Peak Testosterone Forum

General Category => Testosterone, Hormones and General Men's Health => Topic started by: Cataceous on January 03, 2016, 08:29:25 pm

Title: Split: Pharmacokinetics of hCG with Different Doses and Schedules
Post by: Cataceous on January 03, 2016, 08:29:25 pm
[Mod: Topic split from here (http://www.peaktestosterone.com/forum/index.php?topic=8931.0), with article that's stimulating discussion here: http://jpet.aspetjournals.org/content/289/1/371.full]

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The evidence does not suggest benefits to daily dosing of hCG versus less-frequent dosing. You'd probably be hard-pressed to notice much difference between ed, eod and e3d. The reasons include not just the half life, but also the testosterone response curves. I've personally tried both ed and eod and noticed no difference. As K says, hCG injections are very easy and fast

An interesting study, but the lowest dose they are using is 500IU daily, which is a horse dose. Also, they aren't taking into account the increased estradiol levels produced with larger doses.

That's not quite how it worked. The subjects were given 2500 IU only, as one isolated dose, and then on five consecutive eods. The measured serum data were used to determine the best model for the testosterone production response. Then the model was used to generate response curves for various doses at various intervals. Theoretically you can plug in any dose and interval to see what the typical testosterone response would be. A particularly interesting feature is that dose rates of 500 IU/day or 1000 IU eod seem to maximize production. Higher doses actually reduce production.

I'm not sure what you mean regarding estradiol. In the general sense this study is about testosterone response to hCG, so estradiol isn't relevant. In a specific sense the authors note that estradiol levels increase with hCG levels and that "the present study design does not allow differentiation of the effects of the increase in estradiol or in hCG serum levels." Obviously for those of us on TRT and/or hCG, estradiol levels are important. Because hCG directly stimulates aromatization we should always use the minimum amount of hCG that can do the job. This is more important for those on monotherapy, and this work provides guidance for getting the most testosterone from the least hCG.
Title: Re: Re: Thinking of going HCG Mono.. Or TRT temporarily.. thoughts?
Post by: SumTingWong on January 03, 2016, 09:22:46 pm
I notice you're confused.

My point is that the study only looks at a very limited dosing protocol. You therefore cannot just write off the idea of doing daily dosing, because the study only looked at a limited dosing protocol, with the smallest dose being 500IU.

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so estradiol isn't relevant.

It is relevant to the person taking the HCG. The point of the thread is to help audiognostic.
Title: Re: Re: Thinking of going HCG Mono.. Or TRT temporarily.. thoughts?
Post by: Kierkegaard on January 03, 2016, 10:04:30 pm
Keep going, guys.  Great conversation. 
Title: Re: Re: Thinking of going HCG Mono.. Or TRT temporarily.. thoughts?
Post by: Cataceous on January 04, 2016, 03:56:11 am
I notice you're confused.

My point is that the study only looks at a very limited dosing protocol. You therefore cannot just write off the idea of doing daily dosing, because the study only looked at a limited dosing protocol, with the smallest dose being 500IU.

I notice you don't seem to have read either my post or the study. The study creates a model that should be useful for a wide range of doses and timing, including ed and eod and much lower amounts of hCG. I can write off the idea of daily dosing because it appears that one gets almost the same results with eod and probably even e3d dosing; the steady-state oscillations are not that large.

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so estradiol isn't relevant.

It is relevant to the person taking the HCG. The point of the thread is to help audiognostic.

I direct you to my previous post:

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... Obviously for those of us on TRT and/or hCG, estradiol levels are important. Because hCG directly stimulates aromatization we should always use the minimum amount of hCG that can do the job. This is more important for those on monotherapy, and this work provides guidance for getting the most testosterone from the least hCG.

If it's easier for audiognostic and others to inject their hCG every third day then they should rather than worry about the unsupported idea that more frequent dosing is better. I only do eod myself because an alternating injection of test/hCG every day is an easy habit to keep.
Title: Re: Re: Thinking of going HCG Mono.. Or TRT temporarily.. thoughts?
Post by: Kierkegaard on January 04, 2016, 04:39:57 am
This an excellent study.  The chart here seems to be the meat of it for our discussion:

http://jpet.aspetjournals.org/content/289/1/371/F5.expansion.html

Notice that the daily subq 500 IUs (top left) resulted in the most robust response (working better than higher doses), but the study time (5 shots) didn't really capture at all the power of daily low-level subq injections over time.  It just got to the point of day 5 and (because no more shots were given) trailed off.  What do you think would have happened if this was extended to 10 or 20 shots?  We can't know for sure.  Perhaps the levels would have been even smoother at daily injections than longer schedules. 

Also, what about the effect on estradiol?  I'm assuming hCG stimulates aromatase in the leydig cells, but how?  Is it simply a matter of conversion from T to E2 via aromatase, as with exogenous testosterone?  If that's the case, then why are conversion levels typically higher (say others) when it comes to hCG injections compared to testosterone injections?  If this higher conversion is true, it'd probably be safer to aim for smaller daily injections rather than bigger injections less frequently. 
Title: Re: Split: Pharmacokinetics of hCG with Different Doses and Schedules
Post by: Sighalot on January 04, 2016, 05:08:54 am
A particularly interesting feature is that dose rates of 500 IU/day or 1000 IU eod seem to maximize production. Higher doses actually reduce production.
We have one member that got decent T levels with 3x500 but already at 3x700 T got lower.
Title: Re: Re: Thinking of going HCG Mono.. Or TRT temporarily.. thoughts?
Post by: Hydranted on January 04, 2016, 05:50:13 am
This an excellent study.  The chart here seems to be the meat of it for our discussion:

http://jpet.aspetjournals.org/content/289/1/371/F5.expansion.html

Also, what about the effect on estradiol?  I'm assuming hCG stimulates aromatase in the leydig cells, but how?  Is it simply a matter of conversion from T to E2 via aromatase, as with exogenous testosterone?  If that's the case, then why are conversion levels typically higher (say others) when it comes to hCG injections compared to testosterone injections?  If this higher conversion is true, it'd probably be safer to aim for smaller daily injections rather than bigger injections less frequently.


