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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. 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.
ESTRADIOL:
Different tests for estrogen will give you different levels of estradiol. The different protocols involved simply give different numbers. 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 and less costly.
IGF-1 is one indirect way of measuring growth hormone. IGF-1 is increased by growth hormone, testosterone, DHEA, dopamine, thyroid hormone, among other signals. It is 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. 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 8-12If 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 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.
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 if problems occur.
GLUCOSE:
From a behavioral point of view, the optimal range for Glucose is between 93-100. 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 also does signal processing.
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 produces the major hormone binding proteins which then influence hormone signaling. These binding proteins also prolong the signals – causing them to be slow-release signals.
The liver also monitors hormone status, such as the level of steroid hormones. When steroid hormone levels are low, the liver produces cholesterol from glucose. Cholesterol is the building block for the steroid hormones. Thus, a high cholesterol indicates one may have a hormone deficiency.
Vitamin D is a steroid hormone.
@DrMariano 198 wrote:
An optimum iron level as measured by Ferritin in men is about 150.
Excessive iron is dangerous. It is highly oxidizing. 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.
Hi Dr Mariano,
would you expect hemochromatosis to be a probable factor for little to no response to very high HRT doses, such as 5gr Armour, 40mg Cortisol, 1gm 10% Testosterone?
What do you consider as high Ferritin? Is it dependant on the persons frame?Cheers
@josh 848 wrote:
Hi Dr Mariano,
would you expect hemochromatosis to be a probable factor for little to no response to very high HRT doses, such as 5gr Armour, 40mg Cortisol, 1gm 10% Testosterone?
What do you consider as high Ferritin? Is it dependant on the persons frame?Cheers
Possibly. Hemochromatosis can cause tissue destruction.
When Ferritin goes over 200, one has to consider Hemochromatosis or other iron overload disorder as a possible contributing factor to a person’s problems. When it is over 300, these conditions should definitely be considered.
Here is a good site for more information:
@DrMariano 198 wrote:
DHEA:
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.
Do you think the ultrasensitive assay is always accurate?
I have taken 5 tests since starting TRT, 3 have come back <2 mid week.
Do you feel the other assays are invalid?
@chaos 891 wrote:
Do you think the ultrasensitive assay is always accurate?
I have taken 5 tests since starting TRT, 3 have come back <2 mid week.
Do you feel the other assays are invalid?
From Quest Diagnostic’s point of view, the Ultrsensitive Estrdiol is sensitive down to within 2 pg/mL (I would assume this means +- 2 pg/ml).
Thus the test is pretty accurate.
The other estrogen tests are valid. It depends on what one is looking for.
For tests, the question is not whether or not it is accurate, but whether or not the test gives you the answer to what your are looking for.
There is no test for every possible estrogen – there are numerous variants of estrogen – 4-hydroxy, 2-hydroxy, 16-hydroxy variants, estriol, estrone, estradiol, etc.
Since all the tests give different numbers for estradiol, since they are different tests, one has to choose one test to base one’s experience upon.
What I noticed is that the Ultrasensitive Estradiol appears to be a summation of various estrogens, not just Estradiol. They tends to have the similar mass. The test tends to give the highest level of estradiol measured. Thus, it can be looked upon as a useful overall measure of estrogen signaling, given Estradiol is the strongest of the estrogens. This is the primary reason I would use the Ultrasensitive Estradiol.
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Obviously, when one has a near zero level of estradiol, one would have to discuss this issue with one’s physician to determine what may be happening.
When several ultrasensitive estradiol tests are close to zero, then the test result is replicable. And something is occurring to cause that.
For example, in postmenopausal women with hypoadrenalism, a near zero level of estradiol is fairly common because both the ovaries and adrenal glands in this situation are not producing sufficient estrogen.
In men, the question would be how low is testosterone, and how much is there of aromatase to convert testosterone to estrogen, and how quickly is estrogen being destroyed?
I don’t do use the Ultra E2 test any more Dr. John pushed this test on many men saying it’s the best it is when the lab is not having problems with the Machine that does the test. To many men myself and Hardasnails were given bad results coming in at <2 so they stopped taking there Arimidex thinking they are way to low.
I have lost count how many men got messed up using this test going to high on there E2 levels thinking they were to low. And high E2 levels mess up ones Sex life and Thyroid.
