Could this be low E2?

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I don't know what to make of these results. I've got crazy high total and E2, with average free.

I think I can rule out my protocol having anything to do with my joint pain, so that's a positive. And like I had said, sexually I've been good, which was my whole reason for trt in the first place.

But like you said the other day, and many others have said, I think I am better off trying to get off the AI. I mean, my E2 was fine a few weeks ago and now it's 164. If I stick with AI's, I'm never going to get dialed in.

I've tried lower doses and more frequent dosing and no AI's before, and my free hardly ever reached 15. But since it's not high now anyway, I might as well try again.

post #3/4/5


Sit back and listen! (24:05-31:33)

Endocrine Grand Rounds Presentation



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Defy Medical TRT clinic doctor
Even though I was talking about the vaccine and trying to figure out if it or low E2 might be causing my joint pain, until you posted I didn't even consider that the vax may have affected my hormones. Who knows. I wouldn't be surpirsed.

I'm paying out of pocket for bloods except for when seeing the uro once every 4 months, and SHBG is a little pricey.

As far as protocol, I looked back more closely and most lab results were when I was on 180mg E7D and 6.25 exemestane E3.5D. The results stayed the same when I switched to current protocol, but maybe time took its toll. But it still doesn't make sense, because if anything, my E2 should be lower not higher. I'm splitting my dosage and taking the same amount of Exemestane, so higher E2 is super weird,
Just to clarify, do u mind just posting ur total mg’s per week for test and exemestane when ur E2 was in the 20’s, and when it came back at 164?

Did u use the same exact e2 test with the same lab when it came back in the 20’s as u did when it came back at 164?

Going from an E2 of mid 20’s to 164 just makes zero sense based on my understanding of the protocols u were using. My guess is that one of those lab results is a mistake. There’s just no way ur E2 could have jumped that drastically.
 
Just to clarify, do u mind just posting ur total mg’s per week for test and exemestane when ur E2 was in the 20’s, and when it came back at 164?

Did u use the same exact e2 test with the same lab when it came back in the 20’s as u did when it came back at 164?

Going from an E2 of mid 20’s to 164 just makes zero sense based on my understanding of the protocols u were using. My guess is that one of those lab results is a mistake. There’s just no way ur E2 could have jumped that drastically.
This was after about four weeks on the current protocol, and is the last test I got until the current one.
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One question about the FT assay I'm using. Is it simply giving me a less accurate reading than ED or ultra, or is it randomly inaccurate? What I mean is this - I've been assuming that even though the assay is not perfect, it is proportionately correct to itself one reading to the next, meaning I can compare them from week to week.

For instance if I'm at 18 one week and then at 24 two weeks later, I was assuming my FT did go up roughly 33% (give or take). That's why I kept using that assay for the time being.

If you're telling me that they are so inaccurate that my lower reading could've been actually higher than my higher reading, as if there is just no rhyme or reason to the results, then I definitely have been wasting my time and money.
The Endocrine Society position

Current methods for measuring free testosterone (fT) are technically challenging and not accurate. The widely used direct immunoassay and tracer analog techniques for measuring fT have been shown to be inaccurate. Equilibrium dialysis, the reference method against which other methods are compared, is labor-intensive and cumbersome, and therefore has had limited clinical adoption. Recently, Endocrine Society’s Expert Panel acknowledged the experimental problems in fT measurements and concluded that "...the calculation of free testosterone is the most useful estimate of free testosterone in plasma..." For this reason they advocate for indirect "calculator" based methods, where free testosterone can be computed from the total testosterone, SHBG, and albumin concentrations.

However, we have demonstrated that even the calculated fT values derived from the prevailing equations, based on linear law-of-mass action models or empiric equations, differ systematically from free testosterone measured by equilibrium dialysis by as much as 40%.
 
One question about the FT assay I'm using. Is it simply giving me a less accurate reading than ED or ultra, or is it randomly inaccurate? What I mean is this - I've been assuming that even though the assay is not perfect, it is proportionately correct to itself one reading to the next, meaning I can compare them from week to week.

For instance if I'm at 18 one week and then at 24 two weeks later, I was assuming my FT did go up roughly 33% (give or take). That's why I kept using that assay for the time being.

If you're telling me that they are so inaccurate that my lower reading could've been actually higher than my higher reading, as if there is just no rhyme or reason to the results, then I definitely have been wasting my time and money.


