Some pointers from answering a recent post.
DHEA:
DHEA is important – but in the hierarchy of signals in the body, there are more important signals to consider improving first since otherwise DHEA is a minor player in a person’s overall health. For example, in men, the following hormones are more important to address: thyroid, cortisol. If DHEA is greater than 200, I would address the other issues first.
DHEA can go to estrone rather than testosterone or estradiol. Thus if DHEA levels are difficult to increase, then aside from elimination issues and absorption issues as previously discussed, the metabolism of DHEA is important to consider. If one has an overly active enzyme pathway that leads to DHEA being converted to Estrone, then one has a significant problem. Estrone is a pro-carcinogenic / pro-cancer estrogen. Taking DIM or iodine may help convert this to less carcinogenic estrogens, but then one will have to closely monitor this over time, reducing DHEA supplementation if necessary to avoid the conversion to estrone. Addressing the overall impairment in adrenal function to help improve natural production of DHEA may be a better idea than adding more exogenous DHEA. In an older man, where the DHEA producing layer of the adrenal gland has thinned out due to aging, some DHEA supplementation may be necessary – so long as estrone production is minimized. This is why I may settle for a lower level of DHEA – not severely low, but a “good enough” level – rather than risk excessive estrone.
ESTRADIOL:
Different tests for estrogen will give you different levels of estradiol. The different protocols involved simply give different numbers. If a person is obsessive-compulsive or rule-bound, all of the different results would drive that person nuts. Given this scenario, one has to CHOOSE ONE of the tests and base their clinical decisions on the observations and experience with that one test. It is one’s experience and observations, then, that would help determine the interpretation.
For myself, I have found that the ultrasensitive estradiol is the most clinically useful test for estrogen signaling activity. This means whether or not estrogen is too high or too low in relationship to the other hormones, neurotransmitters, and other signals. This is particularly important for signals which are directly affected by estrogen: testosterone, thyroid hormone, serotonin, dopamine, norepinephrine.
The fractionated estrogens test is useful for determining possibly what is happening to estrogens or in the case of DHEA, where it is going. But a 24-hour urine hormone test – where many hormones and their metabolites are measured (such as done by Meridian Labs or Rhein labs) would tell you more about the pathways involved.
GROWTH HORMONE:
Growth hormone is generally the last hormone to optimize. This is because it potentially affects many of the other hormones negatively (such as thyroid and the adrenal hormones), causing more problems and complicating the clinical picture if it is added first. Additionally, and possibly more importantly, if one addresses the other hormones and neurotransmitters first, then the dose of growth hormone needed to improve function is LOWER. This can then save a person a lot of money in the treatment.
IGF-1 is one indirect way of measuring growth hormone. A 24-hour urine growth hormone can also be done but IGF-1 is the most frequently used test. IGF-1 is increased by growth hormone, testosterone, DHEA, dopamine, thyroid hormone, among other signals. It is multiply-determined and is thus not purely determined by growth hormone. However, IGF-1 does the bulk of the work for growth hormone and is thus a valid measure of its activity.
At what level of IGF-1 indicates growth hormone deficiency (the only legal indication for growth hormone treatment) is actually subjective. Anti-aging doctors, who want to optimize growth hormone levels, tend to use 250 as the lower end of the reference range for IGF-1. Some doctors use a lower level. Many won’t treat unless it is definitely below the lower reference range. For myself, 250 is a bit on the high end for a lower reference range. If it is closer to 150, I would consider growth hormone treatment.
Growth hormone can improve a person’s sense of well-being when used well. Improved mood, libido, energy can occur – once the other hormone and neurotransmitters are optimized. However, it may not prolong life. It may actually limit one’s lifespan to about the 90s rather than letting one live past 100. Thus one has to assess whether one chooses to live well or live longer.
THYROID HORMONE:
A useful target if considering primarily lab tests for optimizing thyroid hormone is the following:
TSH <= 1.0 Free T3 between 3.3 to 3.9 Total T4 between 8-12
If at least one lab test is below these ranges, then a person may exhibit signs of hypothyroidism.
T4 levels are important since the brain does its own conversion of T4 to T3. The brain compartment can have different T4 and T3 levels than the rest of the body. The brain and body are in two different compartments, separated by the blood brain barrier. In Alzheimer's disease, brain thyroid levels are lower than the rest of the body.
TSH is not as important a measurement compared to measuring Free T3 and Total T4. If a person has some metabolic problem - including having heart disease, diabetes, low iron, etc. then the nervous system cannot function well and TSH will be abnormally low since the brain will have difficulty monitoring thyroid hormone and making TSH.
