low shbg means high free E2 ?

[AndroChishti]

Hello all,

I have seen this idea thrown around on trt and steroids forums that low SHBG causes high free E2 and that the use of DHT derivatives like Proviron, Anavar can cause gyno by lowering shbg = > high free Test => more aromatization.

But as per this study SHBG preferentially binds to DHT with affinity 5 times more than Testosterone and 20 times more than Estradiol. So if a person has low SHBG they should have way more free DHT available than free E2 (ratio is 20:1 as per the affinities) which implies that the balance of DHT to E2 is skewed towards DHT and the said user should be feeling low E2 sides even when the blood work shows normal E2 levels.

Is this plausible or am I missing something. Anyone can shed light on this, that would be great.

 

[Gman86]

That’s some interesting info. Don’t think u have to think that deeply into it tho. But doesn’t hurt. The more u know and understand about something the better obv. What’s ur SHBG level?

Think u can just keep things fairly simple tho and just generally try to keep SHBG in a healthy range. Just like with everything else, SHBG is all about balance. But like with quite a few other hormones, like E2 and test, for example, low is much worse than high, at least imo. They’re finding out that SHBG isn’t just a protein that binds up add hormones, it’s actually needed to help get hormones into cells. At least from my understanding. And low SHBG causes hormones to fluctuate much more than someone with a normal SHBG, and it seems to cause more issues for these guys than men with normal, or even higher end SHBG levels. I would say u want to try and keep ur SHBG around 20-50, from what I’ve seen anecdotally.

 

[Charliebizz]

Hello all,

I have seen this idea thrown around on trt and steroids forums that low SHBG causes high free E2 and that the use of DHT derivatives like Proviron, Anavar can cause gyno by lowering shbg = > high free Test => more aromatization.

But as per this study SHBG preferentially binds to DHT with affinity 5 times more than Testosterone and 20 times more than Estradiol. So if a person has low SHBG they should have way more free DHT available than free E2 (ratio is 20:1 as per the affinities) which implies that the balance of DHT to E2 is skewed towards DHT and the said user should be feeling low E2 sides even when the blood work shows normal E2 levels.

Is this plausible or am I missing something. Anyone can shed light on this, that would be great.

Omg. I’ve been saying this to my wife for a while. I have move low e2 symptoms the high. And I’m a low shbg guy. My e2 is only a pont or 2 over the range. But I’m starting to think everything we thought we knew about shbg is the exact opposite. I’ve tried everything that low shbg guys are “supposed to do” and usually feel worse. I’m really thinking about raising my dose and going to less frequent injections like 2x a week or something.

 

[JA Battle]

I wonder how many guys have actually targeted mid range for all hormones? Probably not many have whole heartedly tried.

 

[Charliebizz]

I wonder how many guys have actually targeted mid range for all hormones? Probably not many have whole heartedly tried.

I’ve tried to aim for mid range in testosterone. But with low shbg my tt is mid range and free t is over the top.

 

[bochinit]

My shbg is low and I'm trying to microdose my testosterone because any high dosage seems to spike my levels and e2 and I end up with extreme anxiety. I'm sufering a lot with it. Anxiety is no joke..

 

[bixt]

I have seen this idea thrown around on trt and steroids forums that low SHBG causes high free E2 and that the use of DHT derivatives like Proviron, Anavar can cause gyno by lowering shbg = > high free Test => more aromatization.

More than this idea is the firm belief on BB forums that DHT can actually override and overrule E2. Various DHT compounds such as proviron and masteron are used to alleviate high E2 symptoms such as water retention.

I can corroborate for myself that this is the case. Many times when experimenting with highly aromatisable compounds such as MENT and dbol, I have experienced water retention. BOTH arimidex and dht compounds (masteron and winstrol) used in excess (at different times) resulted in the same low E2 symptoms (mainly creaking knees and wrist pain for me, within a day or two). Both also solved the water almost immediately. It was almost as if they were the same compound! (at least as far as joint creaking and water elimination went. The winstrol was not fake - the strength gains were incredible)

 

[Systemlord]

I wonder how many guys have actually targeted mid range for all hormones?

I thrive at 470-550 and have low SHBG. These Total T levels produce Free T in the 20-25 pg/mL ranges.

My E2 runs 50+ at these levels and I feel fine.

 

[Gman86]

More than this idea is the firm belief on BB forums that DHT can actually override and overrule E2. Various DHT compounds such as proviron and masteron are used to alleviate high E2 symptoms such as water retention.

