HCG induced Leydig Cell desensitization

[rick055]

From: https://thinksteroids.com/community/threads/134282294

Dr. Scalley wrote:


"For example, there is absolutely no support for the following statement. I challenge anyone to find support.

"It is important that no more than 500IU of HCG be administered on any given day. There is only just so much stimulation possible, and exceeding that not only is wasteful, doing so has important negative consequences. Higher doses overly stimulate testicular aromatase, which inappropriately raises estrogen levels, and brings on the detrimental effects of same. It also causes Leydig cell desentization to LH, and we are therefore inducing primary hypogonadism while perhaps treating secondary hypogonadism. 250IU QD is an effective, and safe, dose. After all, we are merely replacing that which is lost to inhibition.""

+++++++++++++++++++++

What about this, which suggests HCG induced desensitization can occur:

Effect of an antiestrogen on the testicular response to acute and chronic administration of hcg in normal and hypogonadotropic hypogonadic men: Tamoxifen and testicular response to hcg.

Levalle OA, Suescun MO, Fiszlejder L, Aszpis S, Charreau E, Guitelman A, Calandra R.

Division Endocrinologia, Hospital Carlos Durand, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.

The effect of the antiestrogen Tamoxifen (Tx) on the acute and chronic hcg administration was evaluated in patients with hypogonadotropic hypogonadism (HH) and in normal men. An hcg test (5000 IU hcg) was performed before, after two months of hcg administration (2000 IU hcg three times weekly) and after two months of hcg + Tx (2000 IU hcg three times weekly plus 20 mg/day of Tamoxifen). Blood samples were obtained before and following 24 and 72 h of every test to determine T, E, 17OHP and sex hormone binding globulin .

T increased only in HH with both treatments (X +/- SEM: Basal: 97.9 +/- 19.7; hcg: 237.7 +/- 43.2; hcg +/- Tx: 204.7 +/- 10.7 ng/100 ml).

17OHP rose with hcg alone, but not with hcg + Tx in both groups.

E, sex hormone binding globulin and 17OHP/T ratio did not change after treatments.

hcg tests:

E increased 24 h following hcg administration in every test. The ratio 17OHP/T rose at 24 h in the first and second test but in the third test it did not change.

These results support the role of E ]in the acute hcg-induced Leydig cell desensitization. However, the association of Tx does not improve T serum levels, suggesting that E might not be the unique factor involved in the mechanisms for testicular desensitization.

++++++++++++++++++++++++++++


And this, which suggests a dose of 250 - 350 iu is appropriate:

Title: Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression
Author: Yan, Xiaohua; Herbst, Karen L.; Sutton, Paul R.; Bremner, William J.; Wright, William W.; Anawalt, Bradley D.; Amory, John K.; Brown, Terry R.; Jarow, Jonathan P.; Zirkin, Barry R.; Coviello, Andrea D.; Matsumoto, Alvin M.
Abstract: In previous studies of testicular biopsy tissue from healthy men, intratesticular testosterone (ITT) has been shown to be much higher than serum testosterone (T), suggesting that high ITT is needed relative to serum T for normal spermatogenesis in men. However, the quantitative relationship between ITT and spermatogenesis is not known. To begin to address this issue experimentally, we determined the dose-response relationship between human chorionic gonadotropin (hCG) and ITT to ascertain the minimum dose needed to maintain ITT in the normal range. Twenty-nine men with normal reproductive physiology were randomized to receive 200 mg T enanthate weekly in combination with either saline placebo or 125, 250, or 500 IU hCG every other day for 3 wk. ITT was assessed in testicular fluid obtained by percutaneous fine needle aspiration at baseline and at the end of treatment. Baseline serum T (14.1 nmol/liter) was 1.2% of ITT (1174 nmol/liter). LH and FSH were profoundly suppressed to 5% and 3% of baseline, respectively, and ITT was suppressed by 94% (1234 to 72 nmol/liter) in the T enanthate/placebo group. ITT increased linearly with increasing hCG dose (P < 0.001). Posttreatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group, and 26% greater than baseline in the 500 IU hCG group. These results demonstrate that relatively low dose hCG maintains ITT within the normal range in healthy men with gonadotropin suppression. Extensions of this study will allow determination of the ITT concentration threshold required to maintain spermatogenesis in man.
URI: Page not found
Date: 2005-05

