HCG induced desensitisation

[swifto]

HCG induced desensitisation? Does this occur?

Because I was off the opinoin it does not in sensible doses...

Int J Androl. 1985 Feb;8(1):28-36.

Effects of short- and long-term administration of tamoxifen on hCG-induced testicular steroidogenesis in man: no evidence for an oestradiol-induced steroidogenic lesion.
van Bergeijk L, Gooren LJ, van der Veen EA, de Vries CP.

hCG-induced testicular desensitization is characterized by inhibition at the level of the C-17,20-lyase enzyme. This defect has been attributed to an early rise in oestradiol (E2) following hCG administration. To test this hypothesis the E2-receptor antagonist, tamoxifen, was employed. From in vitro studies the evidence suggests that tamoxifen depletes the E2-receptor within 24 h. In this in vivo study, short-term (36 h) administration of tamoxifen (to 6 eugonadal men) did not affect basal plasma levels of LH, FSH, 17 alpha-hydroxyprogesterone (17-OHP), testosterone (T) and E2, whereas long-term (3 months) tamoxifen with treatment of 6 normogonadotrophic oligozoospermic men increased LH and T levels, indicating a biological effect of tamoxifen. The response of 17-OHP, T, E2 and the 17-OHP/T ratio to hCG was similar in short-term and long-term tamoxifen-treated men as well as in 6 untreated eugonadal male controls. These results do not suggest a role for endogenous E2 in the hCG-induced testicular steroidogenic block.

PMID: 3997269 [PubMed - indexed for MEDLINE]



Is there also a risk raising estrogen (E2) and progesteorone on cycle too much when using low dose HCG administartion when using exogenous testosterone, to prevent testicular dysfunction?

 

[BBC3]

Could you please translate that a little further. I am not sure if I am getting the jist of the article with what is there to read??

HCG induced desensitisation? Does this occur?

Because I was off the opinoin it does not in sensible doses...

Int J Androl. 1985 Feb;8(1):28-36.

Effects of short- and long-term administration of tamoxifen on hCG-induced testicular steroidogenesis in man: no evidence for an oestradiol-induced steroidogenic lesion.
van Bergeijk L, Gooren LJ, van der Veen EA, de Vries CP.

hCG-induced testicular desensitization is characterized by inhibition at the level of the C-17,20-lyase enzyme. This defect has been attributed to an early rise in oestradiol (E2) following hCG administration. To test this hypothesis the E2-receptor antagonist, tamoxifen, was employed. From in vitro studies the evidence suggests that tamoxifen depletes the E2-receptor within 24 h. In this in vivo study, short-term (36 h) administration of tamoxifen (to 6 eugonadal men) did not affect basal plasma levels of LH, FSH, 17 alpha-hydroxyprogesterone (17-OHP), testosterone (T) and E2, whereas long-term (3 months) tamoxifen with treatment of 6 normogonadotrophic oligozoospermic men increased LH and T levels, indicating a biological effect of tamoxifen. The response of 17-OHP, T, E2 and the 17-OHP/T ratio to hCG was similar in short-term and long-term tamoxifen-treated men as well as in 6 untreated eugonadal male controls. These results do not suggest a role for endogenous E2 in the hCG-induced testicular steroidogenic block.

PMID: 3997269 [PubMed - indexed for MEDLINE]



Is there also a risk raising estrogen (E2) and progesteorone on cycle too much when using low dose HCG administartion when using exogenous testosterone, to prevent testicular dysfunction?

 

[swifto]

I'm having this debate with a member at another board.

I stated HCG induced desensitisation doesnt occur in doses under 1000ius. He's stating it does occur when used for lengthy peroids (3 months), then cited that above study. Which I think has little importance.

 

[BBC3]

It has to occur. I am simly not getting the response I used to ..... And the situation seems to be getting worse.

I'm having this debate with a member at another board.

