How does this even happen?

[Mitch]

All lab work done at labcorp..

February my estrodiol was at 8.5 (8-35) range while injection 50mg 2x a week and taking .25 anastrozle.. So I eliminated the AI and and kept injections the same, e2 went up to 28.. decided to go EOD injections of 25mg and added DIM around then.. Just got labs back from that protocol because I felt something was off and figured it was high E2... labs told me new protocol brought by E2 down to 5.5 (8-35 range)... how did I crash my e2 without an AI? Is that possible? What should I do next?? Test is at 767 and my shgb is usually around 39-40 (range of 16-50)

 

[Systemlord]

Are we doing labs at the appropriate intervals every 6 weeks after a making changes to our TRT protocol?

 

[Mitch]

Are we doing labs at the appropriate intervals every 6 weeks after a making changes to our TRT protocol?

Yes this was 6 weeks from April labs... My doctor didn’t want to see me until 3 months after last appt.. I pulled e2 sensitive and tt and ft labs on my own because I felt off..

 

[Systemlord]

Yes this was 6 weeks from April labs... My doctor didn’t want to see me until 3 months after last appt.. I pulled e2 sensitive and tt and ft labs on my own because I felt off..

If these labs are accurate, it would mean frequent injections lowers E2 and you need large injections to have adequate E2 levels. It could also mean you just lack the aromatase enzymes needed for T->E2 conversion.

You also never mentioned Free T which is another part of the equation.

 

[Mitch]

If these labs are accurate, it would mean frequent injections lowers E2 and you need large injections to have adequate E2 levels. It could also mean you just lack the aromatase enzymes needed for T->E2 conversion.

You also never mentioned Free T which is another part of the equation.

Planning on going back to 2x a week at 50-60mg 2x a week.. cutting the dim and seeing where I am at in 6 weeks.

Free t 10.7 (8.7-21.5)

 

[Systemlord]

Free t 10.7 (8.7-21.5)

We see this in high SHBG men, Total T is high and Free T and E2 are both low. Your SHBG binds androgens strongly, you need more Total T to increase Free T to high normal, then we shall see estrogen increase.

60mg twice weekly may not be enough if 50mg twice weekly had you at a similar Free T level, you may need Total T >1000.

 

[madman]

Planning on going back to 2x a week at 50-60mg 2x a week.. cutting the dim and seeing where I am at in 6 weeks.

Free t 10.7 (8.7-21.5)

Your FT is by no means low simply because you had the wrong testing done as the direct immunoassay is inaccurate and waste of money as far as I am concerned!

Almost everyone uses/relies on the the direct immunoassay for FT testing when in fact they would be hard pressed to find out that their FT levels are a lot higher when they use the more accurate testing method such as the gold standard Equilibrium Dialysis or Ultrafiltration or use the newer calculated TruT.

If you want to know where your FT levels truly sit than you would need to get the gold standard Equilibrium Dialysis or Ultrafiltration or better yet save yourself the money and use the newer calculated method TruT Free Testosterone Calculator by FPT







Current problems with accurate free testosterone determination
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. As an alternative, free testosterone can be computed from the total testosterone, SHBG, and albumin concentrations. 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...​

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%.




Improved TruT Companion Diagnostics
Based on the fundamental discovery of testosterone partitioning, our team has developed an accurate free testosterone determination method. While examining the mechanistic origin of this systematic inaccuracy in free testosterone values using the linear model of SHBG:testosterone association, we discovered that the SHBG dimer exhibits conformational allostery in binding testosterone. Our TruT™ companion diagnostic, incorporating the correct parameters and non-linear dynamics in T:SHBG association has resulted in a framework for accurate determination of free testosterone values.

The TruT algorithm improves the accuracy of fT calculations, reducing the potential for misdiagnosis, and better informing providers when designing treatments.




Our patent protected, novel TruT™ companion diagnostic framework provides accurate determination of free testosterone concentrations. This algorithm is based on experimental data demonstrating that testosterone’s binding to SHBG is a multi-step process involving an allosteric interaction between the two binding sites on the SHBG dimer. Estimates of free testosterone derived incorporating the allosteric coupling of SHBG monomers within the dimer provide accurate determination of free testosterone without systematic deviation from values obtained using equilibrium dialysis.




If we take your TT 767 ng/dL, SHBG 40 nmol/L (by no means that high) and Albumin 4.3 g/dL (mean) than your FT is 25.88 ng/dL (just above mid-range (mean) of the reference range 16-31 ng/dL)

Can you increase your TT to bring up your FT levels.....absolutely but you will in no way need the extreme levels of TT most would think!


TT 900 ng/dL, SHBG 40 nmol/L and Albumin 4.3 ng/dL (mean) than FT is 30.99 ng/dL (top of the reference range 16-31 ng/dL)

A TT of 900 ng/dL would put your FT levels at 30.99 ng/dL.....right at the top of the reference range 16-31 ng/dL.


So much for the 1000+ TT

 

[madman]

We see this in high SHBG men, Total T is high and Free T and E2 are both low. Your SHBG binds androgens strongly, you need more Total T to increase Free T to high normal, then we shall see estrogen increase.

60mg twice weekly may not be enough if 50mg twice weekly had you at a similar Free T level, you may need Total T >1000.