https://digital.lib.washington.edu/dspace/handle/1773/4415

++++++++++++++++++++

I don't ask this to restart an old argument, but because I am on this protocol. Also, I can say that, after 2.5 - 3 years of being on this protocol, I was able to get my wife pregnant the first time trying, with no modification to the protocol.

Granted, I am a sample size of n=1 and in theory we could have just gotten really, really lucky. After all, it only takes one sperm to do the job.

Can you explain (or reference a link where you have explained) why you feel the dose is insufficient and why the dosing two days in a row is inappropriate?

Certainly, we can agree to disagree, I'm just wondering what you propose as a better alternative than concurrent HCG administration.

Thanks.

 

[zkt]

Very interesting.
First I totally agree with Dr. Scally because 1) my own expermentation on myself bears the conclusion out and 2) the medical textbooks so indicate. In the past month Ive explained a few times how this class of receptors function.
Second, I dont see how the first study concludes that HCG induced desensitization can occur. Please post the whole thing, entire abstract, link or whatever else concerning this study you have. Would like to read it.
Third, the next study uses a high dose of TE so a more normal dose of say 125mg TE/w MIGHT give different results. Probably not, but worth noting.
Also,
"Posttreatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group, and 26% greater than baseline in the 500 IU hCG group. These results demonstrate that relatively low dose hCG maintains ITT within the normal range in healthy men with gonadotropin suppression. Extensions of this study will allow determination of the ITT concentration threshold required to maintain spermatogenesis in man."
Isnt this what one would expect? 500 iu produced more ITT than 250 or 125. One might be tempted to suspect that 1000iu would produce more ITT than 500 and so on.
This study indicates that the conventional treatment of hypogonadism, ie., T and low dose hcg works. It doesnt say a thing about high dose hcg.
Note also that the hcg dosing is eod and not on day 5 and/or 6 of the cycle when the serum levels of the T injection are at the lowest. Note also the half life of hcg is a little more than a day. So the 250 iu on day 6 is pretty well spent by mid week. Larger doses maintain serum levels longer.
Not exactly sure what your question is but hope this helps.

From: https://thinksteroids.com/community/threads/134282294

Dr. Scalley wrote:


"For example, there is absolutely no support for the following statement. I challenge anyone to find support.

"It is important that no more than 500IU of HCG be administered on any given day. There is only just so much stimulation possible, and exceeding that not only is wasteful, doing so has important negative consequences. Higher doses overly stimulate testicular aromatase, which inappropriately raises estrogen levels, and brings on the detrimental effects of same. It also causes Leydig cell desentization to LH, and we are therefore inducing primary hypogonadism while perhaps treating secondary hypogonadism. 250IU QD is an effective, and safe, dose. After all, we are merely replacing that which is lost to inhibition.""

+++++++++++++++++++++

What about this, which suggests HCG induced desensitization can occur:

Effect of an antiestrogen on the testicular response to acute and chronic administration of hcg in normal and hypogonadotropic hypogonadic men: Tamoxifen and testicular response to hcg.

Levalle OA, Suescun MO, Fiszlejder L, Aszpis S, Charreau E, Guitelman A, Calandra R.

Division Endocrinologia, Hospital Carlos Durand, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.

