High Total T, low free T, high E2 - feel like utter shit

[bagelmatic]

Just a short intro:
i've been feeling like utter shit for about 2 years now and i think i suffered from low T and high E during my puberty but about 18 months ago i started eating very healthily and consistently working out about 6 days a week on a PPL routine with cardio.
Despite this i still find it really hard to put on muscle and lose fat and my body composition/body fat deposition would look very 'Skinny fat'
Other things i've been facing for about a year or more
-Loss of libido [gotten alot worse over the past few months to the point where it's hard to even get erections sometimes, and NO morning wood at all ever]
-Alot of brain fog
-Constant low level to medium level depression
-Gynocomastia i got during puberty seemingly feeling worse

I've done 5 blood tests over the course of 2 years and here's the bloodwork of the last one:

The previous blood test was as followed:

In all of the blood tests i've done the recurring theme has been
-High estrogen ranging from 120-179
-Lower range free T
-High SHBG [ranging from 50-90]


I've tried Calcium D glucarate alongside DIM to control the estrogen and it went down from 179 to 120 after 6 weeks of that protocol, but my free T went down from 0.406 nmol/l to 0.29 nmol/l.
I've tried Boron to lower the SHBG and it doesn't really make much of a difference

 

[Sean Mosher]

Can we ask how old you are?
With that level of SHBG most of your T is definitely bound up and your freeT level shows that.
Should you be a candidate for therapy you would definitely need a decent dose to come over the top of that SHBG and allow your FreeT to climb.
Would like to see a little more background and possibly thyroid numbers as well.

 

[Systemlord]

Your elevated SHBG is definitely affecting Free T negatively, thyroid labs look underwhelming, Free T3 is on the lower end.

You seem to be holding onto your Free T4 and are not converting it properly to Free T3, this is why Free T3 is low and you definitely have a conversion problem.

You more than likely need T3 only thyroid treatment, otherwise free thyroid hormones will shift hard over to Free T4 and Free T3 will still be low in relation to Free T4.

Curious where Reverse T3 sits.

 

[bagelmatic]

Thanks for the replies so far guys @Systemlord @Sean Mosher
To answer your questions
-i'm 26 years old
here's more information about my thyroid

I've gone to two private endocrinologists and they were reluctant to put me on thyroid medication and we tried diet changes/supplement changes but nothing really worked

 

[madman]

Just a short intro:
i've been feeling like utter shit for about 2 years now and i think i suffered from low T and high E during my puberty but about 18 months ago i started eating very healthily and consistently working out about 6 days a week on a PPL routine with cardio.
Despite this i still find it really hard to put on muscle and lose fat and my body composition/body fat deposition would look very 'Skinny fat'
Other things i've been facing for about a year or more
-Loss of libido [gotten alot worse over the past few months to the point where it's hard to even get erections sometimes, and NO morning wood at all ever]
-Alot of brain fog
-Constant low level to medium level depression
-Gynocomastia i got during puberty seemingly feeling worse

I've done 5 blood tests over the course of 2 years and here's the bloodwork of the last one:
View attachment 7749
View attachment 7750
View attachment 7751


The previous blood test was as followed:
View attachment 7752
View attachment 7753


In all of the blood tests i've done the recurring theme has been
-High estrogen ranging from 120-179
-Lower range free T
-High SHBG [ranging from 50-90]


I've tried Calcium D glucarate alongside DIM to control the estrogen and it went down from 179 to 120 after 6 weeks of that protocol, but my free T went down from 0.406 nmol/l to 0.29 nmol/l.
I've tried Boron to lower the SHBG and it doesn't really make much of a difference

Your FT is by no means low as the testing methods used are inaccurate.

To truly know where your FT levels sit one would need to have FT tested using the gold standard Equilibrium Dialysis or Ultrafiltration or simply use the newer calculated TruT Free Testosterone Calculator by FPT.....which has been shown to be on par with results obtained by the gold standard Equilibrium Dialysis

If we use the newer calculated TruT.....even with having a high SHBG 57.4 nmol/L..... seeing your TT is robust 26.4 nmol/L (760.8 ng/dL) your FT is by no means low but sub-par as it would be just under mid-range (reference range 16-31 ng/dL).....simply because the FT testing methods you had done are inaccurate as in your 1st set of results the linear law-of-mass action model Vermeulen calculated method was used which has been shown to be inaccurate and in the second set of labs they used the direct analog assay which is inaccurate an no longer recommended!