I can corroborate for myself that this is the case. Many times when experimenting with highly aromatisable compounds such as MENT and dbol, I have experienced water retention. BOTH arimidex and dht compounds (masteron and winstrol) used in excess (at different times) resulted in the same low E2 symptoms (mainly creaking knees and wrist pain for me, within a day or two). Both also solved the water almost immediately. It was almost as if they were the same compound! (at least as far as joint creaking and water elimination went. The winstrol was not fake - the strength gains were incredible)

What doses of masteron and Winstrol were u using?

 

[bixt]

What doses of masteron and Winstrol were u using?

I really play around with stuff, acute doses, short term.

Masteron from 3mg a day to 20mg a day. Besides dryish joints not stuff I can FEEL surprisingly. No libido boost for me surprisingly.

Winstrol from 7.5mg to 30mg a day. 30mg a day all at once in the AM- instant kick in libido x 5, exuberance, insane confidence, lasts the whole day. Its unsustainable after a week though and need a break to get that "high" again. So im going to attribute the libido, confidence to raised dopamine, which falls to baseline after a few days.

I guess I cant state my Tren experiance on this forum lol. PM me.

Why do I say dopamine? Because I have experimented with substances which raise dopamine (and serotonin) acutely. Thus, I can tell.

 

[AndroChishti]

I thrive at 470-550 and have low SHBG. These Total T levels produce Free T in the 20-25 pg/mL ranges.

My E2 runs 50+ at these levels and I feel fine.

Shouldnt the unit for Free Testosterone be ng/dL ?

 

[Systemlord]

Shouldnt the unit for Free Testosterone be ng/dL ?

Labcorp's Free T is in pg/mL, the Total T is in ng/dL.

 

[Cataceous]

It's great when someone comes along and forces us to re-examine previous assumptions. If in experimenting with a free estradiol calculator you decrease SHBG while keeping free testosterone the same then you do see an increase in free estradiol, and an even larger increase in free DHT. But I'm starting to think the correct approach is to hold free estradiol and free DHT constant. These metabolites are created from free testosterone, so why should they change if free testosterone is fixed along with the underlying clearance rate constants? As with testosterone, the creation or input rate is driving the free hormone levels, and the total levels go where necessary according to SHBG, albumin, etc.

The first thing I wanted to see is if my own data support the idea that free estradiol is proportional to free testosterone. I have a few datapoints that are uncontaminated by AI or hCG use:

This is using the Mult-Ligand model. Not a perfect fit, but still within reason.

In any case, if this idea is correct then the interesting implication is that varying SHBG does not affect free estradiol or free DHT, in addition to free testosterone.

Things get more complex with the addition of exogenous DHT or an analog. This effectively drives up free DHT. In the absence of additional aromatase inhibition, free T and free E2 would not change after equilibrium is restored. But the total hormone levels would be different. If higher free DHT reduces aromatization then there could be a decrease in free estradiol and a small change in free testosterone.

 

[AndroChishti]

Labcorp's Free T is in pg/mL, the Total T is in ng/dL.

Isnt it weird since the free Test is suppose to be ~2% of total Test ?

 

[AndroChishti]

It's great when someone comes along and forces us to re-examine previous assumptions. If in experimenting with a free estradiol calculator you decrease SHBG while keeping free testosterone the same then you do see an increase in free estradiol, and an even larger increase in free DHT. But I'm starting to think the correct approach is to hold free estradiol and free DHT constant. These metabolites are created from free testosterone, so why should they change if free testosterone is fixed along with the underlying clearance rate constants? As with testosterone, the creation or input rate is driving the free hormone levels, and the total levels go where necessary according to SHBG, albumin, etc.

The first thing I wanted to see is if my own data support the idea that free estradiol is proportional to free testosterone. I have a few datapoints that are uncontaminated by AI or hCG use:
View attachment 18869
This is using the Mult-Ligand model. Not a perfect fit, but still within reason.

In any case, if this idea is correct then the interesting implication is that varying SHBG does not affect free estradiol or free DHT, in addition to free testosterone.

Things get more complex with the addition of exogenous DHT or an analog. This effectively drives up free DHT. In the absence of additional aromatase inhibition, free T and free E2 would not change after equilibrium is restored. But the total hormone levels would be different. If higher free DHT reduces aromatization then there could be a decrease in free estradiol and a small change in free testosterone.

First of all, thank you for such a detailed response. Do you think that If someone were to decrease their SHBG then only their Total Testosterone (TT) will decrease and Free Testosterone (FT) remain unchanged?

If that is the case, then SHBG should not have any effect symptom resolution or is it working through some other mechanism.

 

[Cataceous]

... Do you think that If someone were to decrease their SHBG then only their Total Testosterone (TT) will decrease and Free Testosterone (FT) remain unchanged?
...