The effect of the antiestrogen Tamoxifen (Tx) on the acute and chronic hcg administration was evaluated in patients with hypogonadotropic hypogonadism (HH) and in normal men. An hcg test (5000 IU hcg) was performed before, after two months of hcg administration (2000 IU hcg three times weekly) and after two months of hcg + Tx (2000 IU hcg three times weekly plus 20 mg/day of Tamoxifen). Blood samples were obtained before and following 24 and 72 h of every test to determine T, E, 17OHP and sex hormone binding globulin .

T increased only in HH with both treatments (X +/- SEM: Basal: 97.9 +/- 19.7; hcg: 237.7 +/- 43.2; hcg +/- Tx: 204.7 +/- 10.7 ng/100 ml).

17OHP rose with hcg alone, but not with hcg + Tx in both groups.

E, sex hormone binding globulin and 17OHP/T ratio did not change after treatments.

hcg tests:

E increased 24 h following hcg administration in every test. The ratio 17OHP/T rose at 24 h in the first and second test but in the third test it did not change.

These results support the role of E ]in the acute hcg-induced Leydig cell desensitization. However, the association of Tx does not improve T serum levels, suggesting that E might not be the unique factor involved in the mechanisms for testicular desensitization.

++++++++++++++++++++++++++++


And this, which suggests a dose of 250 - 350 iu is appropriate:

Title: Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression
Author: Yan, Xiaohua; Herbst, Karen L.; Sutton, Paul R.; Bremner, William J.; Wright, William W.; Anawalt, Bradley D.; Amory, John K.; Brown, Terry R.; Jarow, Jonathan P.; Zirkin, Barry R.; Coviello, Andrea D.; Matsumoto, Alvin M.
Abstract: In previous studies of testicular biopsy tissue from healthy men, intratesticular testosterone (ITT) has been shown to be much higher than serum testosterone (T), suggesting that high ITT is needed relative to serum T for normal spermatogenesis in men. However, the quantitative relationship between ITT and spermatogenesis is not known. To begin to address this issue experimentally, we determined the dose-response relationship between human chorionic gonadotropin (hCG) and ITT to ascertain the minimum dose needed to maintain ITT in the normal range. Twenty-nine men with normal reproductive physiology were randomized to receive 200 mg T enanthate weekly in combination with either saline placebo or 125, 250, or 500 IU hCG every other day for 3 wk. ITT was assessed in testicular fluid obtained by percutaneous fine needle aspiration at baseline and at the end of treatment. Baseline serum T (14.1 nmol/liter) was 1.2% of ITT (1174 nmol/liter). LH and FSH were profoundly suppressed to 5% and 3% of baseline, respectively, and ITT was suppressed by 94% (1234 to 72 nmol/liter) in the T enanthate/placebo group. ITT increased linearly with increasing hCG dose (P < 0.001). Posttreatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group, and 26% greater than baseline in the 500 IU hCG group. These results demonstrate that relatively low dose hCG maintains ITT within the normal range in healthy men with gonadotropin suppression. Extensions of this study will allow determination of the ITT concentration threshold required to maintain spermatogenesis in man.
URI: Page not found
Date: 2005-05

https://digital.lib.washington.edu/dspace/handle/1773/4415

++++++++++++++++++++

I don't ask this to restart an old argument, but because I am on this protocol. Also, I can say that, after 2.5 - 3 years of being on this protocol, I was able to get my wife pregnant the first time trying, with no modification to the protocol.

Granted, I am a sample size of n=1 and in theory we could have just gotten really, really lucky. After all, it only takes one sperm to do the job.

Can you explain (or reference a link where you have explained) why you feel the dose is insufficient and why the dosing two days in a row is inappropriate?

Certainly, we can agree to disagree, I'm just wondering what you propose as a better alternative than concurrent HCG administration.

Thanks.

 

[terresw]

Are you saying that HCG leydig cell desensitization cannot occur?

I don't think Dr. Scally holds that position, if he does I would be interested to hear that from him.