I stated HCG induced desensitisation doesnt occur in doses under 1000ius. He's stating it does occur when used for lengthy peroids (3 months), then cited that above study. Which I think has little importance.

 

[pmgamer18]

I know men this has happened to they did so much HCG there Testis became over worked and they ended up Primary there labs were low on T and high on LH and FSH all they needed to do was stop the HCG for a time and there testis come back. I know men on a lot of HCG don't have this problem it's about what your testis can handle. We all are not the same.

 

[swifto]

I know men this has happened to they did so much HCG there Testis became over worked and they ended up Primary there labs were low on T and high on LH and FSH all they needed to do was stop the HCG for a time and there testis come back. I know men on a lot of HCG don't have this problem it's about what your testis can handle. We all are not the same.

My argument was HCG should be used to prevent testicular dysfunction. The testis need to be stimulated and kept online. That was my opinoin.

The debate was that my protocol is ocunetrproductive due to desensitisation and a build up of estrogen and progesterone levels after prolonged use.

I'm still of the opinoin HCG should be used at 250-500ius 2x/wk but not for extreme preoids of time. Such as 3 months +

 

[Michael Scally MD]

It has to occur. I am simly not getting the response I used to ..... And the situation seems to be getting worse.

I am loathe to get into this argument, since hCG desensitization DOES NOT occur clinically. Despite this, I enjoy and like BBC3 posts, so, I ask, what is the response to which you refer?

 

[CubbieBlue]

I am loathe to get into this argument, since hCG desensitization DOES NOT occur clinically.

This.

 

[BBC3]

The blow up of the testicles. The response that I would always get from a good shot of HCG ranging anywhere from 1500 to 2500 ius at once. In my history, I would always wait 8-10 weeks and then begin a protocol spending (1) 5000iu ampule over about a 10 day period max. Usually in doses of 1000iu or higher. I have not been able to get the same reaction lately and I am just not sure why. I may have a batch damaged in the mail. Not sure. Since I first messed around with it I have used for maintenance while on HRT doses of T. Usually 500 iu every 3 or 4 days. I never really got the swelling or enlargement of the testes on this type dosing protocol. BUT that was this batch. I was able to get a good response from 5000ius about 7 months ago. Not lately though. I recently I have been through (4) 2500 iu injections over a 2 week period and no enlargement.!?!?!?!?

The response I am referring to seems to be an enlargement of the overall testicle, but primarily, I would consider myself to be having a major response by a swelling of the Epididynis throughout. And big time... Just not getting it anymore.

I am not doubting you in that there is no desensitization occuring. I guess I meant something is occuring and I am not sure what it is.... I am going on almost my second year of truely uninterrupted HRT and higher dosing, with 4 years total experience. Could it be that the LH and FSH suppression is starting to take a toll on the testicles that is becomming more difficult to recessitate? Thanks.

I am loathe to get into this argument, since hCG desensitization DOES NOT occur clinically. Despite this, I enjoy and like BBC3 posts, so, I ask, what is the response to which you refer?

 

[swifto]

Mike, could you please address my first post and the study.

Thanks.

 

[Michael Scally MD]

The blow up of the testicles. The response that I would always get from a good shot of HCG ranging anywhere from 1500 to 2500 ius at once. In my history, I would always wait 8-10 weeks and then begin a protocol spending (1) 5000iu ampule over about a 10 day period max. Usually in doses of 1000iu or higher. I have not been able to get the same reaction lately and I am just not sure why. I may have a batch damaged in the mail. Not sure. Since I first messed around with it I have used for maintenance while on HRT doses of T. Usually 500 iu every 3 or 4 days. I never really got the swelling or enlargement of the testes on this type dosing protocol. BUT that was this batch. I was able to get a good response from 5000ius about 7 months ago. Not lately though. I recently I have been through (4) 2500 iu injections over a 2 week period and no enlargement.!?!?!?!?

The response I am referring to seems to be an enlargement of the overall testicle, but primarily, I would consider myself to be having a major response by a swelling of the Epididynis throughout. And big time... Just not getting it anymore.