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One question about the FT assay I'm using. Is it simply giving me a less accurate reading than ED or ultra, or is it randomly inaccurate? What I mean is this - I've been assuming that even though the assay is not perfect, it is proportionately correct to itself one reading to the next, meaning I can compare them from week to week.

For instance if I'm at 18 one week and then at 24 two weeks later, I was assuming my FT did go up roughly 33% (give or take). That's why I kept using that assay for the time being.

If you're telling me that they are so inaccurate that my lower reading could've been actually higher than my higher reading, as if there is just no rhyme or reason to the results, then I definitely have been wasting my time and money.


Screenshot (15456).png

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One question about the FT assay I'm using. Is it simply giving me a less accurate reading than ED or ultra, or is it randomly inaccurate? What I mean is this - I've been assuming that even though the assay is not perfect, it is proportionately correct to itself one reading to the next, meaning I can compare them from week to week.

For instance if I'm at 18 one week and then at 24 two weeks later, I was assuming my FT did go up roughly 33% (give or take). That's why I kept using that assay for the time being.

If you're telling me that they are so inaccurate that my lower reading could've been actually higher than my higher reading, as if there is just no rhyme or reason to the results, then I definitely have been wasting my time and money.


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You can throw in Free Testosterone (New Programs)
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One question about the FT assay I'm using. Is it simply giving me a less accurate reading than ED or ultra, or is it randomly inaccurate? What I mean is this - I've been assuming that even though the assay is not perfect, it is proportionately correct to itself one reading to the next, meaning I can compare them from week to week.

For instance if I'm at 18 one week and then at 24 two weeks later, I was assuming my FT did go up roughly 33% (give or take). That's why I kept using that assay for the time being.

If you're telling me that they are so inaccurate that my lower reading could've been actually higher than my higher reading, as if there is just no rhyme or reason to the results, then I definitely have been wasting my time and money.


Screenshot (15478).png
 
One question about the FT assay I'm using. Is it simply giving me a less accurate reading than ED or ultra, or is it randomly inaccurate? What I mean is this - I've been assuming that even though the assay is not perfect, it is proportionately correct to itself one reading to the next, meaning I can compare them from week to week.

For instance if I'm at 18 one week and then at 24 two weeks later, I was assuming my FT did go up roughly 33% (give or take). That's why I kept using that assay for the time being.

If you're telling me that they are so inaccurate that my lower reading could've been actually higher than my higher reading, as if there is just no rhyme or reason to the results, then I definitely have been wasting my time and money.

Sum this S**T UP!

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Accurate, comparable, and reliable measurements are ESSENTIAL!
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For the time being stick to testing your FT using Equilibrium Dialysis or Ultrafiltration, especially in cases of ALTERED SHBG!

Forget using/relying upon the calculated methods in cases of altered SHBG until this S**TSHOW comes to an end which will be soon enough.

Hard to believe everyone is still babbling on about this that or the other when the results/data have not even come out for Phase II.


Phase II: Research and Commercialization of TruT Algorithm (Sep.15, 2014-May 31, 2022)

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Phase II: Research and Commercialization of TruT Algorithm for Free Testosterone


*In phase I studies, we demonstrated that the TruTTM algorithm provides accurate free T values that match those obtained using the equilibrium dialysis in healthy and hypogonadal men

*The phase I studies have led to the adoption of the TruTTM algorithm at several institutions

*The phase II program will continue the development of the TruTTM algorithm by validating it in common conditions characterized by altered SHBG concentrations, such as obesity and aging (AIM 1), in healthy women across the menstrual cycle, and in women with PCOS (Aim 2). We will generate population-based reference ranges for free T (Aim 3). Phase II also includes plans for the commercialization of the TruTTM algorithm using a HIPAA-compliant infrastructure for its clinical adoption

*The phase II program will provide validation of the TruTTM algorithm in the two most common clinical indications for free T measurement? men suspected of hypogonadism and altered SHBG levels, and women with hyperandrogenic disorders




If you want to use/rely on the calculated methods then go F**KING NUTS!

