Effect of TRT vs hCG/FSH on upstream hormone pathways.

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What we see is that with hCG serum estradiol is 0.65% of total testosterone versus 0.45% for TRT versus 0.46% for controls. This supports the idea of hCG upsetting the balance of estradiol.
Or "enhancing" instead of upsetting.

If you look at intratesticular testosterone, it was highest in hCG+FSH. This variable is the most important one along with 17-OH progesterone in predicting healthy sperm count/quality.
 
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@madman

I only like it since it represents a challenge to educate men about dogma they learned during years of wrong online information. More and more researchers are validating the view that estradiol is actually an enhancer of testosterone action and that it only becomes an issue in the presence of low T or even high IGF-1.


 
What we see is that with hCG serum estradiol is 0.65% of total testosterone versus 0.45% for TRT versus 0.46% for controls. This supports the idea of hCG upsetting the balance of estradiol.

Something we always knew anecdotally and the reason probably why the vast majority of us never felt good on HCG. With AI or no AI I never managed to get dialed in with HCG.
With T only there's no issue, since E2 follows T and the ratio is the same.

Dr. Jordan Grant mentioned it often in his videos, that he rarely sees patients doing good on HCG long term, due to the offset in the ratio. He's a great advocate of inject T only and let your body do its job, aromatizing as much as needed. No advice was better than that for many of us.
 
Something we always knew anecdotally and the reason probably why the vast majority of us never felt good on HCG. With AI or no AI I never managed to get dialed in with HCG.
With T only there's no issue, since E2 follows T and the ratio is the same.

Dr. Jordan Grant mentioned it often in his videos, that he rarely sees patients doing good on HCG long term, due to the offset in the ratio. He's a great advocate of inject T only and let your body do its job, aromatizing as much as needed. No advice was better than that for many of us.
that's not really a huge jump in e2.
 
It is likely that the E2:T ratio has importance that is independent of the absolute levels of the hormones. If this is the case then it must be considered pretty significant for hCG to increase the ratio by 44%.
Are you an HCG user if so how do you manage your side effects if any?
 
Are you an HCG user if so how do you manage your side effects if any?
I'm a former hCG user. I did well for a while with it, but in the end it was too difficult to manage the side effects, so I switched to gonadorelin. Even low doses of hCG would increase my estradiol by ~20 pg/mL, which in turn raised prolactin over time. These could be attacked with anastrozole and/or cabergoline, but they complicate the protocol and may have their own side effects, and in the end the results were still subpar.
 
I speak about the potential effect of hCG on upstream hormones here:

Thank you very much Nelson for posting this! I've been very confused about the use of hCG along with TRT. Your presentation was informative as it was educational. The key take away for me is the potential effects on upstream hormones - something l never thought about until I seen your presentation. Thanks again and stay safe.
 
Even low doses of hCG would increase my estradiol by ~20 pg/mL, which in turn raised prolactin over time.

Did you ever do a pituitary gland MRI to check for a prolactinoma?
I though that was the case with me as well, as the more I was increasing my T dose, the higher prolactin was going, so I was blaming it on E2. Then I realised through several blood tests that prolactin levels weren't correlated with AIs usage and E2 levels and I did an MRI.
Turned out I was having a prolactinoma.
 
Did you ever do a pituitary gland MRI to check for a prolactinoma?
I though that was the case with me as well, as the more I was increasing my T dose, the higher prolactin was going, so I was blaming it on E2. Then I realised through several blood tests that prolactin levels weren't correlated with AIs usage and E2 levels and I did an MRI.
Turned out I was having a prolactinoma.
I had an MRI around when I started TRT and it was normal, though that was a few years back. I won't claim a perfect correlation between estradiol and prolactin, but I think if I have a prolactinoma then the symptoms would not have resolved so readily with a protocol change. I was able to stop taking cabergoline, though it's possible the low doses of selegiline I now take are also lowering prolactin a little.
 
I had it around 20 for several years, way before TRT. Then when I went above 100 mg per week of T, it went to 40 and then almost to 60, so I decided to have an MRI.
It was probably there already since years and got bigger on TRT.

I'll see if it shrinks in one year of treatment with 0.75 mg of cabergoline per week, otherwise I'll remove the prolactinoma surgically. I feel quite fatigued after few months at this dose and I started having brain fog.
 
Figure 3 -Serum steroid hormone concentrations from Δ5 and Δ4 pathways of CHH males (including testosterone metabolites) analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), once, while patients were undergoing hCG/rFSH treatment and again, while they were on T replacement, compared to those of healthy matched controls.
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We can see that TRT actually decreases cortisol, at least in this study.

TRT cortisol.jpg
 
We can see that TRT actually decreases cortisol, at least in this study.

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I always wondered if TRT reduced cortisol. I think that's why it has such a calming effect on me and reduces anxiety so well. Also, after a hard workout before I was on TRT, I'd feel anxious and I thought it was due to the cortisol spike. It makes sense now. These days I can workout super hard and never have that anxious type feeling.
 
Excuse me in advance for reading over all this a bit quickly and not being the most scientifically minded person in the world, but does this then show that HCG does not elevate all of the hormones like progesterone, and additional supplementation would be needed for those? And if so, should these hormones actually be replaced? Are they needed while on TRT or does the demand for these hormones decrease?
 
Excuse me in advance for reading over all this a bit quickly and not being the most scientifically minded person in the world, but does this then show that HCG does not elevate all of the hormones like progesterone, and additional supplementation would be needed for those? And if so, should these hormones actually be replaced? Are they needed while on TRT or does the demand for these hormones decrease?
Your question is interesting. The replacement of these hormones like progesterone I believe would be necessary
 
Excuse me in advance for reading over all this a bit quickly and not being the most scientifically minded person in the world, but does this then show that HCG does not elevate all of the hormones like progesterone, and additional supplementation would be needed for those? And if so, should these hormones actually be replaced? Are they needed while on TRT or does the demand for these hormones decrease?
I'm also going to vote in favor of replacement. If, for example, you read the Wiki entry for DHEA, you find that it's doing a great deal more than just being a hormone precursor. "However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and modulator of neurotrophic factor receptors."

In the absence of better information, if replacement is attempted then I think it's safer not to have serum levels exceed mid-range for young males. These things tend to have U-shaped mortality curves, so why push your luck?
 
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I'm also going to vote in favor of replacement. If, for example, you read the Wiki entry for DHEA, you find that it's doing a great deal more than just being a hormone precursor. "However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and modulator of neurotrophic factor receptors."

In the absence of better information, if replacement is attempted then I think it's safer not to have serum levels exceed mid-range for young males. These things tend to have U-shaped mortality curves, so why push your luck?
My DHEA is mid range, but my progesterone is completely undetectable. Supplementing 30mg pregnenolone raises my progesterone to 0.2, but even 10mg of preg makes me so tired I can't function, and Defy told me not to replace progesterone directly in males. I assumed it had a function, but honestly the information available is so confusing and contradictory that I can't seem to find an answer or anything that works. HCG would be very convenient but I don't think it actually raises downstream hormones, I've never seen that in my labs, and it has its own problems for me like excessive E2.
 
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