I am not doubting you in that there is no desensitization occuring. I guess I meant something is occuring and I am not sure what it is.... I am going on almost my second year of truely uninterrupted HRT and higher dosing, with 4 years total experience. Could it be that the LH and FSH suppression is starting to take a toll on the testicles that is becomming more difficult to recessitate? Thanks.

Thanks. This is what I thought and what you describe is probably a similar experience of others who claim hCG desensitization. The point being that the data is anecdotal reports of subjective measures. In my own experience, hCG administration for many causes a subjective feeling within the testicles. many even describe it as similar to "blue balls." The lack or absence of the subjective symptoms within the testicles over time does not translate into hCG desensitization.

In the area of hCG desensitization, there are no reports in the literature to support this effect clinically, both subjective and objective. That hCG desensitization occurs in the laboratory is unrefuted. It does not occur clinically.

 

[Michael Scally MD]

I know men this has happened to they did so much HCG there Testis became over worked and they ended up Primary there labs were low on T and high on LH and FSH all they needed to do was stop the HCG for a time and there testis come back. I know men on a lot of HCG don't have this problem it's about what your testis can handle. We all are not the same.

As I posted elsewhere, there is no report anywhere of hCG administration as a cause of primary hypogonadism. If you know of such a case, it would be the first in the entire known body of scientific literature. In other words, "put up or shut up." This is a continuing myth by those who purport to have knowledge while actually possessing none. This is along the line of the hCG diet, 24-hour urine testing for TRT, and FSH monitoring for TRT.

 

[Michael Scally MD]

HCG induced desensitisation? Does this occur?

Because I was off the opinoin it does not in sensible doses...

Is there also a risk raising estrogen (E2) and progesteorone on cycle too much when using low dose HCG administartion when using exogenous testosterone, to prevent testicular dysfunction?

hCG desensitization DOES NOT occur clinically. Anyone who says it does, does not know the literature, is trying to advance a myth, and probably believes in the hCG diet! Can hCG desensitization occur? Absolutely. There are many animal models demonstrating this effect, but, again, this effect is NOT seen clinically in FDA approved doses or less. Is there evidence for hCG desensitization in humans for hCG doses higher than FDA approved levels? Indirectly, a single study in does over 5,000 IU exploring testicular response to hCG administration reveals a leveling of T production.

hCG administration does stimulate estradiol and progesterone production. In fact, the estradiol rise occurs before the T rise.

The article "van Bergeijk L, Gooren LJ, van der Veen EA, de Vries CP. Effects of short- and long-term administration of tamoxifen on hCG-induced testicular steroidogenesis in man: no evidence for an oestradiol-induced steroidogenic lesion. Int J Androl 1985;8(1):28-36,: cited as support does nothing of the sort. This is a vain attempt to confuse the issue and by hopefully presenting a peer-reviewed article to win the argument. It ain't gonna work!

According to the abstract, the study examines the effect of tamoxifen hCG-induced testicular steroidogenesis. They do not use a model of hCG desensitization. The study is exploring a "local" effect of estradiol on T production. In fact, if you even give the slightest thought the study is about hCG desensitization, the study would not work!!! Duh . . . If the cells were desensitized to hCG, they would not produce estradiol or T, thus NO study on tamoxifen effects.


Another study (abstract below) cited by another forum is "Tang P-Z, Tsai-Morris CH, Dufau ML. Regulation of 3{beta}-Hydroxysteroid Dehydrogenase in Gonadotropin-Induced Steroidogenic Desensitization of Leydig Cells. Endocrinology 1998;139(11):4496-505." THIS IS A STUDY IN RATS!!! This expert is so desperate to prove him/herself. they cite rat studies. If we were to translate this study to humans, which is fraught with so many pitfalls, the easiest method is by dose (IU/kg). The dose for the rats is 100-125 IU/kg. For a 75 kg human, this would be 7,500 IU or more. A dose more than FDA approved, used clinically, and what they claim to cause hCG desensitization.