FERRITIN:
Ferritin is the most important measure of iron. Iron in the body is mostly in hemoglobin and myoglobin. However, iron is also used by every single cell in the body as part of many enzymes. Many of the enzymes which participate in the citric acid cycle to generate ATP - the basic energy storage unit in the body - in mitochondria have iron in their structure. Ferritin gives one an idea of how much iron is available to the rest of the body's cells for metabolic purposes.
Without iron, cells are significantly impaired in metabolic activity. They can't make enough ATP to do their activities. Thus, optimizing hormone, neurotransmitters and other signals doesn't work very well since they are only signals. They are signals to trigger cellular activities. But these activities cannot be done without ATP.
An optimum iron level as measured by Ferritin in men is about 150. In women, it is about 100-120. These are mid-range values. A ferritin of 75, in one study, was found to be the lower end of normal for senior citizens. They can be even develop iron-deficiency anemia at that level of iron.
Excessive iron is dangerous. It is highly oxidizing. It will also trap nitric oxide - used among other things to reduce blood pressure and improve blood flow. It is destructive to tissues - causing cell death in the testes, ovaries, thyroid gland, liver, brain, etc. In testing Ferritin, I have surprisingly found a large number of patients, who have been treatment resistant, to have hemochromocytosis - a disease of excessive iron storage. It usually occurs in about 1 in 200-400 Caucasian men.
CORTISOL:
Outside of Addison's disease, where there is actual destruction of the adrenal glands, low cortisol and adrenal cortex output may occur from stress-related conditions. This has been called "Adrenal Fatigue". However, in retrospect, I don't think this is a good term in that it implies something is wrong structurally with the adrenals - a bone of contention and misunderstanding. A better term is hypothalamic-pituitary-adrenal axis dysregulation (HPA dysregulation, for short). Then the problem may lie anywhere from the nervous system, endocrine system, immune system, metabolism and nutrition, etc. Posttraumatic stress disorder is an example where there is hypothalamic-pituitary-adrenal axis dysregulation, resulting in low cortisol. Frequently, in PTSD, I find cortisol levels around 6 and below. When I see such levels, I would inquire about a person's traumatic experiences.
Cortisol treatment may help. The problem is that Cortisol treatment also slows down the output of the adrenal cortex - including DHEA, Pregnenolone, Progesterone, Testosterone, Estradiol, etc. These other signals also are important. They also can regulate mood. Thus in some people, it is not enough to add cortisol. It is also important to optimize the other adrenal hormones/signals to avoid causing mood dysregulation and other problems with a cortisol-alone treatment.
Improving sleep is a huge help in improving adrenal cortex function.
PREGNENOLONE:
Pregnenolone is the most produced neurotransmitter in the brain. It is important for memory and attention. DHEA is the second most produced neurotransmitter in the brain. Pregnenolone is also produced by the adrenal glands. Pregnenolone treatment is a drop in the ocean when addressing low pregnenolone levels. Thus I don't expect levels to improve. But enough exogenous pregnenolone can improve memory and mood when at least some gets into the brain. It can also be metabolized to the other steroid hormones. Thus these may have to be monitored. In the experience of Thierry Hertoghe, MD, a colleague, and considered Europe's best anti-aging doctor (though I told him he should have stayed a psychiatrist), Pregnenolone is safe to use up to a dose of around 200 mg a day. But in a few people, its metabolites will need to examine. Jonathan Wright, MD, for example, told me of a couple of men who had problems gaining muscle mass when exercising, who he found to have increased estrogens from pregnenolone, as a problem.
GLUCOSE:
From a behavioral point of view, the optimal range for Glucose is between 93-100. Thus a person with a glucose below 93 I would consider hypoglycemic from a behavioral/brain function point of view. They would have problems with gluconeogenesis or glycogenolysis usually secondary to impaired cortisol or thyroid hormone production, though metabolic issues such as low iron problems may cause this as well.
CHOLESTEROL:
The liver is the major signal ender for the long-distance fluid-transmitted signals in the body - e.g. the hormones. A signal needs to be ended as well as transmitted. The liver's enzymes degrade hormonal signals.
The liver also does signal processing.
The liver produces the major hormone binding proteins (e.g. thyroid binding globulin, etc.) which then influence hormone signaling. These binding proteins also prolong the signals - causing them to be slow-release signals. For example, without sex hormone binding globulin, testosterone's half-life will be reduced to 10-100 minutes.
The liver also monitors hormone status. It monitors steroid hormone levels, for example. When steroid hormone levels are low, the liver produces cholesterol from glucose. Cholesterol is the building block for the steroid hormones. Thus, outside of a genetic disease which causes excessive cholesterol production, a high cholesterol level indicates one has a hormone deficiency.
VITAMIN D:
Vitamin D is a steroid hormone.
