THE-DET-OAK
IncreasedMyT @ ULV
im stealing this from DR Scally it is his argument.
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.
next post
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 testosterone replacement therapy (TRT), and FSH monitoring for testosterone replacement therapy (TRT).
next
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
next
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.
so here he is saying as long as you dont go over 5000 iu
next
I was hoping to obtain the full-text document, but no luck. If anyone has it, either post of forward. This article from 1982 does not show hCG desensitization. In fact, the article states, ”These data indicate that continuous long term hCG administration stimulated T levels in HH.” The only note for “partial desensitization” is a delayed "kinetic" response to hCG administration from 24 to 48 hours! It is also of interest this was over 23 months, almost 2 years with a three times per week schedule. This is a long time, yet they state the above – there continued to be T production. It would be nice to know what the hCG concentration is at this schedule after almost 2 years. The following abstract that used an every 6 day schedule over a year found a consistent T production. Moreover they note that maximal T production occurs 58 hours after injection.
D'Agata R, Vicari E, Aliffi A, Maugeri G, Mongiol A, Gulizia S. Testicular Responsiveness to Chronic Human Chorionic Gonadotropin Administration in Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab 1982;55(1):76-80.
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.
Balducci R, Toscano V, Casilli D, Maroder M, Sciarra F, Boscherini B. Testicular responsiveness following chronic administration of hCG (1500 IU every six days) in untreated hypogonadotropic hypogonadism. Horm Metab Res 1987;19(5):216-21.
The observation that the testosterone (T) response to a single intramuscular injection of hCG is prolonged suggests that currently used regimens (2-3 injections per week) to stimulate endogenous androgen secretion in hypogonadotropic hypogonadism (HH) patients have to be reassessed. Moreover, during the last few years, Leydig cell steroidogenic desensitization has been found after massive doses of hCG. The aim of the present investigation, carried out in 6 HH patients who showed no signs of puberty, was to study the effect of 1500 IU hCG administered every six days over a period of one year to induce the onset of pubertal development. To evaluate the kinetics of the response of T, 17 alpha-hydroxyprogesterone (17 alpha-OHP) and 17 beta-oestradiol (E2), blood samples were taken basally and 1, 2, 4 and 6 days after drug injection. This dynamic study was performed after the first injection and after the 4th and 12th month of treatment. During this one year time period, a progressive increase in testicular size was observed. Comparing plasma T levels (mean +/- SE) before the first injection (11.2 +/- 4.7 ng/dl) with the corresponding values at the 4th (38.7 +/- 10.5 ng/dl) and 12th months (99.5 +/- 19.9 ng/dl) of therapy, a progressive and significant increase was observed. T reached a maximum elevation 58 hours after hCG injection at the 4th month (198.3 +/- 42 ng/dl; P less than 0.01) and at the 12th month (415.6 +/- 62.6 ng/dl; P less than 0.05), whereas it remained unchanged following the first hCG injection.(ABSTRACT TRUNCATED AT 250 WORDS)
next
Another thread brought to mind a study on hCG and body composition (and other factors). [ Hypogonadism / Wanna do Steroids - PLEASE HELP! ] In that study, hCG was given at 5,000 IU twice weekly. In a similar doing study following, the T level increased. The dose of 5,000 IU is above what I recommend and what I see in use. I hope the myth of hCG desensitization can be laid to rest, but I know many will continue to hold onto this fairy tale.
Liu, PY, SM Wishart, DS Celermajer, et al., Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo-controlled clinical trial of recombinant human chorionic gonadotropin. Eur J Endocrinol, 2003. 148(1): p. 55-66.
OBJECTIVE: In order to assess the hormonal determinants of insulin sensitivity and related components of the metabolic syndrome, we evaluated the effect of subcutaneous recombinant human chorionic gonadotropin (r-hCG; Ovidrel) on insulin sensitivity, vascular reactivity, leptin, insulin-like growth factor-I (IGF-I) and lipids in ambulant, community dwelling men >60 Years of age with serum testosterone <or= 15 nmol/l on two occasions. DESIGN: Forty eligible men were randomized to receive 250 microg (5000 IU) r-hCG subcutaneously twice each week (n=20) or placebo (n=20) injections for 3 Months, and all subjects (mean age 67 (range 60-85) Years) completed the study.
METHODS AND RESULTS: Groups were well matched for height, weight, anthropometry and insulin sensitivity. Insulin sensitivity was assessed by homeostasis model (HOMA) and euglycemic hyperinsulinemic clamp at baseline and at the end of the treatment period in the first 30 men who did not have diabetes mellitus. Insulin sensitivity (HOMA and euglycemic clamp) or beta cell function (HOMA) were not significantly changed by r-hCG despite a significant increase in lean body mass (approximately 2 kg, P<0.001) and reduced fat mass (approximately 1 kg, P<0.05). Subcutaneous fat (skinfold measurements), abdominal girth and serum leptin all decreased and IGF-I tended to increase, but these changes were not significant. Recombinant hCG significantly reduced total and low density lipoprotein cholesterol, and triglycerides, but did not significantly alter high density lipoprotein cholesterol. Endothelial function (vascular reactivity) was not significantly worsened. We conclude that three-Months of treatment with r-hCG demonstrates expected hormonal effects, improved lipids and did not worsen vascular endothelial function. Insulin sensitivity was not altered despite suggestive changes in body composition.
CONCLUSIONS: These findings suggest short-term metabolic and cardiovascular safety and argue against an important role for androgens in the hormonal control of insulin sensitivity in older men.