3{beta}-hydroxysteroid dehydrogenase/{Delta}5-{Delta}4 isomerases (3{beta}-HSD) are enzymes that catalyze the conversion of {Delta}5 to {Delta}4 steroids in the gonads and adrenal for the biosynthesis of sex steroid and corticoids. In gonadotropin-desensitized Leydig cells, from rats treated with high doses of human CG (hCG), testosterone production is markedly reduced, a finding that was attributed in part to reduction of CYP17 expression. In this study, we present evidence for an additional steroidogenic lesion induced by gonadotropin. Using differential display analysis of messenger RNA (mRNA) from Leydig cells of rats treated with a single desensitizing dose of hCG (2.5 {micro}g), we found that transcripts for type I and type II 3{beta}-HSD were substantially (5- to 8-fold) down-regulated. This major reduction, confirmed by RNase protection assay, was observed at the high hCG dose (2.5 {micro}g), whereas minor or no change was found at lower doses (0.01 and 0.1 {micro}g). In contrast, 3{beta}-HSD mRNA transcripts were not changed in luteinized ovaries of pseudopregnant rats treated with 2.5 {micro}g hCG. The down-regulation of 3{beta}-HSD mRNA in the Leydig cell resulted from changes at the transcriptional level. Western blot analysis showed 3{beta}-HSD protein was significantly reduced by hCG treatment, with changes that were coincidental with the reduction of enzyme activity and temporally consistent with the reduction of 3{beta}-HSD mRNA but independent of LH receptor down-regulation. The reduction of 3{beta}-HSD mRNA resulting from transcriptional inhibition of gene expression, and the consequent reduction of 3{beta}-HSD activity could contribute to the inhibition of androgen production in gonadotropin-induced steroidogenic desensitization of Leydig cells. The gender-specific regulation of 3{beta}-HSD by hCG reflects differential transcriptional regulation of the enzymes to accommodate physiological hormonal requirements and reproductive function.

 

[CubbieBlue]

As I posted elsewhere, there is no report anywhere of hCG administration as a cause of primary hypogonadism. If you know of such a case, it would be the first in the entire known body of scientific literature. In other words, "put up or shut up." This is a continuing myth by those who purport to have knowledge while actually possessing none. This is along the line of the hCG diet, 24-hour urine testing for TRT, and FSH monitoring for TRT.

Scally - not trying to put you on the spot, but I was looking through older threads and I found a post where you subscribed to desensitization. Here is a quote from you in that thread:

Partly right. Partly wrong. hCG 10000Iu will definitely produce desensitization quickly, possibly after the 1st injection but absolutely at three times/week. Desensitization has been shown to occur with 5000IU or higher and less frequently with lower amounts. This is assuming administration qod or greater. Also, the reason for the hCG is very important. Is it for spermatogenesis? T production? testicular size? androgenization?

Here is the thread:
https://thinksteroids.com/community/threads/134242214

What caused you to change your mind?

 

[Michael Scally MD]

Scally - not trying to put you on the spot, but I was looking through older threads and I found a post where you subscribed to desensitization. Here is a quote from you in that thread:

Partly right. Partly wrong. hCG 10000Iu will definitely produce desensitization quickly, possibly after the 1st injection but absolutely at three times/week. Desensitization has been shown to occur with 5000IU or higher and less frequently with lower amounts. This is assuming administration qod or greater. Also, the reason for the hCG is very important. Is it for spermatogenesis? T production? testicular size? androgenization?

Here is the thread:
https://thinksteroids.com/community/threads/134242214

What caused you to change your mind?

No problem - read the doses!!! I state 10,000 IU. The Desensitization has been shown to occur with 5000IU or higher and less frequently with lower amounts. is not inconsistent but a poor choice of wording. This is from the single study I cite about a leveling of T production, not an absence. These are all non-clinical doses. The key question does this effect occur clinically? I do not refute the ability to show this effect at very high doses. I have not changed my mind. Further, posters are claiming this effect with 1,000 IU. Thanks for reading and helping clarify the post.

