Peak Testosterone Forum

General Category => Testosterone, Hormones and General Men's Health => Topic started by: Dr. John Crisler on November 29, 2017, 07:06:56 am

Title: More on How SHBG Really Works
Post by: Dr. John Crisler on November 29, 2017, 07:06:56 am
http://drjohncrisler.com/how-sex-hormone-binding-globulin-shbg-really-works.html
Title: Re: More on How SHBG Really Works
Post by: PeakT on November 29, 2017, 01:53:52 pm
Will close your first thread after Pakman sees it.
Title: Re: More on How SHBG Really Works
Post by: PakMan on November 30, 2017, 01:56:24 am
http://drjohncrisler.com/how-sex-hormone-binding-globulin-shbg-really-work.html

So T\E\DHT can have an effect even when they are bound to SHBG?
Title: Re: More on How SHBG Really Works
Post by: IamTheOneWhoKnocks on November 30, 2017, 02:11:47 am
This may be why a good T to E ratio is needed. Too much of one or the other and one will be over powering by binding to SHBG? With so many other things out there that needs research, and Testosterone has been taboo for so long, it is good to see some research happening. I see so many men who say injecting T is like injecting water. I feel for these guys.
Title: Re: More on How SHBG Really Works
Post by: SHBetaG on November 30, 2017, 10:06:06 am
Moral of the story: go buy some SHBG instead testosterone. /s

Just an idea: maybe low SHBG guys should try to push their free taistelee through the roof, since they don't have much of that SHBG mediated testosterone action?

PeakT: sweet podcast!
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 03, 2017, 07:29:46 am
http://drjohncrisler.com/how-sex-hormone-binding-globulin-shbg-really-work.html

So T\E\DHT can have an effect even when they are bound to SHBG?
Yes, but only if SHBG has first attached to its receptor on the cell membrane, THEN a T, or E, binds to it.

What we usually think of is the SHBG/T or SHBG/E, for instance, which is floating around in the blood. The latters are inert.
Title: Re: More on How SHBG Really Works
Post by: doin it on December 03, 2017, 08:22:12 am

So, is there a formula to calculate how much SHBG has attached itself to the various receptors and has therefore become biologically active with respect to T and E2 ?

And does this amount of SHBG get subtracted from the total SHBG number, leaving the balance inert ?
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 03, 2017, 05:45:20 pm

So, is there a formula to calculate how much SHBG has attached itself to the various receptors and has therefore become biologically active with respect to T and E2 ?

And does this amount of SHBG get subtracted from the total SHBG number, leaving the balance inert ?
Excellent question!

If anyone has figured out a way to quantify the effects of SHBG binding to its receptor on the cell membrane, I am unaware of it.

They can know how much SHBG is bound, by using immunoassay techniques. That is where you put a tag on a SHBG molecule, then watch it light up while stuck to the cell membrane. But this is not a commercially available test....and, s I said, we don't know what to do with it yet, anyway.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 03, 2017, 05:55:02 pm
http://drjohncrisler.com/how-sex-hormone-binding-globulin-shbg-really-work.html

So T\E\DHT can have an effect even when they are bound to SHBG?
ONLY when the SHBG first bound to its receptor on the cell membrane. Then they all activate pathways inside the cell.

...but not when they bind to SHBG that is floating in the bloodstream.
Title: Re: More on How SHBG Really Works
Post by: doin it on December 03, 2017, 07:09:53 pm

So, is there a formula to calculate how much SHBG has attached itself to the various receptors and has therefore become biologically active with respect to T and E2 ?

And does this amount of SHBG get subtracted from the total SHBG number, leaving the balance inert ?
Excellent question!

If anyone has figured out a way to quantify the effects of SHBG binding to its receptor on the cell membrane, I am unaware of it.

They can know how much SHBG is bound, by using immunoassay techniques. That is where you put a tag on a SHBG molecule, then watch it light up while stuck to the cell membrane. But this is not a commercially available test....and, s I said, we don't know what to do with it yet, anyway.

--

So, this begs the question: Do I really want to lower a "high" SHBG blood test result ?  Since there is apparently no way to determine (under this hypothesis), how much SHBG has attached to the various target receptors, and is therefore biologically active T and E-wise, maybe I like having a "high" SHBG result ???

Title: Re: More on How SHBG Really Works
Post by: doin it on December 03, 2017, 08:23:28 pm

And, if SHBG, like many other biochems, has subfractions (not yet identified), one may have an affinity for T, one for E2, E1, DHT, etc.

And, if so, we may want an abundance of SHBG-a (DHT?) and associated receptors here (organ), and abundance of SHBG-b (T) there, but only a small amount of SHBG-b (T) in another place as well as a small amount of SHBG- c  someplace else, and some amount of SHBG-d (E2) in yet one more place, etc. ???

Title: Re: More on How SHBG Really Works
Post by: vvs1 on December 03, 2017, 08:53:04 pm

So, is there a formula to calculate how much SHBG has attached itself to the various receptors and has therefore become biologically active with respect to T and E2 ?

And does this amount of SHBG get subtracted from the total SHBG number, leaving the balance inert ?
Excellent question!

If anyone has figured out a way to quantify the effects of SHBG binding to its receptor on the cell membrane, I am unaware of it.

They can know how much SHBG is bound, by using immunoassay techniques. That is where you put a tag on a SHBG molecule, then watch it light up while stuck to the cell membrane. But this is not a commercially available test....and, s I said, we don't know what to do with it yet, anyway.

--

So, this begs the question: Do I really want to lower a "high" SHBG blood test result ?  Since there is apparently no way to determine (under this hypothesis), how much SHBG has attached to the various target receptors, and is therefore biologically active T and E-wise, maybe I like having a "high" SHBG result ???

But...maybe a high shbg number means that there's less shbg in the cells, therefore less binding leading to low t symptoms?
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 05, 2017, 05:55:22 am

So, is there a formula to calculate how much SHBG has attached itself to the various receptors and has therefore become biologically active with respect to T and E2 ?

And does this amount of SHBG get subtracted from the total SHBG number, leaving the balance inert ?
Excellent question!

If anyone has figured out a way to quantify the effects of SHBG binding to its receptor on the cell membrane, I am unaware of it.

They can know how much SHBG is bound, by using immunoassay techniques. That is where you put a tag on a SHBG molecule, then watch it light up while stuck to the cell membrane. But this is not a commercially available test....and, s I said, we don't know what to do with it yet, anyway.

