hCG instructions

[Dr JIM]

Please reference: J Clin Endocrinol Metabolism
1982 Jul; 55 (1) 76-80
The word tolerance from my perspective may mean higher doses are needed to achieve the desired effect (elevated testosterone) or a identical dosage may result in an attenuated response over time. There are two more articles which I will locate, somewhere in my filing morass should you still not be satisfied, which also demonstrate "testicular desensitation" does indeed occur at a constant HCG dosages. This becomes particularily germane because fixed quantities of HCG are often used "during and or after a cycle" by BB and lifter's alike.
Furthermore since even doses approximating 500 IU can COMPLETLY eliminate endogenous LH production the effects of HCG on testosterone, may in effect be nullified, which is my rationale for suggesting an even lower "in cycle" dosage.
Best regards
Jim

 

[Bill Roberts]

At first on seeing the date, and not having checked yet to see if the study was online, I thought it might well have used 5000 IU injections or at least 2500 IU, as such was the norm at the time. It would have been unlikely to have used injections of the size I recommend, since they were not generally used.

Fortunately it turns out that the text is available online, as now it's a long drive to the medical library and so otherwise it might have been a while before I could have read it.

Actually their dosage was 1500 IU three times per week. Much too much, but at least not 5000 IU at a time.

On "in cycle use," suppression of LH really isn't an issue, and I don't know of any drawbacks to use at the 700-2000 total IU/week level.

 

[Dr JIM]

FYI
Sworder I suspect the most likely reason tolerance does not develop to regular LH stimuli is because it's secretion is pulsatile leading to a diurinal concentration pattern. The variable release of LH prevents steady state levels from becoming reality, especially considering it's very very short half life of several minutes.

 

[Sworder]

Would you say that it makes sense that other hormones would act in this manner as well? Also, if hormones did NOT follow this behavior tolerance would develop?

If my questions are too ambiguous I will state a direct question in place of the latter 2. What needs to happen for tolerance to build? In your opinion (I want to try to stimulate thought not force you take a stance

 

[Dr JIM]

Ah don't worry, I've always been willing to take a stance no matter how unconventional or controversial but in short I suspect continually saturated HCG binding foci may well decelerate, via down (or up) regulation of some unknown metabolic pathway, testosterone production. But I suspect your question is best deferred to B.R' for his thoughts and expertise in the field of biochemistry.

 

[Bill Roberts]

I don't think it's predictable, but rather something that is discovered by pharmacological research.

In terms of what goes on, there can be downregulation, desensitization, or both, or neither.

In some cases, cells change the number of receptors according to the amount of a hormone present. If this is reduced, that's downregulation.

It's also possible for cells to decrease their responsiveness to receptors being activated. This is desensitization.

Whether it occurs or not probably really is purely from whether over the course of time, animals did better with these in place or didn't.

Even if it might seem "a good idea" for downregulation or desensitization to be in place, it may not be. For example, it might be nice if adverse effect of androgens on blood lipid profile were downregulated. But there's no evidence that it's so.

Similarly, there might be no real need -- unless HCG secreting tumors used to be a real problem, enough to cause populations to adapt -- for desensitization to HCG (and probably LH) to occur, but when the doses are much higher than they need to be, it can occur.

EDIT: Maybe a problem driving selection in this direction could be variable HCG production in pregnancy. Desensitization to abnormally high HCG levels would protect the organism from overstimulation where HCG production is unusually high. Such a mechanism being in place for the ovaries could well result in the testes having it too. Just as utter guesswork.

If it is possible to predict what biology "should" do in each case, I don't know how!

So instead it is studied what nature does do.

 

[Bill Roberts]

It turns out on careful examination of the full text that while the abstract concludes that "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," their data actually not only doesn't support this conclusion, it supports the opposite conclusion.

This kind of thing does happen from time to time. (Conclusions in abstracts not actually being backed up by the data.)

In terms of response to the administered HCG during the therapy, T levels at the end of the therapy if anything were at their highest point, rather than having reduced with time. So that certainly doesn't support reduced sensitivity.

Where did they get their statement from then? Well, a 2000 IU injection of HCG didn't increase T levels anything beyond what the 1500 IU injections were doing.

That isn't surprising, and doesn't support the idea of reduced sensitivity compared to baseline or to any point during the treatment. It supports only that 1500 IU was eliciting maximal response or so near-maximal that any difference was undetectable given error margin and small number of subjects.