HCG induced desensitisation

[Michael Scally MD]

Thanks.

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

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)

 

[Michael Scally MD]

Another thread brought to mind a study on hCG and body composition (and other factors). [ https://thinksteroids.com/community/posts/671918 ] 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.

 

[zkt]

If anything is gonna down-reguloate the LH receptor in the testis it a constant high serum level of hcg as per the textbooks. Keeping in mind the T1/2. Perhaps what you experience over the past 4 years is the result of age and not long term hcg use ? I have come to the conclusion that a large dose 1500-2000iu/ 7-10 days maximizes the effect you speak of , at least, for me. Maybe lay off the hcg for a few weeks and then give 2000iu sc, wait a couple days and repeat.
10000iu divided into 4-6 doses over 4-6 weeks works for me. Your mileage mat vary depending on the condition of your HPTA axis, of course.

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.