--

So, this begs the question: Do I really want to lower a "high" SHBG blood test result ?  Since there is apparently no way to determine (under this hypothesis), how much SHBG has attached to the various target receptors, and is therefore biologically active T and E-wise, maybe I like having a "high" SHBG result ???

But...maybe a high shbg number means that there's less shbg in the cells, therefore less binding leading to low t symptoms?
Higher SHBG concentrations would mean more bound to the SHBG-R

But sex hormones levels would influence this too, as they bind the SHBG beforehand.
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 05, 2017, 07:54:00 pm

So, is there a formula to calculate how much SHBG has attached itself to the various receptors and has therefore become biologically active with respect to T and E2 ?

And does this amount of SHBG get subtracted from the total SHBG number, leaving the balance inert ?
Excellent question!

If anyone has figured out a way to quantify the effects of SHBG binding to its receptor on the cell membrane, I am unaware of it.

They can know how much SHBG is bound, by using immunoassay techniques. That is where you put a tag on a SHBG molecule, then watch it light up while stuck to the cell membrane. But this is not a commercially available test....and, s I said, we don't know what to do with it yet, anyway.

--

So, this begs the question: Do I really want to lower a "high" SHBG blood test result ?  Since there is apparently no way to determine (under this hypothesis), how much SHBG has attached to the various target receptors, and is therefore biologically active T and E-wise, maybe I like having a "high" SHBG result ???

Guys who take Danazol don’t seem to feel any different.  There could be other reasons I guess, but it makes you wonder.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 07, 2017, 06:23:08 am

So, is there a formula to calculate how much SHBG has attached itself to the various receptors and has therefore become biologically active with respect to T and E2 ?

And does this amount of SHBG get subtracted from the total SHBG number, leaving the balance inert ?
Excellent question!

If anyone has figured out a way to quantify the effects of SHBG binding to its receptor on the cell membrane, I am unaware of it.

They can know how much SHBG is bound, by using immunoassay techniques. That is where you put a tag on a SHBG molecule, then watch it light up while stuck to the cell membrane. But this is not a commercially available test....and, s I said, we don't know what to do with it yet, anyway.

--

So, this begs the question: Do I really want to lower a "high" SHBG blood test result ?  Since there is apparently no way to determine (under this hypothesis), how much SHBG has attached to the various target receptors, and is therefore biologically active T and E-wise, maybe I like having a "high" SHBG result ???

Guys who take Danazol don’t seem to feel any different.  There could be other reasons I guess, but it makes you wonder.
That's been my experience.

Taking Danazol w/ high(er) SHBG not on TRT: the boy readjusts, you end up where you started. Chasing one's own tail.

Taking Danazol after TRT: higher SHBG is better anyway.

Either case, adding a drug, wasting money.
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 07, 2017, 09:33:07 am
higher SHBG is better anyway.


Your take on this:

I've seen a number of higher SHBG guys - say 55+ - who don't feel good.  Coincidence?  Lack of treatment? 

I always assumed that they were having some kind of underlying (and poorly understood liver/hormonal) issue?
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 07, 2017, 09:54:19 am
higher SHBG is better anyway.


Your take on this:

I've seen a number of higher SHBG guys - say 55+ - who don't feel good.  Coincidence?  Lack of treatment? 

I always assumed that they were having some kind of underlying (and poorly understood liver/hormonal) issue?
Pre-TRT? Not enough left over to have enough to use.

After-TRT? Same as above, and/or Estrogen was too low.  The SHBG was gobbling it all up.
Title: Re: More on How SHBG Really Works
Post by: vvs1 on December 07, 2017, 10:45:36 am
higher SHBG is better anyway.


Your take on this:

I've seen a number of higher SHBG guys - say 55+ - who don't feel good.  Coincidence?  Lack of treatment? 

I always assumed that they were having some kind of underlying (and poorly understood liver/hormonal) issue?
Pre-TRT? Not enough left over to have enough to use.

After-TRT? Same as above, and/or Estrogen was too low.  The SHBG was gobbling it all up.

Is there a non-TRT protocol for high shbg for younger guys that have good T levels? 

My shbg has increased from mid 30s to 80, yet no real change in symptoms, so I know there's something else to the puzzle.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 07, 2017, 01:24:17 pm
From that same lecture:

SHBG

Sex Hormone Binding Globulin
Produced by liver (et al)
Binds sex hormones– androgens and estrogen,  androgens>estrogen
↑ by E, liver failure, growth hormone, hyperthyroidism, Thyroid Tx, working out
↓ by androgen, IGF-1, insulin
No real way to manipulate
Title: Re: More on How SHBG Really Works
Post by: Bravo5 on December 07, 2017, 02:31:11 pm
From that same lecture:

SHBG

Sex Hormone Binding Globulin
Produced by liver (et al)
Binds sex hormones– androgens and estrogen,  androgens>estrogen
↑ by E, liver failure, growth hormone, hyperthyroidism, Thyroid Tx, working out
↓ by androgen, IGF-1, insulin
No real way to manipulate

Guys with high SHBG are almost always slim/on the underweight side. Do you think increasing carbohydrates/lower GI has a chance to lower SHBG significantly?
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 07, 2017, 02:59:50 pm
From that same lecture:

SHBG

Sex Hormone Binding Globulin
Produced by liver (et al)
Binds sex hormones– androgens and estrogen,  androgens>estrogen
↑ by E, liver failure, growth hormone, hyperthyroidism, Thyroid Tx, working out
↓ by androgen, IGF-1, insulin
No real way to manipulate

Guys with high SHBG are almost always slim/on the underweight side. Do you think increasing carbohydrates/lower GI has a chance to lower SHBG significantly?
In thinking about this more, my recollection it is actually INFLAMMATION that decreases SHBG, rather than insulin per se.

Again, there is no practical way to alter SHBG.
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 08, 2017, 05:20:38 am
In thinking about this more, my recollection it is actually INFLAMMATION that decreases SHBG, rather than insulin per se.

Again, there is no practical way to alter SHBG.

