SHBG: Does it just bind and render androgens useless or does it have a purpose?

[johndoesmith]

SHBG is mentioned a LOT on this forum, and often many men are unhappy with their levels. Very few comments regarding SHBG are positive in nature, in fact SHBG is seen as a problem by many, and in the steroid community it is seen as something that needs to be lowered otherwise it'll "steal" all of your free testosterone.

SHBG levels are incredibly difficult to manipulate, as there are many many hormones involved in its regulation. [1]

SHBG has a role[2], a function[3], and even a receptor[4][5].

In short, SHBG is quintessential to the proper hormonal functioning of men and women. Levels that are too low, or too high, have negative consequences, as always with hormones it is about balance.

[1] http://www.sciencedirect.com/science/article/pii/0960076091903102
[2]http://dx.doi.org.sci-hub.cc/10.1016/1043-2760(95)00162-X
[3] http://journals.sagepub.com/doi/pdf/10.1177/000456329002700603
[4] http://www.jbc.org/content/265/11/6048.short
[5] http://www.sciencedirect.com/science/article/pii/S0960076099000709

An interesting excerpt.

A number of models'"?' depicting hormonedelivery by dissociation have been proposed butthe factors governing the kinetics of dissociationand tissue uptake remain contentious.P:"However in all situations studied to date, spontaneousdissociation of the protein-hormonecomplex is sufficiently rapid to account for theobserved tissue uptake

http://journals.sagepub.com/doi/pdf/10.1177/000456329002700603

For some fun filled reading, the free hormone hypothesis vs free hormone transport hypothesis is an entertaining and stimulating read. http://dx.doi.org.sci-hub.cc/10.1210/edrv-10-3-232

 

[MikeXL]

Great point. If you are saying that people are always trying to lower their SHBG like it is the devil and that this is an overly simplistic view, I couldn't agree more.

Now I am not saying that SHBG doesn't matter

But here is something that I always like to point out

lowering SHBG not only frees up your testosterone, it frees up your DHT and estrogen. Most people don't even know that there is something called free estradiol or free DHT

Remember your quest for more free T can give you more free E

Also, remember that the testosterone that you free up is free to aromatize into E2 and reduce to DHT

 

[johndoesmith]

Great point. If you are saying that people are always trying to lower their SHBG like it is the devil and that this is an overly simplistic view, I couldn't agree more.

Now I am not saying that SHBG doesn't matter

But here is something that I always like to point out

lowering SHBG not only frees up your testosterone, it frees up your DHT and estrogen. Most people don't even know that there is something called free estradiol or free DHT

Remember your quest for more free T can give you more free E

Also, remember that the testosterone that you free up is free to aromatize into E2 and reduce to DHT

The more I dug into the free hormone hypothesis vs free hormone transport hypothesis, the more I got confused. See, academic research often contradicts what happens in real life, such as the other study I posted that suggests TRT + high dose AI prevents HPTA shutdown. We all know that this is not how it works.

I don't think that lowering SHBG slightly, say from 35-20 will make a huge change in free E2, as E2 does not have as high of an affinity for SHBG. DHT>Test>E2 is the preference, so it's more of an indirect effect of increasing E2.

More free test = more E2. It's the same thing at the end of the day but since we're talking mechanism here, I figured it'd be interesting.

I actually had my free estradiol levels ran recently.

 

[MikeXL]

Yes. I agree it is confusing. So I think for know we have to hedge our bets.

I see from you order of affinity you have read Crisler's book. My understanding is that John believes that high levels of DHT don't matter unless it is affecting HCT. I am not so sure that is the case.

 

[MikeXL]

Johndoesmith - I tried sending you a PM. but your message box is full

 

[johndoesmith]

Yes. I agree it is confusing. So I think for know we have to hedge our bets.

I see from you order of affinity you have read Crisler's book. My understanding is that John believes that high levels of DHT don't matter unless it is affecting HCT. I am not so sure that is the case.

I actually haven't read crisler's book, unless you mean "a recipe for success". Most of my knowledge comes clinical studies, different endocrinology texts(endotext.com is a great resource! you can spend days there), different patterns I have observed from seeing people's labs and talking to them about symptoms, and from talking to people much much more intelligent than myself(Dr Saya, nelson vergel, pharmacists who are online, med students, and other clinicians).

The binding affinity of SHBG's ligands is pretty well published.

Some things that Dr john has said, have left me dubious of some of his claims, but he is still known as a pioneer in the field!

 

[johndoesmith]

Johndoesmith - I tried sending you a PM. but your message box is full

Thanks for the heads up I fixed it.

 

[MikeXL]

ok. sent to you a PM<

Thanks for the heads up I fixed it.

 

[ERO]

Those of us that suffer from low SHBG can tell you from experience that lower is NOT better. As with everything else, balance is key - not too high, not too low.

 

[MikeXL]

How has low SHBG affected you?

Those of us that suffer from low SHBG can tell you from experience that lower is NOT better. As with everything else, balance is key - not too high, not too low.

 

[ERO]

Guys with low SHBG very much under-respond to TRT. Personally, I don't feel anything from it - its like I am injecting water. Plus I am with the best doctor and on a cutting edge protocol.

Google "Low SHBG TRT" (no quotes) and you will see.

 

[MikeXL]

Interesting ERO

 

[eli]

That's why I've been on ment and feel great, because of my low shbg. Trt was just a pain in the ass. I'll update everyone in 8 weeks, I wanna be on trest for a while before I say this is the drug for low or high shbg

 

[green2145]

What causes low SHBG if you're not pre-diabetic or insulin resistant? Genetics?