Blocking Androgen Receptors in the Hypothalamus?

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keigwin

Member
I’ve been doing a little reading about the HPTA, as I’ve been considering TRT and want to understand what it really does. This led me to a (perhaps stupid) question.


It seems that standard practice is to use HCG in addition to supplemental testosterone if one wants to preserve his natural ability to produce testosterone. But HCG doesn’t really deal with the root of the problem, i.e. that when you supplement your testosterone, the hypothalamus detects excess androgens and shuts down the hormone chain that leads your testicles to produce T. It just provides a substitute for one of the products from halfway down the chain (LH). It seems the ideal would be to block the androgen receptors in the hypothalamus so that it doesn’t detect the excess T in the first place, thus preserving the normal operation of the HPTA. Is there nothing that can do this?
 
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CoastWatcher

Moderator
I've been doing a little reading about the HPTA, as I've been considering TRT and want to understand what it really does. This led me to a (perhaps stupid) question.


It seems that standard practice is to use HCG in addition to supplemental testosterone if one wants to preserve his natural ability to produce testosterone. But HCG doesn't really deal with the root of the problem, i.e. that when you supplement your testosterone, the hypothalamus detects excess androgens and shuts down the hormone chain that leads your testicles to produce T. It just provides a substitute for one of the products from halfway down the chain (LH). It seems the ideal would be to block the androgen receptors in the hypothalamus so that it doesn't detect the excess T in the first place, thus preserving the normal operation of the HPTA. Is there nothing that can do this?

No, there is not.
 
I’ve been doing a little reading about the HPTA, as I’ve been considering TRT and want to understand what it really does. This led me to a (perhaps stupid) question.


It seems that standard practice is to use HCG in addition to supplemental testosterone if one wants to preserve his natural ability to produce testosterone. But HCG doesn’t really deal with the root of the problem, i.e. that when you supplement your testosterone, the hypothalamus detects excess androgens and shuts down the hormone chain that leads your testicles to produce T. It just provides a substitute for one of the products from halfway down the chain (LH). It seems the ideal would be to block the androgen receptors in the hypothalamus so that it doesn’t detect the excess T in the first place, thus preserving the normal operation of the HPTA. Is there nothing that can do this?

Clomid blocks E2 from binding to receptors in the hypothalamus and pituitary, but it does NOT overcome the suppression of TRT.

Plus, anything that blocks androgen receptors in the brain will also probably block the benefits of TRT.
 

keigwin

Member
I inject 500iu of HCG every 3 1/2 days along with my testosterone, mainly to keep my testicle size.
Nelson has a good thread on the subject.
The Use of HCG to Prevent / Reverse Testicular Shrinkage and Preserve Fertility
https://www.excelmale.com/showthread...erve-Fertility
Thanks, but that's not really what I was asking. I want to know if there's a better alternative to HCG that stops the hypothalamus from detecting the testosterone supplementation of TRT.
 

keigwin

Member
Clomid blocks E2 from binding to receptors in the hypothalamus and pituitary, but it does NOT overcome the suppression of TRT.

Plus, anything that blocks androgen receptors in the brain will also probably block the benefits of TRT.

And this is the trick, isn't it? It would have to be a selective AR blocker targeting only androgens in the hypothalamus (or perhaps the pituitary as well). Too bad if it doesn't exist yet. Sounds like it would be the holy grail of TRT.
 

madman

Super Moderator
And this is the trick, isn't it? It would have to be a selective AR blocker targeting only androgens in the hypothalamus (or perhaps the pituitary as well). Too bad if it doesn't exist yet. Sounds like it would be the holy grail of TRT.

Androgen receptors are critical as the biological actions of androgens are mediated through the AR and even if one could specifically target blocking AR in (hypo/pit) it would prove to be detrimental as not only does the AR play an important role in the development/maintenance of the reproductive , musculoskeletal, cardiovascular, immune, and haemopoietic systems but also the NEURAL system. Links to articles may be a dry read but alteast it will give you some insight to the importance of the AR.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2096617/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810760/
 
And this is the trick, isn't it? It would have to be a selective AR blocker targeting only androgens in the hypothalamus (or perhaps the pituitary as well). Too bad if it doesn't exist yet. Sounds like it would be the holy grail of TRT.

I don't see how it'd be better than just using hCG. It's an interesting theoretical thought but has little clinical benefit over just using hCG, which is an LH receptor agonist achieving the same result as endogenous LH.

Keep in mind the androgen receptor isn't even suspected to be totally responsible for the suppressive actions of exogenous testosterone, estrogen receptors are. We already have those, they're called SERMs and they do not work with TRT.
 

keigwin

Member
Androgen receptors are critical as the biological actions of androgens are mediated through the AR and even if one could specifically target blocking AR in (hypo/pit) it would prove to be detrimental as not only does the AR play an important role in the development/maintenance of the reproductive , musculoskeletal, cardiovascular, immune, and haemopoietic systems but also the NEURAL system. Links to articles may be a dry read but alteast it will give you some insight to the importance of the AR.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2096617/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810760/

Yes, a dry read to be sure, but information that looks to be helpful. Thanks for the links.

Really what I'm hypothesizing isn't so much a complete blocking of AR action as it is a reduction in it so as to make it "look" to the HPT axis as if your testosterone levels are flat, despite the fact that you're dosing with exogenous T.
 
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