diet. Most often, the diet is nutrient poor – missing several nutrients. One has to be care even with a low carb diet, for example. Tryptophan, the precursor to serotonin, which is one of the primary control signals for norepinephrine – i.e. it is one of the primary antistress signals, is not well absorbed without carbohydrates. One hallmark of a good diet is that it is nutrient dense. This reduces the need for a high calorie diet to obtain crucial nutrients. One does not need to eat much when the diet is nutrient dense.

One reason it may be difficult to reduce weight is that weight gain is a defensive response to stress. As I am fond of saying, “Stress causes weight gain” – predictably. Fat is stored energy. Muscle can be also considered stored energy. This is one reason I like to keep track of a patient’s weight. When weight goes up, generally, the patient has had a stressful period of time. In my experience, in only perhaps 1 in 9 people does stress cause weight loss. In the others have weight gain, instead. The presence of excessive stress/norepinephrine signaling indicates something continues to be wrong either externally (e.g. environmental stress, relationship stress, job stress, etc.) or internally to the body. It is important to target the internal causes of stress (e.g. infection, nutrient deficiency, hormone deficiency, etc. etc.).

@loopy107 2949 wrote:

I though when I got on thyroid medication for hypothyroidism that I would of lost weight or had an easier time, but that was not the case. obvious something is out of whack and not normal. I also know that my lipids are messed up and I’m pretty sure I have high
triglycerides, but sure what causes it or how to fix it.

I’ve also grown up with a bit of a social disorder when I’m around groups of people I speak only when I have to and trying to be an out going person and talkative with people I meet or don’t know is impossible. I am talkative with people I’m comfortable with, but more reserved around new people. My doc had put me on adderral to help that, but it made me feel high and made it worse to talk to people. I guess the brain fog makes it harder to process quick thoughts and makes me less likely to be talkative. I also constantly have to shake my legs when sitting down. Been like that since childhood and would need to pace around if I was standing.

Can Provigil and a SSRI help that social disorder and leg shaking?

Weight gain has multiple possible causes which can all be present in a person. Thus, hypothyroidism can be one of many causes a person may have. Each cause needs to be identified and addressed in order for a person to lose weight. Some causes include:
1. Hypothyroidism
2. Poor nutrition (e.g. low nutrient density, low animal fat content, excess carbohydrates, food choices, etc.)
3. Stress – both external (e.g. work, relationship, psychological problems, social issues, etc.) and internal (e.g. metabolic problems, infection, nutritional deficiencies, etc.).
4. Insulin Resistance (which has multiple causes including hypothyroidism, stress, poor nutrition, low testosterone, suboptimal lipid metabolism, etc.)
5. Excessive Caloric Intake compared to caloric needs (e.g. lack of exercise or physical activity, etc.)
6. Genetic factors (including hypothyroidism, etc.)
7. Etc.

From a societal point of view, much of obesity is due to poor nutrition. This tends to follow socioeconomic factors – with poor people tending to be obese since they are forced to eat more affordable but non-nutrient dense foods. But the lack of nutritional density can be applied to various people in regard to food choices. And this contributes to obesity.

One alternative way of looking at obesity is that people will eat in excess of their caloric needs in an attempt to meet nutrient deficiencies at the cellular level. These nutrient deficiencies will drive behavior to find a solution. If society provides non-nutrient dense food choices, then caloric intake will inevitably be in excess. Historically, societies have moved away from nutrient-dense traditional foods for less nutrient-dense modern foods for various reasons, at its peril.

There are various causes for lipid abnormalities and various solutions including improving nutrition, exercise, medications and supplements.

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Shyness can be a person’s temperament – a trait one is born with, a biological trait. It can be modified by one’s experiences and choices and needs. The brain is born with certain biological predispositions – such as shyness. But it also reprograms and constantly restructures and modifies itself depending on the solutions it develops to the problems it experiences. For example, if one desires to modify one’s brain structure to modify the trait of shyness because of social pressure or shame (the emotion caused by one not meeting one’s own expectations or rules), then one will find a solution (e.g. taking public speaking classes, engaging in group therapy, etc.).

The brain will change as much as it can if it is forced to find a solution in order to survive. It can rewire itself to a certain extent in order to do so. It is like learning a language. If one was dropped into a foreign country, one will have to learn the language to a certain extent in order to survive (e.g. to get food, clothing, shelter, etc.) no matter how old one is. If one does not set the condition that change is necessary for survival then change may not be achieved because it is not the solution to a problem. Thus with shyness, if avoidance is an available solution, then one may not change. But if avoidance is not a possible solution, then one would be forced to change.

Provigil or an SSRI may either help OR worsen OR cause no change depending on the underlying biological conditions underlying a social disorder or leg shaking. Determining the underlying biological condition is important to help determine what direction one may go when doing an intervention.

@loopy107 2952 wrote:

Thanks for all the insightful information Dr Mariano. Just have another question.
Can Provigil with SSRI help with my issue of feeling emotionally flat since I can’t feel love emotions?

Provigil with an SSRI can either help or worsen or have no effect on a condition depending on the underlying biological factors. It is important to determine as many of the underlying factors as one can in order to determine the direction one will go with an intervention.

Emotional flatness in some people is a behavioral solution to some problems such as trauma. Thus, as a behavioral solution, it may be difficult to improve unless an alternative and equally effective solution can be found. For example, for trauma experiences, one will have to learn how to psychologically compartmentalize the trauma in order to be able to place it in the back of one’s mind so one can ignore it and move forward.

Love is a complex emotion that includes feelings and behavior. It involves including the loved one into one’s identify or sense of self. Thus one will care about the loved one’s well-being because the loved one is part of oneself. Without the identification, love is often difficult to feel or achieve. The behavioral component of love is often a learned nurturing behavior. Thus, without the developmental basis for it (e.g. childhood rearing, etc.), nurturing behavior may not have become learned. And the person would be incapable of loving someone.

There are affinity and nurturing circuits in the brain that are activated when one feels love. Neither Provigil nor an SSRI may usually activate these circuits. Sometimes, the opposite instead may occur.