Why TruT™?
The only FDA-registered free testosterone calculator

• Improved biophysical characterizations have have suggested the importance of models that consider allosteric coupling of testosterone with dimeric SHBG. This model, as implemented by TruT™ provides the most accurate estimates for free testosterone.
• Commonly available free testosterone calculators (issam.ch, nebido.com, pctag.uk) use models of testosterone:SHBG binding (proposed by Vermeulen et al. and Sodergard et. al) which were developed before the crystal structure for SHBG:T complexes were available. These models assume that the two SHBG monomers behave identically in binding testosterone. Detailed experimental data show that the "simplified linear model is erroneous." References.
• The Endocrine Society has issued position statements which highlights the laboratory- and operator-dependent variability inherent in direct free testosterone measurements. For this reason they advocate for indirect "calculator" based methods References.
• The TruT™ calculator provides the ideal solution by using measurements of total testosterone, SHBG, and albumin to calculate free testosterone while taking into account the complex, non-linear allostery in SHBG's association with testosterone. TruT™ is the only calculator available that uses this more complex formulation. References

About TruT™ Free Testosterone Calculator


About TruT™

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 free-T 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.








To give you more insight using the newer TruT calculated method if we take your TT 26.4 nmol/L, SHBG 57.4 nmol/L and Albumin 45 g/L than converted to 4.5 g/dL than your FT is 22.84 ng/dL (just under the mean 23.5 ng/dl which would be just under mid-range of the reference range 16-31 ng/dL)

Now could we say your FT levels are sub-par.....definitely as you may very well need FT in the top end of the range seeing as you are experiencing low-t symptoms.....but let's be very clear your FT levels are by no means LOW!

 

[madman]

Can we ask how old you are?
With that level of SHBG most of your T is definitely bound up and your freeT level shows that.
Should you be a candidate for therapy you would definitely need a decent dose to come over the top of that SHBG and allow your FreeT to climb.
Would like to see a little more background and possibly thyroid numbers as well.

Not as much as one would think.....due to the newer understanding of SHBG:T binding.

Unfortunately his FT levels on labs are showing low due to the inaccurate FT testing methods used and if anything his FT is just below mid range using the newer calculated TruT method.

Schematic representation of experimental models of testosterone binding to SHBG. (a) Linear model of testosterone (T) binding to SHBG as conceptualized by Vermeulen et al. (3), Södergard et al.(4), and Mazer (5).

(b) New model (ZBJ, schematic adaptation) proposed by Zakharov et al. (34) incorporating the dynamics of allosteric regulation in testosterone binding to SHBG.

The different shapes represent conformationally distinct states of SHBG in the dynamic repartitioning of free testosterone into bound forms.

Recent evidence derived from new biophysical techniques indicates that the binding of testosterone to SHBG is a dynamic, multistep process.

*The binding of one molecule of testosterone to the first binding site on an SHBG dimer leads to conformational rearrangement and allostery between the two binding sites, such that the second testosterone molecule binds to the second binding site with a different binding affinity; there is readjustment of equilibria between these interconverting microstates.

This multistep, allosteric model provides validated estimates of free testosterone, which have close correspondence with values measured using equilibrium dialysis.

 

[bagelmatic]

Well i appreciate the replies ofcourse, but is there any advice anyone can give me as to what i can take/do to improve my situation?
i would HEAVILY appreciate this

 

[Systemlord]

Thanks for the replies so far guys @Systemlord @Sean Mosher
To answer your questions
-i'm 26 years old
here's more information about my thyroid
View attachment 7754

I've gone to two private endocrinologists and they were reluctant to put me on thyroid medication and we tried diet changes/supplement changes but nothing really worked

As I expected, Reverse T3 is below range because you have conversion problems which seem to favor Free T4, only Free T3 is the active thyroid hormone which increases metabolism.

Free T3 should be at least mid-range or better to support proper metabolic function, Free T3 provides energy to all organs so when Free T3 is low, organ function slows down.

I don't believe Free T is even close to optimal, more like sub-optimal and do not expect managed healthcare doctors to approve TRT with those numbers. If this is the case your only option would be a private anti-aging clinic.

I'm getting a Free T percentage of 1.54 %, 2-3 percent is considered normal.

You'll probably need levels >800 to get Free T to the optimal ranges and managed healthcare doctors are unable to allow levels >800 do to insurance guidelines.

Insurance guidelines and managed healthcare doctor are still in the stone ages for knowledge in TRT, so it's makes little sense to seek treatment in managed healthcare.

 

[bagelmatic]

As I expected, Reverse T3 is below range because you have conversion problems which seem to favor Free T4, only Free T3 is the active thyroid hormone which increases metabolism.

Free T3 should be at least mid-range or better to support proper metabolic function, Free T3 provides energy to all organs so when Free T3 is low, organ function slows down.

I don't believe Free T is even close to optimal, more like sub-optimal and do not expect managed healthcare doctors to approve TRT with those numbers. If this is the case your only option would be a private anti-aging clinic.

I'm getting a Free T percentage of 1.54 %, 2-3 percent is considered normal.

You'll probably need levels >800 to get Free T to the optimal ranges and managed healthcare doctors are unable to allow levels >800 do to insurance guidelines.

Insurance guidelines and managed healthcare doctor are still in the stone ages for knowledge in TRT, so it's makes little sense to seek treatment in managed healthcare.