DHEA:
DHEA is important – but in the hierarchy of signals in the body, there are more important signals to consider improving first since otherwise DHEA is a minor player in a person’s overall health. For example, in men, the following hormones are more important to address: thyroid, cortisol. If DHEA is greater than 200, I would address the other issues first.
DHEA can go to estrone rather than testosterone or estradiol. Thus if DHEA levels are difficult to increase, then aside from elimination issues and absorption issues as previously discussed, the metabolism of DHEA is important to consider. If one has an overly active enzyme pathway that leads to DHEA being converted to Estrone, then one has a significant problem. Estrone is a pro-carcinogenic / pro-cancer estrogen. Taking DIM or iodine may help convert this to less carcinogenic estrogens, but then one will have to closely monitor this over time, reducing DHEA supplementation if necessary to avoid the conversion to estrone. Addressing the overall impairment in adrenal function to help improve natural production of DHEA may be a better idea than adding more exogenous DHEA. In an older man, where the DHEA producing layer of the adrenal gland has thinned out due to aging, some DHEA supplementation may be necessary – so long as estrone production is minimized. This is why I may settle for a lower level of DHEA – not severely low, but a “good enough” level – rather than risk excessive estrone.
ESTRADIOL:
Different tests for estrogen will give you different levels of estradiol. The different protocols involved simply give different numbers. If a person is obsessive-compulsive or rule-bound, all of the different results would drive that person nuts. Given this scenario, one has to CHOOSE ONE of the tests and base their clinical decisions on the observations and experience with that one test. It is one’s experience and observations, then, that would help determine the interpretation.
For myself, I have found that the ultrasensitive estradiol is the most clinically useful test for estrogen signaling activity. This means whether or not estrogen is too high or too low in relationship to the other hormones, neurotransmitters, and other signals. This is particularly important for signals which are directly affected by estrogen: testosterone, thyroid hormone, serotonin, dopamine, norepinephrine.
The fractionated estrogens test is useful for determining possibly what is happening to estrogens or in the case of DHEA, where it is going. But a 24-hour urine hormone test – where many hormones and their metabolites are measured (such as done by Meridian Labs or Rhein labs) would tell you more about the pathways involved.
GROWTH HORMONE:
Growth hormone is generally the last hormone to optimize. This is because it potentially affects many of the other hormones negatively (such as thyroid and the adrenal hormones), causing more problems and complicating the clinical picture if it is added first. Additionally, and possibly more importantly, if one addresses the other hormones and neurotransmitters first, then the dose of growth hormone needed to improve function is LOWER. This can then save a person a lot of money in the treatment.
IGF-1 is one indirect way of measuring growth hormone. A 24-hour urine growth hormone can also be done but IGF-1 is the most frequently used test. IGF-1 is increased by growth hormone, testosterone, DHEA, dopamine, thyroid hormone, among other signals. It is multiply-determined and is thus not purely determined by growth hormone. However, IGF-1 does the bulk of the work for growth hormone and is thus a valid measure of its activity.
At what level of IGF-1 indicates growth hormone deficiency (the only legal indication for growth hormone treatment) is actually subjective. Anti-aging doctors, who want to optimize growth hormone levels, tend to use 250 as the lower end of the reference range for IGF-1. Some doctors use a lower level. Many won’t treat unless it is definitely below the lower reference range. For myself, 250 is a bit on the high end for a lower reference range. If it is closer to 150, I would consider growth hormone treatment.
Growth hormone can improve a person’s sense of well-being when used well. Improved mood, libido, energy can occur – once the other hormone and neurotransmitters are optimized. However, it may not prolong life. It may actually limit one’s lifespan to about the 90s rather than letting one live past 100. Thus one has to assess whether one chooses to live well or live longer.
THYROID HORMONE:
A useful target if considering primarily lab tests for optimizing thyroid hormone is the following:
TSH <= 1.0
Free T3 between 3.3 to 3.9
Total T4 between 8-12
If at least one lab test is below these ranges, then a person may exhibit signs of hypothyroidism.
T4 levels are important since the brain does its own conversion of T4 to T3. The brain compartment can have different T4 and T3 levels than the rest of the body. The brain and body are in two different compartments, separated by the blood brain barrier. In Alzheimer's disease, brain thyroid levels are lower than the rest of the body.
TSH is not as important a measurement compared to measuring Free T3 and Total T4. If a person has some metabolic problem - including having heart disease, diabetes, low iron, etc. then the nervous system cannot function well and TSH will be abnormally low since the brain will have difficulty monitoring thyroid hormone and making TSH.