When I got this result my Dr. called Quest labs the Tech. he knows and was told they are having problems with this new test. So we did both the Ultra and Sensitive test on the same blood draw. Then Ultra come back very low yet the Sensitive the old test #4021 with the range of 13 to 54 came back 38 pg/ml to high for me thanks to the bad results from the Ultra test.
Yet they are having problems with this test and still sending out bad results and charging for them. I called my BCBS and told them not to pay for them this was some time ago.
Quest labs called me about the bill and when I told them why they told me they were sorry this test is not working right. I asked if it dose not work why are you messing up all them men having them think they are to low and billing them for it. They told me last week they will be looking into this billing problem and sending money back. If they do this will be a first.
@TESTOCULES 911 wrote:
Dr. Mariano…could you please comment on optimal free and total testosterone lab numbers.
I generally don’t use Free Testosterone. It does not reflect Testosterone signaling very well. It is only a small part of the testosterone signal.
When doing testosterone replacement treatment, as long as Total Testosterone is at least 650, then any remaining problems are not due to testosterone. They are problems with the rest of the system. This level is half-way between the reference ranges of 300-1000 ng/dL for testosterone and is in line with the Endocrine Society’s basic guidelines for testosterone replacement therapy. Generally, I would not treat a person with testosterone if their total testosterone is over 500 ng/dL. I would look for problems in the rest of the system that are contributing to their illness.
Optimal Testosterone is anywhere between 650 to 1000 ng/dL.
I solved the problem completely I went over to lab corp because I never had an issue with any patient having to have to get test redrawn vs the numerous time Quest has made simple errors that have cost me countless hours playing phone tag to correct them. I like lab corp because they are quick turn around time and and have different test that quest does not even offer. I like their ranges a lot better with clear starting point and end point in the scales. This <2 stuff makes it hard to identify for people that are on adex on monitor. When results comes back <2 then they feel great and then dr says to reduce adex by 25% their symptoms get worse for no reason. This has happened to me several time for over 2 years resulting in a rollercoaster ride that would drain anyone physically and emotionally. This is why I decided to make the change to lab corp because patients that use a estrodial sensitive symptoms correspond to the correct range. The changes in adex are much easier to monitor and I feel comfortable knowing that there has not been any invalid readings in past 2 years. Having the ability to go completely paperless now for lab testing results makes things alot easier and more stream line. Pateints from quest can log on to see there test results. No longer am I being emailed or asked to for results. Hours of faxing and calling customer service is the thing of the past. With a simple click of the button I can have fax sent to any where at any time. I can also copy and paste lab test to patients which have been verified on modified HIPPA form for permission to email results.
@hardasnails1973 932 wrote:
I solved the problem completely I went over to lab corp because I never had an issue with any patient having to have to get test redrawn vs the numerous time Quest has made simple errors that have cost me countless hours playing phone tag to correct them. I like lab corp because they are quick turn around time and and have different test that quest does not even offer. I like their ranges a lot better with clear starting point and end point in the scales. This <2 stuff makes it hard to identify for people that are on adex on monitor. When results comes back <2 then they feel great and then dr says to reduce adex by 25% their symptoms get worse for no reason. This has happened to me several time for over 2 years resulting in a rollercoaster ride that would drain anyone physically and emotionally. This is why I decided to make the change to lab corp because patients that use a estrodial sensitive symptoms correspond to the correct range. The changes in adex are much easier to monitor and I feel comfortable knowing that there has not been any invalid readings in past 2 years. Having the ability to go completely paperless now for lab testing results makes things alot easier and more stream line. Pateints from quest can log on to see there test results. No longer am I being emailed or asked to for results. Hours of faxing and calling customer service is the thing of the past. With a simple click of the button I can have fax sent to any where at any time. I can also copy and paste lab test to patients which have been verified on modified HIPPA form for permission to email results.
Nice.
I like lab ranges which are hard – i.e. having specific numbers, and results that are specific numbers. When you have results that are ranges (<32 pg/ml is a range, not a number), then the result is actually murky.
I like Lab Corp too. They bought and fused with Esoterix – fantastic lab company, a few years ago. When they can’t do it, they send it out to Arup labs, one of the gold standard specialty labs.
But, and a big BUT, I prefer patients go to their insurance company’s contract lab. Often this is Quest in the U.S. since they are big and can give steep discounts to companies, such as Blue Cross.