Interesting comment.  Notice that this study concludes insulin is the prime driver.  However, inflammation falls with weight loss as well - not just insulin - something they don't appear to account for or measure in this study.  However, insulin has been shown in vitro to stimulate SHBG and so these researchers conclude it is an independent stimulator:

https://www.ncbi.nlm.nih.gov/pubmed/7962291

"It is known that there is an inverse relationship between the serum levels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported...During weight loss, insulin levels decreased at an average rate of 6.1 microU/mL per unit decrease in BMI, a much higher slope than the positive slope vs. BMI in weight stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the SHBG vs. insulin coordinates in the weight-losing subjects did not differ significantly from those expected from the SHBG vs. insulin equation in weight-stable subjects. The stability of the SHBG-insulin relationship during weight loss despite the profoundly altered relationship of each separate component to BMI strongly suggests a close metabolic link between SHBG and insulin. As SHBG is not known to alter the production or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion that the predictable inverse relationship between serum insulin and SHBG indicates that insulin controls SHBG synthesis in vivo."
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 08, 2017, 05:28:22 am
Okay, this gets really interesting really fast.  Could one make a case that SHBG is actually anti-inflammatory (like testosterone)?  Well, I don't know about that.  To me it looks like it's a middle man, but you never know...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457423/

"Although both TT and SHBG levels are significant predictors for the risk of MetS in our initial analyses, only SHBG retains its significance after adjustment of both TT and SHBG levels. Some studies have reported SHBG as a dominant predictor for prevalent and incident MetS, independent of TT, while TT lost its significance as a predictor for the risk of MetS after adjustment of SHBG16, 17. In our study, we also found that serum SHBG levels were significantly correlated with adiponectin and leptin levels even after controlling for age, lifestyle factors, BMI and TT level. Both adiponectin and leptin levels were significantly associated with all individual MetS components.

Adiponectin and leptin are two important cytokines secreted from adipose tissues that play important roles in the pathogenesis of MetS. Adiponectin has been found to have antidiabetic, anti-atherogenic, and anti-inflammatory properties, while leptin can regulate body weight by modulating appetite and energetic balance, and upregulate proinflammatory cytokines that are associated with insulin resistance and endothelial dysfunction5, 25. Aside from our study, only limited epidemiologic studies have evaluated the relationships among SHBG, adiponectin and leptin in men26–28. Gannage´-Yared et al. first reported that serum SHBG level was positively correlated with adiponectin level and negatively correlated with leptin level in men26. The relationship between SHBG and adiponectin persisted after adjustment for waist or BMI, while SHBG lost its relationship with leptin after adjustment for BMI26. "
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 08, 2017, 05:31:55 am
Is there is a insulin inflammation connection?  Sure and it is exemplified in adult onset diabetes:

https://www.webmd.com/diabetes/type-2-diabetes-guide/inflammation-and-diabetes#1

"How could carrying extra weight and sofa-sitting be connected to higher levels of inflammatory chemicals in the body and the development of diabetes?

Researchers discovered that in people with type 2 diabetes, cytokine levels are elevated inside fat tissue. Their conclusion: Excess body fat, especially in the abdomen, causes continuous (chronic), low levels of abnormal inflammation that alters insulin's action and contributes to the disease."
Title: Re: More on How SHBG Really Works
Post by: vvs1 on December 08, 2017, 07:09:39 pm
In thinking about this more, my recollection it is actually INFLAMMATION that decreases SHBG, rather than insulin per se.

Again, there is no practical way to alter SHBG.

Interesting comment.  Notice that this study concludes insulin is the prime driver.  However, inflammation falls with weight loss as well - not just insulin - something they don't appear to account for or measure in this study.  However, insulin has been shown in vitro to stimulate SHBG and so these researchers conclude it is an independent stimulator:

https://www.ncbi.nlm.nih.gov/pubmed/7962291

"It is known that there is an inverse relationship between the serum levels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported...During weight loss, insulin levels decreased at an average rate of 6.1 microU/mL per unit decrease in BMI, a much higher slope than the positive slope vs. BMI in weight stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the SHBG vs. insulin coordinates in the weight-losing subjects did not differ significantly from those expected from the SHBG vs. insulin equation in weight-stable subjects. The stability of the SHBG-insulin relationship during weight loss despite the profoundly altered relationship of each separate component to BMI strongly suggests a close metabolic link between SHBG and insulin. As SHBG is not known to alter the production or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion that the predictable inverse relationship between serum insulin and SHBG indicates that insulin controls SHBG synthesis in vivo."

I wonder if insulin injections would lower my shbg?

They always say to find the root cause, but regular doctors don't really know what to do or recognize it as a problem even if your free t % is low and out of range.
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 09, 2017, 03:05:06 pm


I wonder if insulin injections would lower my shbg?

They always say to find the root cause, but regular doctors don't really know what to do or recognize it as a problem even if your free t % is low and out of range.

Well, probably, but that's risky as heck, right?
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 10, 2017, 02:36:29 pm
In thinking about this more, my recollection it is actually INFLAMMATION that decreases SHBG, rather than insulin per se.

Again, there is no practical way to alter SHBG.

Interesting comment.  Notice that this study concludes insulin is the prime driver.  However, inflammation falls with weight loss as well - not just insulin - something they don't appear to account for or measure in this study.  However, insulin has been shown in vitro to stimulate SHBG and so these researchers conclude it is an independent stimulator:

https://www.ncbi.nlm.nih.gov/pubmed/7962291

"It is known that there is an inverse relationship between the serum levels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported...During weight loss, insulin levels decreased at an average rate of 6.1 microU/mL per unit decrease in BMI, a much higher slope than the positive slope vs. BMI in weight stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the SHBG vs. insulin coordinates in the weight-losing subjects did not differ significantly from those expected from the SHBG vs. insulin equation in weight-stable subjects. The stability of the SHBG-insulin relationship during weight loss despite the profoundly altered relationship of each separate component to BMI strongly suggests a close metabolic link between SHBG and insulin. As SHBG is not known to alter the production or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion that the predictable inverse relationship between serum insulin and SHBG indicates that insulin controls SHBG synthesis in vivo."
Taking anti-inflammatory supplements increases SHBG. In fact, more than 2 cups of green tea per day will do it.

They took my SHBG over 90!
Title: Re: More on How SHBG Really Works
Post by: sh1209 on December 10, 2017, 05:29:37 pm
So with all this information and everything that’s been said, ultimately what is the best way to treat a high shbg guy?
Title: Re: More on How SHBG Really Works
Post by: BBkingbluesking122 on December 10, 2017, 06:12:45 pm


I wonder if insulin injections would lower my shbg?

They always say to find the root cause, but regular doctors don't really know what to do or recognize it as a problem even if your free t % is low and out of range.

Well, probably, but that's risky as heck, right?

Funny
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 11, 2017, 03:43:03 pm
So with all this information and everything that’s been said, ultimately what is the best way to treat a high shbg guy?