*Currently, the CDC is developing a harmonized method for free T based on calculated free T using REVISED FORMULAE. This may bring the measurement of free T to a referable standard in clinical laboratories and common reference intervals that all clinicians can use

Now, why the F**K would they go and do that!




post#19



*The binding of T to SHBG is complex, which results in many different methods that directly measure or calculate free T. Some of these methods do not measure the free fraction of T and some formulae may provide less accurate results [40]

*Recent evidence suggests that the law of mass action formula which is based on the assumption that two T molecules bind to two binding sites on the SHBG with similar binding affinity may be incorrect. And further argues that the binding of T to SHBG may be a multistep, dynamic process with complex allosteric characteristics [65]. Based on this new model, investigators used a new formula to calculate free T in younger men in the Framingham Heart Study and showed that the newly calculated values were similar to those measured by equilibrium dialysis. They further verified that the calculated free T values had clinical diagnostic validity using data from the European Male Aging Study

*Currently, the CDC is developing a harmonized method for free T based on calculated free T using revised formulae. This may bring the measurement of free T to a referable standard in clinical laboratories and common reference intervals that all clinicians can use

*Perhaps the newer formula for calculated free T validated in multiple laboratories [65], will become generally available, correlate with free T by equilibrium dialysis, and demonstrate improved correlation with clinical symptoms and therapeutic responsiveness. If all these prove to be true, then this formula to calculate free T may be a justified replacement for free T measurement by the equilibrium dialysis methodology




Phase II: Research and Commercialization of TruT Algorithm for Free Testosterone
Jasuja, Ravi

https://grantome.com/grant/NIH/R44-AG045011-02


The measurement of testosterone (T) levels is central to the diagnosis of androgen disorders, such as hypogonadism in men and polycystic ovary syndrome (PCOS) in women. Circulating T is bound with high affinity to sex hormone-binding globulin (SHBG) and with substantially lower affinity to albumin; only the free fraction is biologically active. Conditions that affect SHBG concentrations, such as aging and obesity, alter total but not free T concentrations; in these conditions, the determination of free T is necessary to obtain an accurate assessment of androgen status. The tracer analog method, the most widely used method for free T, has been shown to be inaccurate. The equilibrium dialysis method, considered the reference method, is technically difficult to implement and standardize, and is not available in most hospital laboratories, leading the Endocrine Society's Expert Panel to conclude that ?? the calculation of free testosterone is the most useful estimate of free testosterone in plasma?? Therefore, there is an unmet need for algorithms that provide accurate estimates of free T that match those derived from equilibrium dialysis. We have designed a novel and accurate TruTTM algorithm for the determination of free T, based on the characterization of testosterone's binding to SHBG using modern biophysical techniques. We have discovered that testosterone's binding to SHBG is a dynamic multistep process that includes allosteric interaction between the two binding sites on an SHBG dimer. Our computational framework incorporates the correct binding parameters derived experimentally in these studies, the non-linear dynamics in T: SHBG association, and allostery

In phase I studies, we demonstrated that the TruTTM algorithm provides accurate free T values that match those obtained using the equilibrium dialysis in healthy and hypogonadal men
. We have also shown that the binding parameters that have formed the basis of previous equations (e.g., Vermeulen) are incorrect, and that free T values derived using these equations deviate substantially from free T measured by equilibrium dialysis. The phase I studies have led to the adoption of the TruTTM algorithm at several institutions.

The phase II program will continue the development of the TruTTM algorithm by validating it in common conditions characterized by altered SHBG concentrations, such as obesity and aging (AIM 1), in healthy women across the menstrual cycle, and in women with PCOS (Aim 2).
We will generate population-based reference ranges for free T (Aim 3). Phase II also includes plans for the commercialization of the TruTTM algorithm using a HIPAA-compliant infrastructure for its clinical adoption

The phase II program will provide validation of the TruTTM algorithm in the two most common clinical indications for free T measurement? men suspected of hypogonadism and altered SHBG levels, and women with hyperandrogenic disorders. It will also enable the development of a HIPAA-compliant platform that can be embedded into the electronic medical record for wider clinical adoption and for improving clinical care
 
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I didn't think to mention this, but there were two significant changes during the lead up to the last lab results. I can't find anything online that suggests either should've affected my E2, but maybe someone here knows something different. One is that I started taking adderall, 10mg daily. The other is that I started consuming high amounts of fiber. I basically went from zero fiber to high fiber. I also may have increased my caffeine consumption, but I'm not sure. I go back and forth using caffeine, and I can't remember if I was using it much at the time of the prior results.

Just in case he checks - I'm not ignoring madman's suggestion. I need to see my uro in August, He's going to test me the standard way, and I'm not going to ask him for anything else. He just wouldn't understand. But I will schedule a lab visit for hopefully that same day and get the gold standard tests. Then I can compare them to each other.
 
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