Very interesting.
First I totally agree with Dr. Scally because 1) my own expermentation on myself bears the conclusion out and 2) the medical textbooks so indicate. In the past month Ive explained a few times how this class of receptors function.
Second, I dont see how the first study concludes that HCG induced desensitization can occur. Please post the whole thing, entire abstract, link or whatever else concerning this study you have. Would like to read it.
Third, the next study uses a high dose of TE so a more normal dose of say 125mg TE/w MIGHT give different results. Probably not, but worth noting.
Also,
"Posttreatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group, and 26% greater than baseline in the 500 IU hCG group. These results demonstrate that relatively low dose hCG maintains ITT within the normal range in healthy men with gonadotropin suppression. Extensions of this study will allow determination of the ITT concentration threshold required to maintain spermatogenesis in man."
Isnt this what one would expect? 500 iu produced more ITT than 250 or 125. One might be tempted to suspect that 1000iu would produce more ITT than 500 and so on.
This study indicates that the conventional treatment of hypogonadism, ie., T and low dose hcg works. It doesnt say a thing about high dose hcg.
Note also that the hcg dosing is eod and not on day 5 and/or 6 of the cycle when the serum levels of the T injection are at the lowest. Note also the half life of hcg is a little more than a day. So the 250 iu on day 6 is pretty well spent by mid week. Larger doses maintain serum levels longer.
Not exactly sure what your question is but hope this helps.

 

[zkt]

I think its more af a receptor down regulation issue and yes it happens. Actually the receptor activity is changing all the time as part of the homeostasis mechanism.

 

[rick055]

Again, I am assuming Dr. Scalley holds the following position(s). I say assuming, because I could have taken him out of context or missed something elsewhere:

1. HCG induced Leydig Cell desensitization does not occur. I believe he holds that position because he seemed to impugn the paragraph excerpted from Dr. Crisler's protocol in its entirety.

"It is important that no more than 500IU of HCG be administered on any given day. There is only just so much stimulation possible, and exceeding that not only is wasteful, doing so has important negative consequences. Higher doses overly stimulate testicular aromatase, which inappropriately raises estrogen levels, and brings on the detrimental effects of same. It also causes Leydig cell desentization to LH, and we are therefore inducing primary hypogonadism while perhaps treating secondary hypogonadism. 250IU QD is an effective, and safe, dose. After all, we are merely replacing that which is lost to inhibition.

The paragraph above which he criticizes is clear in stating doses above 500 iu not be administered on any given day given the propensity for high levels of testicular aromatase and subsequent Leydig Cell desensitization.

I infer from that Dr. Scalley does not believe in HCG induced Leydig Cell desensitization.

The cite for the study I posted is:

J Clin Endocrinol Metab 1980 Nov;51(5):1026-9


2. Dr. Scalley believes HCG taken at such a low dose (250 iu) is worthless. He is pretty clear as earlier in the thread he says:

"In my opinion, the hCG administration two days in a row is nonsense. Also, the dose is homeopathic (worthless). Care to provide support for this dosing?"


I think the second study I provided supports 250 iu as a reasonable dose to complement t induced hypogonadism.

I can't speak for him, but I believe Dr. Crisler has said he has never seen anyone need more than 350 iu. 250 - 350 iu would render somewhere from 7% less than baseline to over baseline, which is, I believe, the purpose of the HCG; to keep the testes functioning at 100%.

Some patients may need 250 iu for same, others may need up to 350 iu according to my understanding of his work.

But bottom line, I don't think it's fair to say 250 iu is a worthless dose. Again, I believe it maintained my fertility even after 2+ years on TRT. I also know that the difference in T levels on a week I take HCG compared to a week I don't is equivalent to what my beginning endogenous production was (i.e. 300 iu HCG gives me about 350 ng/dl, which is roughly my baseline T).


The only thing I cannot find support for is HCG administration the two days prior to the shot, specifically.

Again, I might have misinterpreted his position.