 

[CubbieBlue]

No problem - read the doses!!! I state 10,000 IU. The Desensitization has been shown to occur with 5000IU or higher and less frequently with lower amounts. is not inconsistent but a poor choice of wording. This is from the single study I cite about a leveling of T production, not an absence. These are all non-clinical doses. The key question does this effect occur clinically? I do not refute the ability to show this effect at very high doses. I have not changed my mind. Further, posters are claiming this effect with 1,000 IU. Thanks for reading and helping clarify the post.

What are the guidelines for clinical usage? What the AACE suggests? Which I believe is 2,000 2x per week for monotherapy?

 

[Michael Scally MD]

What are the guidelines for clinical usage? What the AACE suggests? Which I believe is 2,000 2x per week for monotherapy?

I know of no clinical guidelines for hCG monotherapy in hypogonadism (i.e., TRT). I have attached the AACE and TES Guidelines. I do not advocate hCG as TRT alone. Who does?

 

[CubbieBlue]

I know of no clinical guidelines for hCG monotherapy in hypogonadism (i.e., TRT). I have attached the AACE and TES Guidelines. I do not advocate hCG as TRT alone. Who does?

You are right Scally, I had gone through that AACE manual before and believed it supported hCG for hypogonadal patients. Upon a second review it only advocates for its use in certain situations (IM no less...that seems pointless, no?)

Can you state your reasons for not supporting hCG monotherapy as a form of TRT?

 

[BBC3]

I am still confused about one thing. If it is given that testicular shutdown due to lack of signal can be marked by a decrease in size of the testicle, then what does it mean when one gets a lesser and lesser response to HCG therapy, when considering restoration of size? Dr. Scalley, do you think my case is simply a cumulative effect of the prolonged usage of exogenous T, and now due to prolonged exposure my testicles are becomming mre difficult to stimulate? And if so, should I begin a protocal that includes HMG as well.? I dont want to further "put my boys to sleep".....

 

[swifto]

hCG desensitization DOES NOT occur clinically. Anyone who says it does, does not know the literature, is trying to advance a myth, and probably believes in the hCG diet! Can hCG desensitization occur? Absolutely. There are many animal models demonstrating this effect, but, again, this effect is NOT seen clinically in FDA approved doses or less. Is there evidence for hCG desensitization in humans for hCG doses higher than FDA approved levels? Indirectly, a single study in does over 5,000 IU exploring testicular response to hCG administration reveals a leveling of T production.

hCG administration does stimulate estradiol and progesterone production. In fact, the estradiol rise occurs before the T rise.

The article "van Bergeijk L, Gooren LJ, van der Veen EA, de Vries CP. Effects of short- and long-term administration of tamoxifen on hCG-induced testicular steroidogenesis in man: no evidence for an oestradiol-induced steroidogenic lesion. Int J Androl 1985;8(1):28-36,: cited as support does nothing of the sort. This is a vain attempt to confuse the issue and by hopefully presenting a peer-reviewed article to win the argument. It ain't gonna work!

According to the abstract, the study examines the effect of tamoxifen hCG-induced testicular steroidogenesis. They do not use a model of hCG desensitization. The study is exploring a "local" effect of estradiol on T production. In fact, if you even give the slightest thought the study is about hCG desensitization, the study would not work!!! Duh . . . If the cells were desensitized to hCG, they would not produce estradiol or T, thus NO study on tamoxifen effects.