FERRITIN:
Ferritin is the most important measure of iron. Iron in the body is mostly in hemoglobin and myoglobin. However, iron is also used by every single cell in the body as part of many enzymes. Many of the enzymes which participate in the citric acid cycle to generate ATP - the basic energy storage unit in the body - in mitochondria have iron in their structure. Ferritin gives one an idea of how much iron is available to the rest of the body's cells for metabolic purposes.
Without iron, cells are significantly impaired in metabolic activity. They can't make enough ATP to do their activities. Thus, optimizing hormone, neurotransmitters and other signals doesn't work very well since they are only signals. They are signals to trigger cellular activities. But these activities cannot be done without ATP.
An optimum iron level as measured by Ferritin in men is about 150. In women, it is about 100-120. These are mid-range values. A ferritin of 75, in one study, was found to be the lower end of normal for senior citizens. They can be even develop iron-deficiency anemia at that level of iron.
Excessive iron is dangerous. It is highly oxidizing. It will also trap nitric oxide - used among other things to reduce blood pressure and improve blood flow. It is destructive to tissues - causing cell death in the testes, ovaries, thyroid gland, liver, brain, etc. In testing Ferritin, I have surprisingly found a large number of patients, who have been treatment resistant, to have hemochromocytosis - a disease of excessive iron storage. It usually occurs in about 1 in 200-400 Caucasian men.
CORTISOL:
Outside of Addison's disease, where there is actual destruction of the adrenal glands, low cortisol and adrenal cortex output may occur from stress-related conditions. This has been called "Adrenal Fatigue". However, in retrospect, I don't think this is a good term in that it implies something is wrong structurally with the adrenals - a bone of contention and misunderstanding. A better term is hypothalamic-pituitary-adrenal axis dysregulation (HPA dysregulation, for short). Then the problem may lie anywhere from the nervous system, endocrine system, immune system, metabolism and nutrition, etc. Posttraumatic stress disorder is an example where there is hypothalamic-pituitary-adrenal axis dysregulation, resulting in low cortisol. Frequently, in PTSD, I find cortisol levels around 6 and below. When I see such levels, I would inquire about a person's traumatic experiences.
Cortisol treatment may help. The problem is that Cortisol treatment also slows down the output of the adrenal cortex - including DHEA, Pregnenolone, Progesterone, Testosterone, Estradiol, etc. These other signals also are important. They also can regulate mood. Thus in some people, it is not enough to add cortisol. It is also important to optimize the other adrenal hormones/signals to avoid causing mood dysregulation and other problems with a cortisol-alone treatment.
Improving sleep is a huge help in improving adrenal cortex function.
PREGNENOLONE:
Pregnenolone is the most produced neurotransmitter in the brain. It is important for memory and attention. DHEA is the second most produced neurotransmitter in the brain. Pregnenolone is also produced by the adrenal glands. Pregnenolone treatment is a drop in the ocean when addressing low pregnenolone levels. Thus I don't expect levels to improve. But enough exogenous pregnenolone can improve memory and mood when at least some gets into the brain. It can also be metabolized to the other steroid hormones. Thus these may have to be monitored. In the experience of Thierry Hertoghe, MD, a colleague, and considered Europe's best anti-aging doctor (though I told him he should have stayed a psychiatrist), Pregnenolone is safe to use up to a dose of around 200 mg a day. But in a few people, its metabolites will need to examine. Jonathan Wright, MD, for example, told me of a couple of men who had problems gaining muscle mass when exercising, who he found to have increased estrogens from pregnenolone, as a problem.
GLUCOSE:
From a behavioral point of view, the optimal range for Glucose is between 93-100. Thus a person with a glucose below 93 I would consider hypoglycemic from a behavioral/brain function point of view. They would have problems with gluconeogenesis or glycogenolysis usually secondary to impaired cortisol or thyroid hormone production, though metabolic issues such as low iron problems may cause this as well.
CHOLESTEROL:
The liver is the major signal ender for the long-distance fluid-transmitted signals in the body - e.g. the hormones. A signal needs to be ended as well as transmitted. The liver's enzymes degrade hormonal signals.
The liver also does signal processing.
The liver produces the major hormone binding proteins (e.g. thyroid binding globulin, etc.) which then influence hormone signaling. These binding proteins also prolong the signals - causing them to be slow-release signals. For example, without sex hormone binding globulin, testosterone's half-life will be reduced to 10-100 minutes.
The liver also monitors hormone status. It monitors steroid hormone levels, for example. When steroid hormone levels are low, the liver produces cholesterol from glucose. Cholesterol is the building block for the steroid hormones. Thus, outside of a genetic disease which causes excessive cholesterol production, a high cholesterol level indicates one has a hormone deficiency.
VITAMIN D:
Vitamin D is a steroid hormone.
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