I know some docs favor T only cycled with periods of HCG only. I am wondering if that's what he feels is generally the way to go and why.

For the record, i don't think there's a "right and wrong"; two methods may have equal success in different areas. I'm just trying to understand.

But I do believe the statements he attacks can, in fact, be supported.

 

[zkt]

I cant speak for Dr. Scally but would be happy to discuss the issue of receptor mechanisms if I knew just what you want to know. Or is this a debate? If so clarify your position please.
I`m wading thru your posted info...
Ok I see the issue.

 

[zkt]

Consider the LH receptor:
G protein-coupled receptor - Wikipedia, the free encyclopedia

 

[zkt]

The cell increases the expression on the receptor (Up Regulates) in times of lessor stimulation ( low LH) and decreases expression on the receptor(DR) when LH is high. The receptor is a protein that the cell continually builds and which continually degrades. The cells that build the receptor proteins die(apotosis) and are reborn from stem cells.
Homeostasis is the key to understanding this."The body loves homeostasis" and strives to maintain a balance in all its processes and its intreactions with the enviroment.
LH is released thruout the day in pulses. So serum levels are constantly changing. The serum half-life of hcg is ~ 30 hrs. I dont remember the serum half-life of LH. Guess I could look it up or you could.
The piont is: you want to mimic the natural secretion of LH. Serum LH varies by a factor of, maybe 5, thruout the day. So a constant level is not good for the receptors. Causes DR.
Serum levels of an injection of hcg follow a predictable path (exponential decay) and are far from natural.
From my personal observations 250iu eod isnt worth the trouble. 1500 get me up depending upon baseline T. But I`m 62 yo, on 24 meds/d, and have a sexy wife.
This entire subject isnt well studied. What applies to one may not apply to another. If you really want to know you must study the texts, design and carry out experiments on yourself and objectively observe the results.
This is the scientific method.
Isnt this really what living is all about?

 

[rick055]

duplicate post

 

[rick055]

My issues are as follows:

1. It is my understanding that HCG can induce Leydig Cell desensitization. I believe it to be dose dependant.

2. If that's correct, I don't see the need to dose HCG higher than 500 iu. My thinking is this:

While there is naturally individual variability, it would appear that somewhere around 310 iu, on average, would promote 100% baseline levels. Since HCG can apparently desensitize the testes, why would one want to use more than what's individually required to maintain 100% baseline levels? Not only do you risk desensitization (perhaps not until much higher doses, but nonetheless...), but I believe that, after 500 iu, HCG disproportionately stimulates aromatase in many.

If the purpose of increasing HCG past that is only to increase T, why wouldn't you just use more exo-T? Shut down is shut down.

I dont know the rationale behind HCG on days 5 & 6, but I believe it is for hormonal variability.

+++++++++

My original thought was to ask Dr. Scalley why he doesn't believe HCG can desensitize the testes and what his preferred protocol is.

I don't know if it's periods of only T followed by periods of only HCG or concurrent use of T + HCG but at higher levels of HCG, different timing of HCG, etc...

All I can ascertain from his post is that he doesn't believe desensitization can occur and 250 - 350 iu HCG dosing is worthless and that there is no rationale for dosing on days 5 & 6.

Different docs do things differently - and that's fair, I'm trying to understand his rationale...

Further, (it appeared) he challenged us for something which suggested 250 ish iu HCG is not worthless and, IMO, if that's all it takes to maintain baseline function while on T, I think the paper I presented does that.

Same for the one on desensitization, but again, I can't tell definitively if he was even saying that didn't take place. Maybe I misunderstood.

 

[maxx1]

Im on HRT (hcg) and my doctor said that during his 25 years as adoctor he had NEVER heard of a single case of hcg desenticizing the testes and ive heard that from two other doctors here in Sweden and my dosage is 1500iu 3x week ,thats a normal hrt dose .

I know that Dr:swale says take only 500ius and so on but thats the opinion of one doctor,there are many many doctors that disagree..

