More on How SHBG Really Works

[Dr Justin Saya, MD]

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.

[Dr. John Crisler]

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.

[Dr. John Crisler]

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.

[James]

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.

[Dr. John Crisler]

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.

[Dr. John Crisler]

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.