The only way we have seen it on here from what I remember is a low T guy going on TRT.  You can also see if you have some underlying condition causing the problem and then try to correct it although no one has done that to date:

http://www.peaktestosterone.com/high_shbg.aspx
Title: Re: More on How SHBG Really Works
Post by: James on December 16, 2017, 05:31:55 pm
Quote
Taking anti-inflammatory supplements increases SHBG. In fact, more than 2 cups of green tea per day will do it.

They took my SHBG over 90!

It's important to note that this is not true for all men.  I drink anywhere from 3 to 9 cups of green tea per day (over 7g quality raw leaf.)  Zero increase in SHBG.  Zero as in zero-zero and not even slight.

If the anti-inflammatory supplement advice were true, all of the high anti-inflammatory supplement takers (say, a majority of the hair loss treament community & the entire anti-aging community as a whole) would see SHBG elevations, and yet they do not.

As far as green tea studies that track SHBG, most are done in Japan and in women that are post-menopausal or that have PCOS.  In these studies, the SHBG increase tops out at 1%.  For an average 30 nmol/L guy that'd boost him all the way up to... still 30 nmol/L, when rounded down.  If you guy by the ultra-high caffeine intake studies (again, in women, and coffee beats tea), you'd expect up to a 3 nmol/L boost.

I think this effect is exceedingly rare.  About as rare as a healthy male having 90 nmol/L of SHBG in the first place.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 16, 2017, 06:55:01 pm
Quote
Taking anti-inflammatory supplements increases SHBG. In fact, more than 2 cups of green tea per day will do it.

They took my SHBG over 90!

It's important to note that this is not true for all men.  I drink anywhere from 3 to 9 cups of green tea per day (over 7g quality raw leaf.)  Zero increase in SHBG.  Zero as in zero-zero and not even slight.

If the anti-inflammatory supplement advice were true, all of the high anti-inflammatory supplement takers (say, a majority of the hair loss treament community & the entire anti-aging community as a whole) would see SHBG elevations, and yet they do not.

As far as green tea studies that track SHBG, most are done in Japan and in women that are post-menopausal or that have PCOS.  In these studies, the SHBG increase tops out at 1%.  For an average 30 nmol/L guy that'd boost him all the way up to... still 30 nmol/L, when rounded down.  If you guy by the ultra-high caffeine intake studies (again, in women, and coffee beats tea), you'd expect up to a 3 nmol/L boost.

I think this effect is exceedingly rare.  About as rare as a healthy male having 90 nmol/L of SHBG in the first place.
Please allow me to redact my statement to "CAN do it".

I have run tens of thousands of SHBG assays on my patients. Anti-oxidants can indeed elevate SHBG. But its level is a balance between more factors than we will probably ever know.

In my case, it was purely the addition of a very high anti-oxidant regimen which took my SHBG from midrange to 90+. That  really was the only change, other than the fact I had to increase my test cyp weekly dose to compensate for same--and more androgen tends to push SHBG down.

As always, every-body is different. But when guys are always wondering about their SHBG--which is what we want them to do, of course (and maybe their doctors?!)--this is indeed an important point to make.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 16, 2017, 06:58:48 pm
Quote
Taking anti-inflammatory supplements increases SHBG. In fact, more than 2 cups of green tea per day will do it.

They took my SHBG over 90!

It's important to note that this is not true for all men.  I drink anywhere from 3 to 9 cups of green tea per day (over 7g quality raw leaf.)  Zero increase in SHBG.  Zero as in zero-zero and not even slight.

If the anti-inflammatory supplement advice were true, all of the high anti-inflammatory supplement takers (say, a majority of the hair loss treament community & the entire anti-aging community as a whole) would see SHBG elevations, and yet they do not.

As far as green tea studies that track SHBG, most are done in Japan and in women that are post-menopausal or that have PCOS.  In these studies, the SHBG increase tops out at 1%.  For an average 30 nmol/L guy that'd boost him all the way up to... still 30 nmol/L, when rounded down.  If you guy by the ultra-high caffeine intake studies (again, in women, and coffee beats tea), you'd expect up to a 3 nmol/L boost.

I think this effect is exceedingly rare.  About as rare as a healthy male having 90 nmol/L of SHBG in the first place.
The SHBG differences you mention really amount to nothing. It's a tough test to do reliably, so the same sample will vary after different runs through the equipment. And SHBG goes up and down several points throughout the day.

BTW, working out elevates SHBG for a time.
Title: Re: More on How SHBG Really Works
Post by: James on December 16, 2017, 07:16:08 pm
Can you, at some point, provide the regimen? 

Anti-oxidants and lowering inflammation and inflammatory cytokines will increase SHBG, I concur.  Are you actually seeing radical increases like yours as the norm?

It's hard to imagine what mechanism could be at work behind a purely anti-oxidant based tripling(30->90 nmol/L?) of SHBG,
however.  It seems more like to be a very bad liver response to a supplement, or just overdoing supplements altogether and really taxing your liver. Even iron overload will do it, for example. (https://www.ncbi.nlm.nih.gov/pubmed/21646287) 

Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 16, 2017, 07:17:49 pm
Can you, at some point, provide the regimen?   

It's hard to imagine what mechanism could be at work behind a purely anti-oxidant based tripling(30->90 nmol/L?) of SHBG, versus having a very bad liver response to a supplement, or overdoing supplements altogether.  A struggling liver often responds with those kinds of outputs.
Do you mean my personal supplement list?
Title: Re: More on How SHBG Really Works
Post by: James on December 16, 2017, 07:26:27 pm
Not an exhaustive one, per se, but yes.  I'm interested in the the anti-oxidant components that are responsible for your increase in SHBG.

Assuming the spike was due to anti-oxidants alone, and it's actually a positive side effect, (a happier, healthier liver) vs. the result of an overtaxed liver (my vote), then it would benefit many men here!
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 17, 2017, 01:01:11 pm
Not an exhaustive one, per se, but yes.  I'm interested in the the anti-oxidant components that are responsible for your increase in SHBG.

Assuming the spike was due to anti-oxidants alone, and it's actually a positive side effect, (a happier, healthier liver) vs. the result of an overtaxed liver (my vote), then it would benefit many men here!
Well said.
Title: Re: More on How SHBG Really Works
Post by: vvs1 on December 17, 2017, 02:43:07 pm
In thinking about this more, my recollection it is actually INFLAMMATION that decreases SHBG, rather than insulin per se.