 

[rick055]

Im on HRT (hcg) and my doctor said that during his 25 years as adoctor he had NEVER heard of a single case of hcg desenticizing the testes and ive heard that from two other doctors here in Sweden and my dosage is 1500iu 3x week ,thats a normal hrt dose .

I know that Dr:swale says take only 500ius and so on but thats the opinion of one doctor,there are many many doctors that disagree..

No doubt...

Are you HCG mono?

 

[Michael Scally MD]

I am appreciative of the qualifications of my posts by others so as to not take my writing out of context. But, it is clear from posts that many believe that hCG desensitization occurs at levels over 500 IU. Even though Crisler does qualify his statement as pointed out, the inference is that doses higher than what he advocates will cause desensitization. He is wrong. Further, I find his grasp and understanding of the literature to be wanting. And that is putting it kindly.

hCG desensitization does occur in cases of prolonged administration of 5,000 IU (Five Thousand). But, even here it is not a given and does not occur often and consistently. I am in total agreement with the immediate posts that this problem is almost never observed in clinical practice. Why the continued worry and hype about this problem is beyond me, but possibly Crisler helps feed this false idea.

I also agree with an earlier post in this threads that the two studies mention do nothing to support or demonstrate desensitization or the use of 250 IU X2 as useful therapy. If you really think about it, what is the purpose of the hCG two days in a row. This is totally and completely bizarre. As before, I challenge anyone to provide literature (article or citations) in support of his treatment(s). If Crisler is so sure of himself, why does he not cite support for the therapy or better publish the treatment. I have a simple answer - it is all in his head.

In the spirit of not repeating myself too much, I will repost some of the information from prior posts on this hCG question.

The study referenced, ?Coviello AD et al., (2005), Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression, J Clin Endocrinol Metab. 2005 May;90(5):2595-602,? will give some insight to the current hCG regimen that some of the forum members currently use with their TRT!!!

First, this is a study on intratesticular testosterone (ITT). The participants in this study were treated with T enanthate (TE), 200 mg im weekly, for rapid gonadotropin suppression in conjunction with a variable dose of hCG, delivered sc every other day for 3 wk: 0 (saline placebo), 125, 250, or 500 IU hCG. The placebo group served as the control group. [Note: Do you see a difference already! Even though the study does bot support Crisler, the dosing is much different.]

So, what we have are male subjects with elevated T levels due to exogenous T enanthate. Their endogenous production of T is completely suppressed (theoretically) as are their gonadotropins. ITT is suppressed due to the inhibition of gonadotropins from the exogenous T enanthate.

They found that each dose of hCG (125, 250, and 500 IU) returned the ITT concentration to normal. The data set being measured was not serum T, it was ITT. This should alert one to the stupidity of the research design. This was a waste of resources, in my opinion. The very simple reason is that in a normal male with a normal serum T their ITT will be ?normal.? All this study did was take a normal male and replace his T with exogenous T and than give hCG which replaced his LH. Duh ?

The one saving grace for the study is that it will be instructive to those using low dose hCG with their TRT. It does tell us something about hCG therapy while on TRT. I mentioned above that if one is going to use hCG while on TRT they should have something to observe, measure, and document. Why? If you are taking a drug, any drug, and do not have a dataset to monitor the effect of the drug you need to seriously think about what you are doing. I would ask them when did you decide to relinquish the control of your body?

It would be of interest to look at the data on serum T changes with each hCG dose . The subjects are on T enanthate so this is very similar to those on hCG with TRT. The finding is that the dose of hCG 125 IU every other day had NO effect on the serum T. The two higher doses did raise the serum T levels above normal. [Note: recall the dosing schedule!!!]

There is no individual data (always a cause for suspicion when reviewing literature) and there are no significance levels. Visual inspection of the graph, however, shows that the serum T level was not significantly different from control until day 21. If I was administering hCG less frequently than every other day and had no dataset to monitor I would be concerned.