I'll be going privately through a clinic for sure, i'm in the UK and the NHS is completely useless and will only treat you if you're basically dying...
This problem has put a large halt in my life right now and i'd be willing to do pretty much anything to fix it and money [within reason] isn't a problem.

What would you suggest i do about my FT3?

Also i've heard that TRT would also likely lower my SHBG, are there any other alternatives?
I have no problem taking TRT tbh as i'd just freeze my sperm beforehand and then run a course of TRT + HCG

 

[fifty]

I would look at thyroid and prolactin first. Trt is a pain in the ass.

Consider cabergoline and dhea.

 

[Systemlord]

I'll be going privately through a clinic for sure, i'm in the UK and the NHS is completely useless and will only treat you if you're basically dying...

This is how sick care operates, their job is to keep you alive, not optimize health. Add to the fact the NHS is underfunded and doesn't have the funds for every man that walks in with low testosterone.

What would you suggest i do about my FT3?

T3 only thyroid medicine, it's your only option. If you throw T4 medicine at the conversion problem, not much will change.

Also i've heard that TRT would also likely lower my SHBG, are there any other alternatives?

There is not much you can do about it, you have to play the hand you are dealt. More frequent injections has seen my SHBG increase 7 points.

 

[bagelmatic]

This is how sick care operates, their job is to keep you alive, not optimize health. Add to the fact the NHS is underfunded and doesn't have the funds for every man that walks in with low testosterone.



T3 only thyroid medicine, it's your only option. If you throw T4 medicine at the conversion problem, not much will change.



There is not much you can do about it, you have to play the hand you are dealt. More frequent injections has seen my SHBG increase 7 points.

How do you feel before you took testosterone vs how you feel now? and i'll look into the t3 medicine with my endocrinologist

 

[bagelmatic]

I would look at thyroid and prolactin first. Trt is a pain in the ass.

Consider cabergoline and dhea.

I got my prolactin down to 171 recently by a change in diet + taking calcium D glucarate and ashwagandha

What would taking DHEA do? i think i got my DHEA tested and it was fine

 

[Systemlord]

How do you feel before you took testosterone vs how you feel now? and i'll look into the t3 medicine with my endocrinologist

I felt amazing on TRT before the iron deficient took hold and forced me off TRT while I recover and rebuild my iron stores. I plan on restarting TRT in a couple weeks in nothing improves.

It only took 4.5 weeks to my natural production to turn back on, 4th week I could feel testosterone cycle down to zero, then 3 days later I started feeling good again. There are days I feel really good and others not so good.

 

[bagelmatic]

I felt amazing on TRT before the iron deficient took hold and forced me off TRT while I recover and rebuild my iron stores. I plan on restarting TRT in a couple weeks in nothing improves.

It only took 4.5 weeks to my natural production to turn back on, 4th week I could feel testosterone cycle down to zero, then 3 days later I started feeling good again. There are days I feel really good and others not so good.

Was your iron low before TRT, why did you have to stop TRT to bring back up your iron?

Sorry for the questions, i'm just trying to suck in as much knowledge as possible whilst giving out any i know

 

[Systemlord]

Was your iron low before TRT, why did you have to stop TRT to bring back up your iron?

Sorry for the questions, i'm just trying to suck in as much knowledge as possible whilst giving out any i know

Going on TRT worsened the iron deficiency and I was in and out of the hospital with bilateral edema in legs and swelling in the abdomen. Tongue was also swelling and very pale.

There wasn't much choice but to stop TRT and replenish my iron.

 

[bagelmatic]

Going on TRT worsened the iron deficiency and I was in and out of the hospital with bilateral edema in legs and swelling in the abdomen. Tongue was also swelling and very pale.

There wasn't much choice but to stop TRT and replenish my iron.

Wow, did you do a HCG + clomid restart for your testicles or did you just wait it out for your T levels to restore naturally?

I hope you get better soon and can hop back on TRT and feel great again tbh

 

[madman]

Well i appreciate the replies ofcourse, but is there any advice anyone can give me as to what i can take/do to improve my situation?
i would HEAVILY appreciate this

Contact Dr. Robert Stevens

HOW TO GET TRT IN THE UK

 

[bagelmatic]

Contact Dr. Robert Stevens

HOW TO GET TRT IN THE UK

I did in the past, he told me i don't need TRT and i should try boron to lower my SHBG
Which Didn't work, might contact him again to see what he says though... as he was one of only three TRT doctors in the UK to actually message me back personally which is highly appreciated

 

[Systemlord]

Wow, did you do a HCG + clomid restart for your testicles or did you just wait it out for your T levels to restore naturally?

I hope you get better soon and can hop back on TRT and feel great again tbh

I stopped TRT cold turkey and 4 weeks later could feel testosterone zero out, then 3 days later natural T returned. I figure even though iron is restored, recovery must still occur and it's not going to happen overnight.

I was on TRT for 2.5 years.

Thanks for the kind words.