Again, there is no practical way to alter SHBG.

Interesting comment.  Notice that this study concludes insulin is the prime driver.  However, inflammation falls with weight loss as well - not just insulin - something they don't appear to account for or measure in this study.  However, insulin has been shown in vitro to stimulate SHBG and so these researchers conclude it is an independent stimulator:

https://www.ncbi.nlm.nih.gov/pubmed/7962291

"It is known that there is an inverse relationship between the serum levels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported...During weight loss, insulin levels decreased at an average rate of 6.1 microU/mL per unit decrease in BMI, a much higher slope than the positive slope vs. BMI in weight stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the SHBG vs. insulin coordinates in the weight-losing subjects did not differ significantly from those expected from the SHBG vs. insulin equation in weight-stable subjects. The stability of the SHBG-insulin relationship during weight loss despite the profoundly altered relationship of each separate component to BMI strongly suggests a close metabolic link between SHBG and insulin. As SHBG is not known to alter the production or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion that the predictable inverse relationship between serum insulin and SHBG indicates that insulin controls SHBG synthesis in vivo."
Taking anti-inflammatory supplements increases SHBG. In fact, more than 2 cups of green tea per day will do it.

They took my SHBG over 90!

Did the green tea experiment have any change on estradiol or DHT?
Title: Re: More on How SHBG Really Works
Post by: Oldbull on December 17, 2017, 08:56:14 pm
Serms raise my SHBG but i dont notice any difference when its 15 versus 18.

I dont think someone with genetically low SHBG can do anything to raise that.
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 18, 2017, 10:01:17 am
Quote
Taking anti-inflammatory supplements increases SHBG. In fact, more than 2 cups of green tea per day will do it.

They took my SHBG over 90!

It's important to note that this is not true for all men.  I drink anywhere from 3 to 9 cups of green tea per day (over 7g quality raw leaf.)  Zero increase in SHBG.  Zero as in zero-zero and not even slight.

If the anti-inflammatory supplement advice were true, all of the high anti-inflammatory supplement takers (say, a majority of the hair loss treament community & the entire anti-aging community as a whole) would see SHBG elevations, and yet they do not.

As far as green tea studies that track SHBG, most are done in Japan and in women that are post-menopausal or that have PCOS.  In these studies, the SHBG increase tops out at 1%.  For an average 30 nmol/L guy that'd boost him all the way up to... still 30 nmol/L, when rounded down.  If you guy by the ultra-high caffeine intake studies (again, in women, and coffee beats tea), you'd expect up to a 3 nmol/L boost.

I think this effect is exceedingly rare.  About as rare as a healthy male having 90 nmol/L of SHBG in the first place.
Please allow me to redact my statement to "CAN do it".

I have run tens of thousands of SHBG assays on my patients. Anti-oxidants can indeed elevate SHBG. But its level is a balance between more factors than we will probably ever know.

In my case, it was purely the addition of a very high anti-oxidant regimen which took my SHBG from midrange to 90+. That  really was the only change, other than the fact I had to increase my test cyp weekly dose to compensate for same--and more androgen tends to push SHBG down.

As always, every-body is different. But when guys are always wondering about their SHBG--which is what we want them to do, of course (and maybe their doctors?!)--this is indeed an important point to make.

Okay, this is interesting and the subject of some controversy.  And I have no idea what you were taking, but here is why your story is interesting:

Example, green tea appears to protect against liver cancer:

http://www.tandfonline.com/doi/abs/10.1080/01635581.2017.1263754?journalCode=hnuc20

However, there are a couple of studies showing that green tea extract, which will have a much higher antioxidant profile than green tea of course, can increase the risk of liver issues:

https://www.shape.com/blogs/shape-your-life/when-green-tea-bad-thing

Why?  If you look at study #7 here, you'll see a study that shows that EGCG will cause a dose dependent decrease in glutathione, which is obviously ground zero for the liver.

http://www.peaktestosterone.com/Antioxidant_Dangers.aspx

Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 18, 2017, 05:15:49 pm
Serms raise my SHBG but i dont notice any difference when its 15 versus 18.

I dont think someone with genetically low SHBG can do anything to raise that.
The estrogenic half of a SERM drug sure can elevate SHBG.

...but, from a laboratory testing standpoint, 15 and 18 really  are the same thing.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 18, 2017, 05:20:06 pm
Quote
Taking anti-inflammatory supplements increases SHBG. In fact, more than 2 cups of green tea per day will do it.

They took my SHBG over 90!

It's important to note that this is not true for all men.  I drink anywhere from 3 to 9 cups of green tea per day (over 7g quality raw leaf.)  Zero increase in SHBG.  Zero as in zero-zero and not even slight.

If the anti-inflammatory supplement advice were true, all of the high anti-inflammatory supplement takers (say, a majority of the hair loss treament community & the entire anti-aging community as a whole) would see SHBG elevations, and yet they do not.

As far as green tea studies that track SHBG, most are done in Japan and in women that are post-menopausal or that have PCOS.  In these studies, the SHBG increase tops out at 1%.  For an average 30 nmol/L guy that'd boost him all the way up to... still 30 nmol/L, when rounded down.  If you guy by the ultra-high caffeine intake studies (again, in women, and coffee beats tea), you'd expect up to a 3 nmol/L boost.

I think this effect is exceedingly rare.  About as rare as a healthy male having 90 nmol/L of SHBG in the first place.
Please allow me to redact my statement to "CAN do it".

I have run tens of thousands of SHBG assays on my patients. Anti-oxidants can indeed elevate SHBG. But its level is a balance between more factors than we will probably ever know.

In my case, it was purely the addition of a very high anti-oxidant regimen which took my SHBG from midrange to 90+. That  really was the only change, other than the fact I had to increase my test cyp weekly dose to compensate for same--and more androgen tends to push SHBG down.

As always, every-body is different. But when guys are always wondering about their SHBG--which is what we want them to do, of course (and maybe their doctors?!)--this is indeed an important point to make.

Okay, this is interesting and the subject of some controversy.  And I have no idea what you were taking, but here is why your story is interesting:

Example, green tea appears to protect against liver cancer:

http://www.tandfonline.com/doi/abs/10.1080/01635581.2017.1263754?journalCode=hnuc20

However, there are a couple of studies showing that green tea extract, which will have a much higher antioxidant profile than green tea of course, can increase the risk of liver issues:

https://www.shape.com/blogs/shape-your-life/when-green-tea-bad-thing

Why?  If you look at study #7 here, you'll see a study that shows that EGCG will cause a dose dependent decrease in glutathione, which is obviously ground zero for the liver.

http://www.peaktestosterone.com/Antioxidant_Dangers.aspx
Great example of the quantum nature of life.