Posters will do what they wish regardless of the literature. I respect that, particularly if someone feels they are getting a clinical response. I have treated over a 1000 patients for AIH and more for TRT. I did take the effort to research the treatments. And when I did develop a treatment for AIH, I published and presented the findings. I just happen to be skeptical of others who tout therapies based on their experience that has no basis in the literature. Further, they are treating patients as guinea pigs!

The following downloads are for the above article and another studying hCG administration, including "desensitization."

 

[rick055]

Thank you for the comprehensive reply, which triggers more questions in my mind.

Do you feel that higher doses of HCG begin to disproportionately stimulate aromatase and/or PROG?

In your opinion, what does a better protocol look like, generally? Do you think it's better to do T only followed by HCG only? Or do you just use higher doses of HCG concurrently and on different scheduling?

Is there a relationship between ITT and serum T?

Regardless, is it fair to say if ITT is @ 100% fertility would be expected to be maintained?

What are your thoughts on HCG monotherapy, generally?

 

[zkt]

My issues are as follows:

1. It is my understanding that HCG can induce Leydig Cell desensitization. I believe it to be dose dependant.
It is magnitude of the dose and the lenght of time the receptors are exposed to the dose. The receptors will down regulate with continued exposure to high levels of stimuation and conversely. At what point this happens is yet to be determined.

2. If that's correct, I don't see the need to dose HCG higher than 500 iu. My thinking is this:

While there is naturally individual variability, it would appear that somewhere around 310 iu, on average, would promote 100% baseline levels. Since HCG can apparently desensitize the testes, why would one want to use more than what's individually required to maintain 100% baseline levels? Not only do you risk desensitization (perhaps not until much higher doses, but nonetheless...), but I believe that, after 500 iu, HCG disproportionately stimulates aromatase in many.
how did you come up with 310 iu?

If the purpose of increasing HCG past that is only to increase T, why wouldn't you just use more exo-T? Shut down is shut down.
hcg stimulates the Leydig cells to pruduce T. Exogenous T doesnt.

I dont know the rationale behind HCG on days 5 & 6, but I believe it is for hormonal variability.
Because the serum T level from the injection in at the low point and to give variation in hcg levels.

+++++++++

My original thought was to ask Dr. Scalley why he doesn't believe HCG can desensitize the testes and what his preferred protocol is.

I don't know if it's periods of only T followed by periods of only HCG or concurrent use of T + HCG but at higher levels of HCG, different timing of HCG, etc...

All I can ascertain from his post is that he doesn't believe desensitization can occur and 250 - 350 iu HCG dosing is worthless and that there is no rationale for dosing on days 5 & 6.

Different docs do things differently - and that's fair, I'm trying to understand his rationale...

Further, (it appeared) he challenged us for something which suggested 250 ish iu HCG is not worthless and, IMO, if that's all it takes to maintain baseline function while on T, I think the paper I presented does that.

Same for the one on desensitization, but again, I can't tell definitively if he was even saying that didn't take place. Maybe I misunderstood.

...

 

[zkt]

How long have you been on this dose?

This is close to what I have expermimentially determined to equal a testosterone replacement dose and makes sense in terms of receptor regulation and mimicing the pituitary release of LH.
also 1500X3X4= ~20000iu/mth
But I find it difficult to believe that one can maintain the effects for years. I was stimulating my thyroid at this level.

How long have you been on this dose?

Im on HRT (hcg) and my doctor said that during his 25 years as adoctor he had NEVER heard of a single case of hcg desenticizing the testes and ive heard that from two other doctors here in Sweden and my dosage is 1500iu 3x week ,thats a normal hrt dose .

I know that Dr:swale says take only 500ius and so on but thats the opinion of one doctor,there are many many doctors that disagree..

 

[rick055]

...