Still caught up on this direct immunoassay thing?


Until you understand the complete picture of T:SHBG association.....you will remain lost!



As you should be well aware this paper was posted last year!
A Reappraisal of Testosterone’s Binding in Circulation: Physiological and Clinical Implications


SHBG
The distribution of SHBG-bound testosterone differs in men and women: In the presence of estradiol, about 20% of binding sites are occupied by testosterone (11). The reported association constant for binding of testosterone to SHBG has varied among published studies depending on the experimental conditions, but it is consistently reported to be around 1 × 109 L/mol with two binding sites on each SHBG homodimer (4, 5, 28–31). Known variants, including the rs6258, rs143521188, rs143269613, rs146779355, and rs373769356 polymorphisms, decrease affinity for testosterone and higher equilibrium dissociation constant (Kd) values (32, 33). Notably, previous binding studies have assumed that the two binding sites on the SHBG homodimer are equivalent. A recent reappraisal of testosterone binding to SHBG using modern biophysical techniques indicated that the two binding sites on the SHBG dimer are not equivalent and that there is an allosteric interaction between the binding sites on the SHBG dimer such that the second testosterone molecule binds SHBG with a substantially different affinity than the first binding site (34). The allosteric model of the multistep binding of testosterone to SHBG is discussed later in this review.



*read this over and over until you truly see the significance of this.


Known variants, including the rs6258, rs143521188, rs143269613, rs146779355, and rs373769356 polymorphisms, decrease affinity for testosterone and higher equilibrium dissociation constant (Kd) values (32, 33).





Notably, previous binding studies have assumed that the two binding sites on the SHBG homodimer are equivalent. A recent reappraisal of testosterone binding to SHBG using modern biophysical techniques indicated that the two binding sites on the SHBG dimer are not equivalent and that there is an allosteric interaction between the binding sites on the SHBG dimer such that the second testosterone molecule binds SHBG with a substantially different affinity than the first binding site (34).

 

[Vince Carter]

I don't think given your SHBG that EOD was warranted, worthwhile to try but it seems as far as the numbers go you did better on E3.5D

 

[Mitch]

I don't think given your SHBG that EOD was warranted.

Obviously, I just didn’t think it would tank my E2 with Dim... just trying to keep E2 under control without AI. Going back to 50mg 2x a week. Also, may stop by labcorp and run the e2 again just to confirm the results, because I am so surprised. Going eod dropped my e2 by 21

 

[Vince Carter]

DIM will not lower your E, not in any way. What DIM can help with is symptoms. You're drop in E could be anything else but it's not DIM, I'd point more to the lab mistake.

 

[Mitch]

DIM will not lower your E, not in any way. What DIM can help with is symptoms. You're drop in E could be anything else but it's not DIM, I'd point more to the lab mistake.

Got my lab request through discounted labs, will run e2 again today. What other factors could make this happen? Anything else I should run labs for?

 

[fifty]

E2 sensitive test has a higher rate of failure than eclia. I am almost to the point where I’ll just test regular estradiol ($20) which is less likely to be a total fail with a turnaround time of 1 day rather than 4-5days with the sensitive test.

Just know that e2 sensitive will almost always be lower than the regular estradiol test.

Everyone espouses e2 lcms...while they’re at the same time running the non-lcms cheap total T and direct free T...going on trt when their direct free T comes back 9. I think that’s a bigger problem.

 

[Vince Carter]

Labs seem to be an increasingly challenging thing, I just had a set that was a little odd, from what I expected.

 

[Mitch]

Labs seem to be an increasingly challenging thing, I just had a set that was a little odd, from what I expected.

So, I was thinking for sure high E2, even took a 1/4 tab of AI last two injections (I know, I know, wait for labs) this morning I feel great and had morning wood.

 

[fifty]

So your labs said 5 and you took an ai instead of waiting a week...

 

[Mitch]

So your labs said 5 and you took an ai instead of waiting a week...

No took AI after labs before getting results... I have read a hundred times wait for labs, but was desperate to feel better and may have now may have it made worse.. I have yet to find any thing that talks about crashing estrodiol without using an AI.. I even consulted my doc, who instructed me to cut T dose and take an AI and said labs weren’t necessary.. I ran them on my own anyways

 

[Mitch]

Confirmed.... low level of E2 on labcorp sensitive test. I ran it again an I was at a 4 (8-35 range) this was with a EOD injection and DIM protocol. No AI.. So, now I changed my protocol to no DIM and every 3.5 day injections and will see how labs look in 6 weeks... Glad I didn’t listen to my doc who thought my e2 must have been high and take ai’s without labs...

 

[Mitch]

DIM will not lower your E, not in any way. What DIM can help with is symptoms. You're drop in E could be anything else but it's not DIM, I'd point more to the lab mistake.

Eod and Dim were the only things i was doing to control E2... Labs confirmed it was low E2.... Now I guess I just have to wait it out.. I did find some other guys on forums who have said DIM crashed them too... I always thought DIM just controlled the radicals... with your vast knowledge and can you think of any other reason it would crash like it did?

 

[Vince Carter]

That's just my belief, DIM deals with symptoms but isn't an AI but hey lots of guys can be a real surprise in how they respond to this or that which might be unconventional. A removal of the DIM and a retest will tell the tale if you pursued that.