...and why  we take things on balance.
Title: Re: More on How SHBG Really Works
Post by: SHBetaG on December 19, 2017, 12:12:48 am
...but, from a laboratory testing standpoint, 15 and 18 really  are the same thing.

Huh, I've been really consistent with my SHBG: 13, 12, 10, 10, 10, 11.

BTW, how is SHBG supposed to fluctuate throughout the day? Doesn't it have a pretty long half-life? Can the liver just produce massive amounts of it suddenly? And can it somehow be eliminated fast? Am I missing something?
Title: Re: More on How SHBG Really Works
Post by: HRT Guru on December 19, 2017, 07:29:54 am
...but, from a laboratory testing standpoint, 15 and 18 really  are the same thing.

Huh, I've been really consistent with my SHBG: 13, 12, 10, 10, 10, 11.

BTW, how is SHBG supposed to fluctuate throughout the day? Doesn't it have a pretty long half-life? Can the liver just produce massive amounts of it suddenly? And can it somehow be eliminated fast? Am I missing something?

The Dr is stating that and SHBG of 15 or 18 are statistically the same reading in response to the person that thought he'd feel something good, or bad, between the two.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 19, 2017, 12:34:48 pm
...but, from a laboratory testing standpoint, 15 and 18 really  are the same thing.

Huh, I've been really consistent with my SHBG: 13, 12, 10, 10, 10, 11.

BTW, how is SHBG supposed to fluctuate throughout the day? Doesn't it have a pretty long half-life? Can the liver just produce massive amounts of it suddenly? And can it somehow be eliminated fast? Am I missing something?

The Dr is stating that and SHBG of 15 or 18 are statistically the same reading in response to the person that thought he'd feel something good, or bad, between the two.
yes, sir.

I have seen the same blood sample run twice, at the same lab, at the same time, and report back 10 points from each other. SHBG appears to be a difficult assay to run consistently.
Title: Re: More on How SHBG Really Works
Post by: SHBetaG on December 19, 2017, 10:00:21 pm
And SHBG goes up and down several points throughout the day.

BTW, how is SHBG supposed to fluctuate throughout the day? Doesn't it have a pretty long half-life? Can the liver just produce massive amounts of it suddenly? And can it somehow be eliminated fast? Am I missing something?

I have seen the same blood sample run twice, at the same lab, at the same time, and report back 10 points from each other. SHBG appears to be a difficult assay to run consistently.


Huh, it's weird then that many low SHBG guys report that their SHBG tends to not fluctuate much at all (like in my case)..
Title: Re: More on How SHBG Really Works
Post by: HRT Guru on December 20, 2017, 09:04:23 am
And SHBG goes up and down several points throughout the day.

BTW, how is SHBG supposed to fluctuate throughout the day? Doesn't it have a pretty long half-life? Can the liver just produce massive amounts of it suddenly? And can it somehow be eliminated fast? Am I missing something?

I have seen the same blood sample run twice, at the same lab, at the same time, and report back 10 points from each other. SHBG appears to be a difficult assay to run consistently.


Huh, it's weird then that many low SHBG guys report that their SHBG tends to not fluctuate much at all (like in my case)..

What youre reaching for and what Dr C stated really aren't the same thing.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 20, 2017, 10:22:27 am
And SHBG goes up and down several points throughout the day.

BTW, how is SHBG supposed to fluctuate throughout the day? Doesn't it have a pretty long half-life? Can the liver just produce massive amounts of it suddenly? And can it somehow be eliminated fast? Am I missing something?

I have seen the same blood sample run twice, at the same lab, at the same time, and report back 10 points from each other. SHBG appears to be a difficult assay to run consistently.
We would expect that.

Even if for the simple reason a...say...10% variation means wider swings at 80 than it does 8.

Huh, it's weird then that many low SHBG guys report that their SHBG tends to not fluctuate much at all (like in my case)..
Title: Re: More on How SHBG Really Works
Post by: Gef on December 21, 2017, 04:57:31 am
I want to share my Danazol experience with other members. I am not on TRT.  I tried Danazol 50mg daily for 1 month to lower my SHBG in the hope of reviving my libido. Everything else was in the normal range. The following are my recent lab results before Danazol, 11/06/17 and after 12/13/17.
Total testosterone: 660 ng/dL  ->  337 ng/dL     
Free Testosterone (Direct)   7.6 pg/mL  -  High >50.0 pg/mL
Estradiol   27.1 pg/mL -  35.2 pg/mL     
DHEA-Sulfate  202.9 ug/dL - 251.2 ug/dL   
Dihydrotestosterone  75 ng/dL – 50 ng/dL
SHBG          111.7 nmol/L  – 73.9 nmol/L

Title: Re: More on How SHBG Really Works
Post by: Cataceous on December 21, 2017, 06:13:19 am
Thanks for sharing these interesting results. Any side effects from the medication? What are subjective results--any change in libido?

Contradicting directly-measured free testosterone, calculated free testosterone dropped from 5.4 ng/dL (0.8%) to 3.8 ng/dL (1.1%), suggesting no improvement.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 23, 2017, 05:37:58 pm
I want to share my Danazol experience with other members. I am not on TRT.  I tried Danazol 50mg daily for 1 month to lower my SHBG in the hope of reviving my libido. Everything else was in the normal range. The following are my recent lab results before Danazol, 11/06/17 and after 12/13/17.
Total testosterone: 660 ng/dL  ->  337 ng/dL     
Free Testosterone (Direct)   7.6 pg/mL  -  High >50.0 pg/mL
Estradiol   27.1 pg/mL -  35.2 pg/mL     
DHEA-Sulfate  202.9 ug/dL - 251.2 ug/dL   
Dihydrotestosterone  75 ng/dL – 50 ng/dL
SHBG          111.7 nmol/L  – 73.9 nmol/L
But how did it make you feel?
Title: Re: More on How SHBG Really Works
Post by: PeakT on December 26, 2017, 11:40:43 am
I want to share my Danazol experience with other members. I am not on TRT.  I tried Danazol 50mg daily for 1 month to lower my SHBG in the hope of reviving my libido. Everything else was in the normal range. The following are my recent lab results before Danazol, 11/06/17 and after 12/13/17.
Total testosterone: 660 ng/dL  ->  337 ng/dL     
Free Testosterone (Direct)   7.6 pg/mL  -  High >50.0 pg/mL
Estradiol   27.1 pg/mL -  35.2 pg/mL     
DHEA-Sulfate  202.9 ug/dL - 251.2 ug/dL   
Dihydrotestosterone  75 ng/dL – 50 ng/dL
SHBG          111.7 nmol/L  – 73.9 nmol/L

Can you post a separate thread on this?  I'd love to ask  you some questions, but this will end up buried in this thread.
Title: Re: More on How SHBG Really Works
Post by: ratbag on December 26, 2017, 02:54:38 pm
The link in the first post isn`t working.
Title: Re: More on How SHBG Really Works
Post by: Mindscape on December 26, 2017, 03:34:10 pm
The link in the first post isn`t working.