1. I came up with 310 iu by interpolating the dose response curve between the 250 iu and 500 iu groups in the aforementioned.

2. I understand HCG stimulates endogenous production of testosterone. My question is, if 310 iu is, on average, enough to maintain 100% endogenous production (albeit in an eod dose), what is the rationale for exceeding this?

If the only purpose is to further increase testosterone, why not just raise the dose of exo-T?

My understanding is that by further increasing the dose of HCG you can begin to stimulate a lot of testicular aromatase. For now, we'll drop the theoretical possibility of desensitization.

3. I agree the rationale behind HCG on days 5 & 6 is hormonal variability - as well as picking up a weekly low spot due to the pks of T-CYP - I just couldn't find a study related to that point.

Ultimately, my main question would be why use more than (on average, individual patients differ) 250 - 350 iu HCG in conjunction with exogenous testosterone as part of TRT? I don't see the benefit, I only see additional risks. And I don't see the need to take that risk when increasing exo-T solves the problem of inadequate T levels.

That's what I'm trying to understand.

 

[zkt]

1. I came up with 310 iu by interpolating the dose response curve between the 250 iu and 500 iu groups in the aforementioned.
I dont that is valid. You would need to find the area under the curve of serum LH concentration vs. time for 24hrs to find the average serum LH level and then compare LH vs hcg receptor activity to determine a replacement dose of hcg.

2. I understand HCG stimulates endogenous production of testosterone. My question is, if 310 iu is, on average, enough to maintain 100% endogenous production (albeit in an eod dose), what is the rationale for exceeding this?
Because serum LH varies all over the place. It is released in spurts thru out the day. Constant levels of stimu;ation tend to cause receptor down-regulation.
If the only purpose is to further increase testosterone, why not just raise the dose of exo-T?
Why would you want to cause testicular atrophy if unnecessary?

My understanding is that by further increasing the dose of HCG you can begin to stimulate a lot of testicular aromatase. For now, we'll drop the theoretical possibility of desensitization.
I havent seen any proof of this

3. I agree the rationale behind HCG on days 5 & 6 is hormonal variability - as well as picking up a weekly low spot due to the pks of T-CYP - I just couldn't find a study related to that point.

Ultimately, my main question would be why use more than (on average, individual patients differ) 250 - 350 iu HCG in conjunction with exogenous testosterone as part of TRT? I don't see the benefit, I only see additional risks. And I don't see the need to take that risk when increasing exo-T solves the problem of inadequate T levels.
never said to take more than necessary to maintain testes. But large doses apparently dont so any harm. I`ve taken 20000iu/m for 3 mths or so and it didnt lose effectiveness. I think it would eventually at this dose. Our friend in Sweden hasnt said how long he has ben doing 1500/eod.

That's what I'm trying to understand.

...

 

[Michael Scally MD]

There are many errors in the above analysis. It is far too lengthy to put them in a post. One will demonstrate: a hCG dose of 300 IU will not normalize T serum T. If you are taking this from the ITT article, you are misinterpreting the article.

If i understand the post, the rational for the hCG two days in a row on Friday and Saturday before the Sunday injection is to assist in the lowest part of the week. If you read the literature on hCG effects, they come about 48-72 hours after injection. This schedule dosing is nonsense. I have a better question: produce literature that supports the use in this manner! Instead, we have theoretical and hypothetical baloney. And even that is based on imagined science.

For all practical purposes, hCG Leydig Cell desensitization does not exist within the clinical framework .

Why can I say this with absolute confidence? Because I have treated with success males with AIH, TRT, & hypogonadism. As above, this supposed problem is not seen in clinical care. Why do people continue to debate this point? This is a rumor that refuses to die. I wish to thank you for bringing this topic up since many who have been told this falsity will learn from the thread. Thanks.

 

[legalmandickslap]

For all practical purposes, hCG Leydig Cell desensitization does not exist within the clinical framework .

AMEN!