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.
next post
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 testosterone replacement therapy (TRT), and FSH monitoring for testosterone replacement therapy (TRT).
next
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
next
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.
so here he is saying as long as you dont go over 5000 iu
next
I was hoping to obtain the full-text document, but no luck. If anyone has it, either post of forward. This article from 1982 does not show hCG desensitization. In fact, the article states, ”These data indicate that continuous long term hCG administration stimulated T levels in HH.” The only note for “partial desensitization” is a delayed "kinetic" response to hCG administration from 24 to 48 hours! It is also of interest this was over 23 months, almost 2 years with a three times per week schedule. This is a long time, yet they state the above – there continued to be T production. It would be nice to know what the hCG concentration is at this schedule after almost 2 years. The following abstract that used an every 6 day schedule over a year found a consistent T production. Moreover they note that maximal T production occurs 58 hours after injection.
D'Agata R, Vicari E, Aliffi A, Maugeri G, Mongiol A, Gulizia S. Testicular Responsiveness to Chronic Human Chorionic Gonadotropin Administration in Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab 1982;55(1):76-80.
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.
Balducci R, Toscano V, Casilli D, Maroder M, Sciarra F, Boscherini B. Testicular responsiveness following chronic administration of hCG (1500 IU every six days) in untreated hypogonadotropic hypogonadism. Horm Metab Res 1987;19(5):216-21.
The observation that the testosterone (T) response to a single intramuscular injection of hCG is prolonged suggests that currently used regimens (2-3 injections per week) to stimulate endogenous androgen secretion in hypogonadotropic hypogonadism (HH) patients have to be reassessed. Moreover, during the last few years, Leydig cell steroidogenic desensitization has been found after massive doses of hCG. The aim of the present investigation, carried out in 6 HH patients who showed no signs of puberty, was to study the effect of 1500 IU hCG administered every six days over a period of one year to induce the onset of pubertal development. To evaluate the kinetics of the response of T, 17 alpha-hydroxyprogesterone (17 alpha-OHP) and 17 beta-oestradiol (E2), blood samples were taken basally and 1, 2, 4 and 6 days after drug injection. This dynamic study was performed after the first injection and after the 4th and 12th month of treatment. During this one year time period, a progressive increase in testicular size was observed. Comparing plasma T levels (mean +/- SE) before the first injection (11.2 +/- 4.7 ng/dl) with the corresponding values at the 4th (38.7 +/- 10.5 ng/dl) and 12th months (99.5 +/- 19.9 ng/dl) of therapy, a progressive and significant increase was observed. T reached a maximum elevation 58 hours after hCG injection at the 4th month (198.3 +/- 42 ng/dl; P less than 0.01) and at the 12th month (415.6 +/- 62.6 ng/dl; P less than 0.05), whereas it remained unchanged following the first hCG injection.(ABSTRACT TRUNCATED AT 250 WORDS)
next
Another thread brought to mind a study on hCG and body composition (and other factors). [ Hypogonadism / Wanna do Steroids - PLEASE HELP! ] In that study, hCG was given at 5,000 IU twice weekly. In a similar doing study following, the T level increased. The dose of 5,000 IU is above what I recommend and what I see in use. I hope the myth of hCG desensitization can be laid to rest, but I know many will continue to hold onto this fairy tale.
Liu, PY, SM Wishart, DS Celermajer, et al., Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo-controlled clinical trial of recombinant human chorionic gonadotropin. Eur J Endocrinol, 2003. 148(1): p. 55-66.
OBJECTIVE: In order to assess the hormonal determinants of insulin sensitivity and related components of the metabolic syndrome, we evaluated the effect of subcutaneous recombinant human chorionic gonadotropin (r-hCG; Ovidrel) on insulin sensitivity, vascular reactivity, leptin, insulin-like growth factor-I (IGF-I) and lipids in ambulant, community dwelling men >60 Years of age with serum testosterone <or= 15 nmol/l on two occasions. DESIGN: Forty eligible men were randomized to receive 250 microg (5000 IU) r-hCG subcutaneously twice each week (n=20) or placebo (n=20) injections for 3 Months, and all subjects (mean age 67 (range 60-85) Years) completed the study.
METHODS AND RESULTS: Groups were well matched for height, weight, anthropometry and insulin sensitivity. Insulin sensitivity was assessed by homeostasis model (HOMA) and euglycemic hyperinsulinemic clamp at baseline and at the end of the treatment period in the first 30 men who did not have diabetes mellitus. Insulin sensitivity (HOMA and euglycemic clamp) or beta cell function (HOMA) were not significantly changed by r-hCG despite a significant increase in lean body mass (approximately 2 kg, P<0.001) and reduced fat mass (approximately 1 kg, P<0.05). Subcutaneous fat (skinfold measurements), abdominal girth and serum leptin all decreased and IGF-I tended to increase, but these changes were not significant. Recombinant hCG significantly reduced total and low density lipoprotein cholesterol, and triglycerides, but did not significantly alter high density lipoprotein cholesterol. Endothelial function (vascular reactivity) was not significantly worsened. We conclude that three-Months of treatment with r-hCG demonstrates expected hormonal effects, improved lipids and did not worsen vascular endothelial function. Insulin sensitivity was not altered despite suggestive changes in body composition.
CONCLUSIONS: These findings suggest short-term metabolic and cardiovascular safety and argue against an important role for androgens in the hormonal control of insulin sensitivity in older men.