It never worked for me either.
Title: Re: More on How SHBG Really Works
Post by: Cataceous on December 26, 2017, 06:39:40 pm
The link in the first post isn`t working.

Seems to have been missing an "s". I will fix it in the original.

http://drjohncrisler.com/how-sex-hormone-binding-globulin-shbg-really-works.html
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 26, 2017, 07:30:35 pm
The link in the first post isn`t working.

Seems to have been missing an "s". I will fix it in the original.

http://drjohncrisler.com/how-sex-hormone-binding-globulin-shbg-really-works.html
Thank you.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 26, 2017, 07:32:16 pm
I think this binding of Free SHBG to its own receptor on the cell membrane is going to turn out to be a really big deal.
Title: Re: More on How SHBG Really Works
Post by: Gef on December 26, 2017, 11:44:22 pm
Thanks for sharing these interesting results. Any side effects from the medication? What are subjective results--any change in libido?

Contradicting directly-measured free testosterone, calculated free testosterone dropped from 5.4 ng/dL (0.8%) to 3.8 ng/dL (1.1%), suggesting no improvement.

There were no side effects at all, it made no difference in how I felt in general or my libido.
Title: Re: More on How SHBG Really Works
Post by: Gef on December 27, 2017, 12:02:17 am
I want to share my Danazol experience with other members. I am not on TRT.  I tried Danazol 50mg daily for 1 month to lower my SHBG in the hope of reviving my libido. Everything else was in the normal range. The following are my recent lab results before Danazol, 11/06/17 and after 12/13/17.
Total testosterone: 660 ng/dL  ->  337 ng/dL     
Free Testosterone (Direct)   7.6 pg/mL  -  High >50.0 pg/mL
Estradiol   27.1 pg/mL -  35.2 pg/mL     
DHEA-Sulfate  202.9 ug/dL - 251.2 ug/dL   
Dihydrotestosterone  75 ng/dL – 50 ng/dL
SHBG          111.7 nmol/L  – 73.9 nmol/L
But how did it make you feel?

It made no difference on how I felt even though my SHBG level dropped significantly. I stopped taking it after I learned that it could adversely effect my HPTA levels.
Title: Re: More on How SHBG Really Works
Post by: Gef on December 27, 2017, 12:14:32 am


Can you post a separate thread on this?  I'd love to ask  you some questions, but this will end up buried in this thread.
[/quote]

I have posted a new separate thread on this under "My Danazol experience"
Title: Re: More on How SHBG Really Works
Post by: Dr Justin Saya, MD on December 27, 2017, 12:16:26 am
I want to share my Danazol experience with other members. I am not on TRT.  I tried Danazol 50mg daily for 1 month to lower my SHBG in the hope of reviving my libido. Everything else was in the normal range. The following are my recent lab results before Danazol, 11/06/17 and after 12/13/17.
Total testosterone: 660 ng/dL  ->  337 ng/dL     
Free Testosterone (Direct)   7.6 pg/mL  -  High >50.0 pg/mL
Estradiol   27.1 pg/mL -  35.2 pg/mL     
DHEA-Sulfate  202.9 ug/dL - 251.2 ug/dL   
Dihydrotestosterone  75 ng/dL – 50 ng/dL
SHBG          111.7 nmol/L  – 73.9 nmol/L
But how did it make you feel?

It made no difference on how I felt even though my SHBG level dropped significantly. I stopped taking it after I learned that it could adversely effect my HPTA levels.

For those that don't already know, a public service announcement: do NOT take Danazol unless your HPTA is already suppressed (e.g. do not take it if you are NOT on TRT)...it will suppress your HPTA.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 27, 2017, 03:44:14 am
I want to share my Danazol experience with other members. I am not on TRT.  I tried Danazol 50mg daily for 1 month to lower my SHBG in the hope of reviving my libido. Everything else was in the normal range. The following are my recent lab results before Danazol, 11/06/17 and after 12/13/17.
Total testosterone: 660 ng/dL  ->  337 ng/dL     
Free Testosterone (Direct)   7.6 pg/mL  -  High >50.0 pg/mL
Estradiol   27.1 pg/mL -  35.2 pg/mL     
DHEA-Sulfate  202.9 ug/dL - 251.2 ug/dL   
Dihydrotestosterone  75 ng/dL – 50 ng/dL
SHBG          111.7 nmol/L  – 73.9 nmol/L
But how did it make you feel?

It made no difference on how I felt even though my SHBG level dropped significantly. I stopped taking it after I learned that it could adversely effect my HPTA levels.
That was the same experience of a number of patients who tried this.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on December 27, 2017, 03:47:55 am
I want to share my Danazol experience with other members. I am not on TRT.  I tried Danazol 50mg daily for 1 month to lower my SHBG in the hope of reviving my libido. Everything else was in the normal range. The following are my recent lab results before Danazol, 11/06/17 and after 12/13/17.
Total testosterone: 660 ng/dL  ->  337 ng/dL     
Free Testosterone (Direct)   7.6 pg/mL  -  High >50.0 pg/mL
Estradiol   27.1 pg/mL -  35.2 pg/mL     
DHEA-Sulfate  202.9 ug/dL - 251.2 ug/dL   
Dihydrotestosterone  75 ng/dL – 50 ng/dL
SHBG          111.7 nmol/L  – 73.9 nmol/L
But how did it make you feel?

It made no difference on how I felt even though my SHBG level dropped significantly. I stopped taking it after I learned that it could adversely effect my HPTA levels.

For those that don't already know, a public service announcement: do NOT take Danazol unless your HPTA is already suppressed (e.g. do not take it if you are NOT on TRT)...it will suppress your HPTA.
There is debate about whether this is direct suppression at the hypothalamus/pituitary, through negative feedback on LH levels, or both.