Otherwise, a lab panel can cost more than $3500 for initial labs and some fraction of that for follow ups. That is a lot to ask of a patient to pay for out-of-pocket – particularly a middle class patient with on-going standing health insurance.
Since I have patients from other states and countries, standardizing on a single lab gets very difficult.
I will work with the data that I can get, that a patient can reasonably afford. The less data, the more difficult the choices. But then, that’s life.
In my community psychiatry work, I work with extremely poor patients. Some have no insurance at all. And some have no income at all. I have to depend on my clinical skills – the history and physical and collateral information – when there is not lab available. With some, I may be lucky to get a Ferritin level paid for. Iron is a tricky nutrient since it is hard to estimate from the history and physical exam, and deficiencies and excesses can have similar presentation, though excesses have more risk.
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Good Point Dr. M I like Quest labs just don’t like there Ultra. Estradiol test with the range of < = 29 this test does not work right I all I am saying is I went back the there Sensitive test with the range of 13 to 54 pg/ml been using this lab test for yrs. never had a problem with it. It was when they came out with the Ultra. test we had problems big problems.
The first time this test happened was when we sent in blood for the sensitive test Quest called my Dr. telling him of there new test the Ultra test. So when my labs came back it said at the time it said <29 so here I am trying to keep my levels at 15 pg/ml with a SHBG or 20 and had no idea where my levels were at. I posted about this at Dr. John's forum he came back saying this is the only test he feels is actuate. It was about the 4th lab test using the Ultra test that they started to show the true number. My last test was <10 saying I am to low so I stopped taking Arimidex. I started to get all the symptoms of High Estradiol even started to have panic attacks again. This is when we did both of the test Ultra. and Sensitive and found out the Ultra. test Quest was having problems with it.
Being an Engineer we feel if it works don’t fix it.
@pmgamer18 950 wrote:
Good Point Dr. M I like Quest labs just don’t like there Ultra. Estradiol test with the range of < = 29 this test does not work right I all I am saying is I went back the there Sensitive test with the range of 13 to 54 pg/ml been using this lab test for yrs. never had a problem with it. It was when they came out with the Ultra. test we had problems big problems.
The first time this test happened was when we sent in blood for the sensitive test Quest called my Dr. telling him of there new test the Ultra test. So when my labs came back it said at the time it said <29 so here I am trying to keep my levels at 15 pg/ml with a SHBG or 20 and had no idea where my levels were at. I posted about this at Dr. John's forum he came back saying this is the only test he feels is actuate. It was about the 4th lab test using the Ultra test that they started to show the true number. My last test was <10 saying I am to low so I stopped taking Arimidex. I started to get all the symptoms of High Estradiol even started to have panic attacks again. This is when we did both of the test Ultra. and Sensitive and found out the Ultra. test Quest was having problems with it.
Being an Engineer we feel if it works don’t fix it.
If Quest is showing a range as the result (such as < 29), this is NOT an ultrasensitive estradiol test.
Quest’s ultrasensitive estradiol is suppose to be sensitive to within 2 pg/ml – from their own manual.
Thus the only range that can be a result should be < 2 pg/ml. Any level above 2 pg/ml should be given as a single real value (such as 15, 20, or 29, etc.), not a range.
Thus, I would complain to Quest as to why their test is flawed if I got a result such as < 29. And I would want a refund and a retest using the real ultrasensitive test.
When the result is < 29, that was the regular sensitivity estradiol test, not the ultrasensitive test.
as far as thyroid, can one with a tsh above 2.0 supplement benefit from thyroid hormone? if total t4 and free t3 are at the bottom of the ranges you look for.
Try doing this taking your morning temps before getting out of bed. Read how to do this in this link.
http://drbate.com/Ref/thyroid.html
If your temps are low then read these links.
http://www.stopthethyroidmadness.com/
http://personal.lig.bellsouth.net/w/u/wurmstei/
I am a mod at this forum for Men’s Thyroid Problems.
http://forums.realthyroidhelp.com/viewforum.php?f=5
Before going on meds learn about treating this all you can before taking meds.
Phil
@Mebigusmall 1734 wrote:as far as thyroid, can one with a tsh above 2.0 supplement benefit from thyroid hormone? if total t4 and free t3 are at the bottom of the ranges you look for.
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