Another study (abstract below) cited by another forum is "Tang P-Z, Tsai-Morris CH, Dufau ML. Regulation of 3{beta}-Hydroxysteroid Dehydrogenase in Gonadotropin-Induced Steroidogenic Desensitization of Leydig Cells. Endocrinology 1998;139(11):4496-505." THIS IS A STUDY IN RATS!!! This expert is so desperate to prove him/herself. they cite rat studies. If we were to translate this study to humans, which is fraught with so many pitfalls, the easiest method is by dose (IU/kg). The dose for the rats is 100-125 IU/kg. For a 75 kg human, this would be 7,500 IU or more. A dose more than FDA approved, used clinically, and what they claim to cause hCG desensitization.


3{beta}-hydroxysteroid dehydrogenase/{Delta}5-{Delta}4 isomerases (3{beta}-HSD) are enzymes that catalyze the conversion of {Delta}5 to {Delta}4 steroids in the gonads and adrenal for the biosynthesis of sex steroid and corticoids. In gonadotropin-desensitized Leydig cells, from rats treated with high doses of human CG (hCG), testosterone production is markedly reduced, a finding that was attributed in part to reduction of CYP17 expression. In this study, we present evidence for an additional steroidogenic lesion induced by gonadotropin. Using differential display analysis of messenger RNA (mRNA) from Leydig cells of rats treated with a single desensitizing dose of hCG (2.5 {micro}g), we found that transcripts for type I and type II 3{beta}-HSD were substantially (5- to 8-fold) down-regulated. This major reduction, confirmed by RNase protection assay, was observed at the high hCG dose (2.5 {micro}g), whereas minor or no change was found at lower doses (0.01 and 0.1 {micro}g). In contrast, 3{beta}-HSD mRNA transcripts were not changed in luteinized ovaries of pseudopregnant rats treated with 2.5 {micro}g hCG. The down-regulation of 3{beta}-HSD mRNA in the Leydig cell resulted from changes at the transcriptional level. Western blot analysis showed 3{beta}-HSD protein was significantly reduced by hCG treatment, with changes that were coincidental with the reduction of enzyme activity and temporally consistent with the reduction of 3{beta}-HSD mRNA but independent of LH receptor down-regulation. The reduction of 3{beta}-HSD mRNA resulting from transcriptional inhibition of gene expression, and the consequent reduction of 3{beta}-HSD activity could contribute to the inhibition of androgen production in gonadotropin-induced steroidogenic desensitization of Leydig cells. The gender-specific regulation of 3{beta}-HSD by hCG reflects differential transcriptional regulation of the enzymes to accommodate physiological hormonal requirements and reproductive function.

Thanks.

Could you also please address this study which shows "...after 23 months of therapy, indicated that the testicular response was markedly reduced".



J Clin Endocrinol Metab. 1982 Jul;55(1):76-80.

Testicular responsiveness to chronic human chorionic gonadotropin administration in hypogonadotropic hypogonadism.
D'Agata R, Vicari E, Aliffi A, Maugeri G, Mongio A, Gulizia S.

Steroidogenic responsiveness to long term hCG administration (1500 U three times a week for 23 months) was characterized in 8 males with hypogonadotropic hypogonadism (HH). During hCG treatment, testosterone (T), which was in the prepuberal range under basal conditions, rose considerably to the upper end of the normal range and remained at that level during the 23 months of observation. A 2.5-fold increase was observed in serum levels of 17 beta-estradiol (E2) an increment less than seen with T. The increment in 17 alpha-hydroxyprogesterone was also lower than that in T throughout the study; thus, the 17 alpha-hydroxyprogesterone to T ratio, despite continuous hCG administration, remained low. Serum androstenedione was slightly increased during hCG therapy. No significant changes were observed in serum levels of dehydroepiandrosterone. These data indicate that continuous long term hCG administration stimulated T levels in HH, with a relatively small change in E2. The kinetics of the T and E2 responses to 2000 U hCG, evaluated after 23 months of therapy, indicated that the testicular response was markedly reduced. No increment in T levels was observed at 24 h; the maximal response occurred at 48 h. This pattern of T response supports the idea that partial testicular desensitization occurs in HH patients receiving chronic treatment with hCG