Although there is still a ton of research to be done on the topic, a logical (to me) explanation for the effects that hCG can have on estradiol levels goes something like this...


-Since hCG is an LH analog, the testes end up receiving a higher-than-normal (and usually a more constant) "LH pulse". 

-The increase in LH leads to an increase of intratesticular testosterone (ITT).  ITT is far more "abundant" than serum testosterone.  After all, the testes are where we naturally produce the hormone.

-In humans, the consensus is that the Leydig cells are the primary source of aromatase activity in the testes.  It is also believed that there is aromatase activity within the Sertoli and germ cells...with some recent research showing that there may be quite a bit more activity there than previously thought.

-If ITT production is kicked into high gear by hCG, it makes sense that the intratesticular aromatase would follow suit.

-Since exogenous testosterone does not stimulate the production of ITT like hCG does (it does the opposite, via HPTA suppression), the bulk of the aromatase that's left to convert T-->E is the stuff that's found in peripheral tissues...or outside of the testes.  This may be why the conversion of T-->E is less pronounced in men solely on testosterone. 

-In men who use testosterone and hCG, both sources of aromatase should technically be available to carry out their duties. 


Don't feel like you have to take the above as gospel, but it definitely makes the most sense to me.
Title: Re: Split: Pharmacokinetics of hCG with Different Doses and Schedules
Post by: Kierkegaard on January 04, 2016, 05:58:47 am
Makes sense to me too.  Great stuff.
Title: Re: Re: Thinking of going HCG Mono.. Or TRT temporarily.. thoughts?
Post by: Cataceous on January 04, 2016, 01:22:30 pm
...
Also, what about the effect on estradiol?  I'm assuming hCG stimulates aromatase in the leydig cells, but how?  Is it simply a matter of conversion from T to E2 via aromatase, as with exogenous testosterone?...

Though done on rats, this study (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC411596/) should be applicable and answer some of your questions.

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... These results demonstrate that purified Leydig cells have a high capacity for aromatization and that hCG can acutely stimulate aromatization independently of stimulating testosterone synthesis in vitro.
Title: Re: Split: Pharmacokinetics of hCG with Different Doses and Schedules
Post by: SumTingWong on January 04, 2016, 02:36:12 pm
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I can write off the idea of daily dosing because it appears that one gets almost the same results with eod and probably even e3d dosing; the steady-state oscillations are not that large.

It's not my intention to make you anxious, I'm just trying to make the point that the study never claims to cover every dosage variable. Since 100IU doses (as an example) will cause less LH receptor downregulation, we simply don't know the outcome of these variables. The body does not always respond consistently to dosage changes in a linear fashion, especially in the long term. All I'm saying is, keep an open mind, and don't make assumptions.

My other point was that the study needs to be taken in context with the effect on estradiol. Don't blindly follow this study at the consequence to other effects of HCG, because there are many more than just raising testosterone.
Title: Re: Split: Pharmacokinetics of hCG with Different Doses and Schedules
Post by: Cataceous on January 04, 2016, 04:04:14 pm
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I can write off the idea of daily dosing because it appears that one gets almost the same results with eod and probably even e3d dosing; the steady-state oscillations are not that large.

It's not my intention to make you anxious, I'm just trying to make the point that the study never claims to cover every dosage variable. Since 100IU doses (as an example) will cause less LH receptor downregulation, we simply don't know the outcome of these variables. The body does not always respond consistently to dosage changes in a linear fashion, especially in the long term. All I'm saying is, keep an open mind, and don't make assumptions.

My other point was that the study needs to be taken in context with the effect on estradiol. Don't blindly follow this study at the consequence to other effects of HCG, because there are many more than just raising testosterone.

The study's authors claim to have selected a decent model of the hCG response process. It is not linear. If the model fails significantly at lower doses then it would be unlikely to generate a reasonable simulation of the impulse (single high dose) response; declining hCG plasma concentrations from the initial dose act in some respects as smaller doses later in time.

Your other point again neglects what I've said about estradiol and the study's potential usefulness in this regard.
Title: Re: Split: Pharmacokinetics of hCG with Different Doses and Schedules
Post by: SumTingWong on January 04, 2016, 04:44:19 pm
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Your other point again neglects what I've said about estradiol and the study's potential usefulness in this regard.

This debate has degraded into a pissing contest. I suggest we end it there before it gets any more silly.
Title: Re: Re: Thinking of going HCG Mono.. Or TRT temporarily.. thoughts?
Post by: Kierkegaard on January 04, 2016, 05:15:44 pm
...
Also, what about the effect on estradiol?  I'm assuming hCG stimulates aromatase in the leydig cells, but how?  Is it simply a matter of conversion from T to E2 via aromatase, as with exogenous testosterone?...

Though done on rats, this study (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC411596/) should be applicable and answer some of your questions.

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... These results demonstrate that purified Leydig cells have a high capacity for aromatization and that hCG can acutely stimulate aromatization independently of stimulating testosterone synthesis in vitro.

Thanks a lot for this and your previous study and contributions.