Yes. The basic argument is that if you're introducing testosterone at a constant rate, as when absorbing testosterone from an injection site, then at steady state you must be metabolizing and eliminating testosterone at the same rate. If we can assume that the law of mass action is largely applicable in the clearance process then free testosterone must be proportional to the rate at which testosterone is introduced. Thus free testosterone is independent of SHBG/albumin/etc., and total testosterone should be viewed as the dependent variable. I've been putting forth this hypothesis for some time now and it hasn't been shot down yet. At least one or two formal studies have data that provide some indirect support. Until you brought up the subject I hadn't considered that the same principle should apply to the testosterone metabolites.

...
If that is the case, then SHBG should not have any effect symptom resolution or is it working through some other mechanism.

Very likely the latter. Let me quote "James" from over at PeakTestosterone.com, who wrote this in response to a question on why low SHBG is a problem:

1.) Free SHBG plays a role in intracellular AR signalling. The rate of glucuronidation and time before effluxion of a free testosterone molecule that has entered a cell is mediated by intracellular SHBG brought into the cell via the megalin receptor. This phenomenon is tissue specific, and some cells produce their own SHBG internally to achieve this result. ​

​

2.) Free SHBG also plays a role in extracellular signalling. A receptor, known as SHBG-R, binds to free SHBG which then "catches" various steroid molecules to complete a signalling pathway believed to be related to C-AMP. There is a pinned post regarding this phenomenon, and Dr. Crisler wrote an article about it. ​

and in another post:

First:​

SHBG-R is a major regulator of cellular cAMP which upregulates AR production. If you have low AR expression, your T levels are entirely worthless. T cannot induce transcriptional changes without AR protien. ​

​

The extracellular SHBG-R receptor is responsible for upregulating cAMP and PKA. Studies have shown increases in cAMP by up to 600% when SHBG binds to extracellular SHBG-R and the SHBG glycoprotein then bonds with a free E2 molecule. (SHBG is a homodimer, with one dimer being able to bind to megalin and the second to a free steroid moleucle.) SHBG alone also triggers an effect at SHBG-R, but only 20-100%. Free hormones do not trigger any such cAMP increase. SHBG-DHT and SHBG-T do not trigger any increase. Only SHBG-E2.​

​

Second:​

SHBG bound T is actually active in certain tissue. SHBG-T binds to the extracellular megalin protien. The SHBG-T complex is then brought into cellular cytoplasm via endocytosis (the cell wall wraps itself around the complex.) Once in cytoplasm, the SHBG-T complex is degraded within organelles called lysosomes. The free T molecule may then bind with an AR protein and pass through the nuclear membrane into the nucleus where it will eventually bind to directly to DNA at HREs (hormone responsive elements), specifically AREs, and induce transcriptional changes.​

​

Third:​

Studies have shown that T-responsive tissue responds LESS to pure FT alone than it does when exposed to T+SHBG. The researchers note that when exposed to T without SHBG, T that enters the cell via passive diffusion is rapidly glucuronidated and effluxed. They surmise that SHBG (which enters the cell via megalin/endocytosis) prolongs the lifetime of T within the cell itself, and not just in serum.​

 

[bixt]

Thus free testosterone is independent of SHBG/albumin/etc., and total testosterone should be viewed as the dependent variable.

Very very interesting! How would you say does this development fit in with models such as TruT? Until now we have all passed comments such as "with such and such a dose, and a low SHBH, your free T must be sky high".

 

[Cataceous]

Very very interesting! How would you say does this development fit in with models such as TruT? ...

I'd say these ideas are complementary to free testosterone calculations such as Vermeulen and Tru-T. The calculations describe the relationship between SHBG, albumin, total testosterone and free testosterone. We're just changing things around by asking that total testosterone now be an output rather than an input.

... Until now we have all passed comments such as "with such and such a dose, and a low SHBH, your free T must be sky high".

Perhaps the comment should instead be "with such and such a dose, and a low SHBH, your total T must be relatively low". More commonly it would be "with high total T, and a low SHBH, your free T must be sky high". That is, low SHBG and normal free T implies lowish total T.

 

[equel]

Im late to the party. So what does this mean in practise? How should one go about to be optimized having low shbg?

 

[GreenMachineX]

Im late to the party. So what does this mean in practise? How should one go about to be optimized having low shbg?

Bump for this. I'm a low SHBG guy as well and having a very hard time getting dialed in. Total T is 550 and free T is very top of range, and e2 is 18. Having crippling anxiety, palpitations, insomnia...

Although I am dropping my fish oil dose because apparently that lowers SHBG.