At any rate, it doesn't work.

Neither do SHBG lowering supplements (long term)....due to negative feedback subsequently lowering LH.
Title: Re: More on How SHBG Really Works
Post by: James on January 06, 2018, 06:18:38 am
Serms raise my SHBG but i dont notice any difference when its 15 versus 18.

I dont think someone with genetically low SHBG can do anything to raise that.
The estrogenic half of a SERM drug sure can elevate SHBG.

...but, from a laboratory testing standpoint, 15 and 18 really  are the same thing.

It won't where SHBG expression is genetically deficient, as Oldbull posits. If the liver doesn't respond properly to estradiol, it won't respond any better to a weak, tissue specific estrogen agonist like the clomiphene isomer zuclomiphene.

Moreover, the claim that clomiphene (assuming that this is the referenced SERM) increases estradiol is contentious.  In the oft referenced study where clomiphene "increases" SHBG from an average of 38 to 54 nmol/L, the careful reader notes that the researchers conclude that the SHBG increase was probably due to the concomitant increase in serum estradiol, and not to a more direct action of clomiphene.  In this same study, E2 increased from ~24 to ~43 pg/mL, for example.
[https://www.ncbi.nlm.nih.gov/m/pubmed/6797955/]

There is a more promising compound being studied.  It's a selective estrogen receptor agonist with a 10-fold preference for activation of ERα relative to ERβ.  This can send SHBG into the stratosphere in eugonadal men, and therefore I suspect it may hold promise, in small doses, for those men who suffer from SHBG not being naturally expressed in adequate proportion to their hormones.

Any thought given to revealing the antioxidant regimen that tripled your SHBG output?  I still believe you've just gummed up your liver with too many supplements, but if you've actually managed to accidentally overstimulate SHBG to an unheard of degree, it's worth breaking apart the regimen to find the components responsible.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on January 06, 2018, 05:46:54 pm
Serms raise my SHBG but i dont notice any difference when its 15 versus 18.

I dont think someone with genetically low SHBG can do anything to raise that.
The estrogenic half of a SERM drug sure can elevate SHBG.

...but, from a laboratory testing standpoint, 15 and 18 really  are the same thing.
I have seen Clomiphene elevate SHBG numerous times.

I've seen adding an AI, to lower estrogen, lower SHBG hundreds of times.

Good point about the low SHBG, and being stuck with it! Low SHBG can be a real stinker. For those who also need thyroid therapy, that can elevate SHBG.

I take fish oil, curcurmin, lots of veggies, etc. The curcurmin was added after the MI, but I don't know if we can credit that. As I always say,

It won't where SHBG expression is genetically deficient, as Oldbull posits. If the liver doesn't respond properly to estradiol, it won't respond any better to a weak, tissue specific estrogen agonist like the clomiphene isomer zuclomiphene.

Moreover, the claim that clomiphene (assuming that this is the referenced SERM) increases estradiol is contentious.  In the oft referenced study where clomiphene "increases" SHBG from an average of 38 to 54 nmol/L, the careful reader notes that the researchers conclude that the SHBG increase was probably due to the concomitant increase in serum estradiol, and not to a more direct action of clomiphene.  In this same study, E2 increased from ~24 to ~43 pg/mL, for example.
[https://www.ncbi.nlm.nih.gov/m/pubmed/6797955/]

There is a more promising compound being studied.  It's a selective estrogen receptor agonist with a 10-fold preference for activation of ERα relative to ERβ.  This can send SHBG into the stratosphere in eugonadal men, and therefore I suspect it may hold promise, in small doses, for those men who suffer from SHBG not being naturally expressed in adequate proportion to their hormones.

Any thought given to revealing the antioxidant regimen that tripled your SHBG output?  I still believe you've just gummed up your liver with too many supplements, but if you've actually managed to accidentally overstimulate SHBG to an unheard of degree, it's worth breaking apart the regimen to find the components responsible.
Title: Re: More on How SHBG Really Works
Post by: Dr. John Crisler on January 06, 2018, 05:50:44 pm
Serms raise my SHBG but i dont notice any difference when its 15 versus 18.

I dont think someone with genetically low SHBG can do anything to raise that.
The estrogenic half of a SERM drug sure can elevate SHBG.

...but, from a laboratory testing standpoint, 15 and 18 really  are the same thing.

It won't where SHBG expression is genetically deficient, as Oldbull posits. If the liver doesn't respond properly to estradiol, it won't respond any better to a weak, tissue specific estrogen agonist like the clomiphene isomer zuclomiphene.

Moreover, the claim that clomiphene (assuming that this is the referenced SERM) increases estradiol is contentious.  In the oft referenced study where clomiphene "increases" SHBG from an average of 38 to 54 nmol/L, the careful reader notes that the researchers conclude that the SHBG increase was probably due to the concomitant increase in serum estradiol, and not to a more direct action of clomiphene.  In this same study, E2 increased from ~24 to ~43 pg/mL, for example.
[https://www.ncbi.nlm.nih.gov/m/pubmed/6797955/]

There is a more promising compound being studied.  It's a selective estrogen receptor agonist with a 10-fold preference for activation of ERα relative to ERβ.  This can send SHBG into the stratosphere in eugonadal men, and therefore I suspect it may hold promise, in small doses, for those men who suffer from SHBG not being naturally expressed in adequate proportion to their hormones.

Any thought given to revealing the antioxidant regimen that tripled your SHBG output?  I still believe you've just gummed up your liver with too many supplements, but if you've actually managed to accidentally overstimulate SHBG to an unheard of degree, it's worth breaking apart the regimen to find the components responsible.
Sorry about the previous post; I wasn't careful in placing the cursor. here's my response to your good post, James:
 I have seen Clomiphene elevate SHBG numerous times.

I've seen adding an AI, to lower estrogen, lower SHBG hundreds of times.

Good point about the low SHBG, and being stuck with it. Low SHBG can be a real stinker, and nothing seems to move it. If it is at 15, and it goes to 20, that would still be within the wobble we see in that particular assay. Even though it would be a 1/3rd increase. But going the same 1/3rd from 45 to 60 sure would make a difference. Just some things to think about.

For those who also need thyroid therapy, that can elevate SHBG.

I've given liver health a lot of thought, as you point out. I also take milk thistle twice per day, and also NAC. Not much alcohol, and the same for refined sugars.

I hadn't heard about the new ER agonist, until reading your post.