T Nation

Letro and HCG

[quote]oliiol wrote:
Drugs like Anastrozole work by blocking the production of estrogens in the body by binding to the enzyme aromatase.
[/quote]

That is incorrect.

Anastrozole is a competitive drug, that interferes with T reacting with the aromatase enzymes. It does not blind to aromatase. It competes with testosterone for access to aromatase. That is why one needs to take more adex when using more T.

There are some AIs that do bind to aromatase. More than one type.

[quote]KSman wrote:
oliiol wrote:
Drugs like Anastrozole work by blocking the production of estrogens in the body by binding to the enzyme aromatase.

That is incorrect.

Anastrozole is a competitive drug, that interferes with T reacting with the aromatase enzymes. It does not blind to aromatase. It competes with testosterone for access to aromatase. That is why one needs to take more adex when using more T.

There are some AIs that do bind to aromatase. More than one type.[/quote]

Um, no, it was correct.

His meaning was not “irreversibly bind” or chemically react, which would be characteristic of a suicide inhibitor, which anastrozole is not. I think that is what you had in mind and may have been how you were reading the post. All he meant was bind, in the simple sense, not irreversibly bind.

The way that a competitive inhibitor reduces an enzyme’s metabolism of other substrates, e.g. aromatase’s metabolism of testosterone, is by binding to the active site. At those moments when the inhibitor is bound to the enzyme, the enzyme cannot then metabolize anything else.

Your point though that more T requires more inhibitor is correct. That is characteristic of competitive inhibitors: if there is more substrate then the substrate competes more effectively for the binding site, so more inhibitor is needed.

And that i believe, is the exact reason there is an “estrogen rebound” after discontinuation of the AI is it not?

B

Actually, I don’t follow. When the aromatase inhibitor clears – which is usually somewhat slow with half-lives of several days – aromatase is left right back where it would be had there never been an AI (and had estrogen been at the same controlled level) so how this would relate to a rebound I’m not getting.

Cycles done what I consider to be the right way don’t give an estrogen rebound or what the user thinks to be an estrogen rebound anyway.

There are of course wrong ways to do cycles and what you refer to is a common complaint. I don’t know the cause. Guesses are:

  1. Depressed testosterone typical of doing a cycle the wrong way results in any given level of estrogen being much more estrogenic.

  2. Some practice of the wrong cycle, such as using way too high doses of HCG, may have upregulated aromatase, that is to say, caused more of it to be produced.

  3. Perhaps some practice of the wrong cycle upregulated the estrogen receptor

  4. Perhaps the increase in bodyfat resulting from an excessive number of weeks of bulking and getting much fatter than should have occurred is now resulting in greater degree of aromatization.

Anyway, if the cycle is not overly long, towards the end uses compounds that clear quickly, HCG is not used at excessive dose, HCG is not used during the recovery, excessive fat is not put on, Deca or EQ aren’t used anywhere at all near the end of the cycle, and standard SERM PCT is followed so far as I know problems with estrogen rebound are unheard of. Back when I did a very large number of consults (didn’t count but definitely over a thousand total) not one lifter ever suffered it from a cycle that I wrote or modified for them. So it certainly is not inevitable.

[quote]Bill Roberts wrote:
Actually, I don’t follow. When the aromatase inhibitor clears – which is usually somewhat slow with half-lives of several days – aromatase is left right back where it would be had there never been an AI (and had estrogen been at the same controlled level) so how this would relate to a rebound I’m not getting.

Cycles done what I consider to be the right way don’t give an estrogen rebound or what the user thinks to be an estrogen rebound anyway.

There are of course wrong ways to do cycles and what you refer to is a common complaint. I don’t know the cause. Guesses are:

  1. Depressed testosterone typical of doing a cycle the wrong way results in any given level of estrogen being much more estrogenic.

  2. Some practice of the wrong cycle, such as using way too high doses of HCG, may have upregulated aromatase, that is to say, caused more of it to be produced.

  3. Perhaps some practice of the wrong cycle upregulated the estrogen receptor

  4. Perhaps the increase in bodyfat resulting from an excessive number of weeks of bulking and getting much fatter than should have occurred is now resulting in greater degree of aromatization.

Anyway, if the cycle is not overly long, towards the end uses compounds that clear quickly, HCG is not used at excessive dose, HCG is not used during the recovery, excessive fat is not put on, Deca or EQ aren’t used anywhere at all near the end of the cycle, and standard SERM PCT is followed so far as I know problems with estrogen rebound are unheard of. Back when I did a very large number of consults (didn’t count but definitely over a thousand total) not one lifter ever suffered it from a cycle that I wrote or modified for them. So it certainly is not inevitable.[/quote]

Good stuff - ok fair enough then, it was just a semi educated guess really, thinking that as the AI only binds temporarily, then once it is discontinued then the full and peak amount of aromatase would be now suddenly active - giving a surge in aromatase activity.

But, that is assuming that the AI stops work suddenly and immediately, which it absolutely does not… plus when the drug is usually discontinued it is amidst a whole range of other manipulations - lowering of aromatising AAS levels, introduction of SERM’s etc… so i can see why an actual rebound is unlikely in a well constructed cycle.

Is it the case then, that the rebound idea is more of a theoretical one based on the non-suicide inhibition - rather than a practical one that occurs during the cycles designed by bodybuilders etc…?

Brook

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Similar to what happens to the leydigs after full HPTA suppression?

Also what happens to muscle tissue insulin sensitivity after low carb (low insulin) periods too…

Seems fair enough to me. :S

[quote] Brook wrote:
Is it the case then, that the rebound idea is more of a theoretical one based on the non-suicide inhibition - rather than a practical one that occurs during the cycles designed by bodybuilders etc…?

Brook[/quote]

The idea of estrogen rebound was being tossed around as of at least 15 years ago, maybe longer. I don’t suppose it is based on theory, but as an attempt to explain undesired post-cycle side effects from badly-done cycles.

It is possible that there are multiple causes. E.g., perhaps in one cycle the problem is having used Deca for 12 weeks and then being surprised at being impotent for quite some time after that. A steroid author might guess, just out of nowhere, that the problem was from lasting increased estrogen, and the lack of actual data showing that would be unlikely to stop him, in most cases.

Another cycle might have another undesired side effect from a different cause also attributed to increased estrogen.

In still another, maybe estrogen actually is increased, but not as a necessary consequence of doing an effective androgen cycle.

The concept of estrogen rebound was a fairly entrenched one even before aromatase inhibitors became popular. SERMs don’t downregulate the ER, nor does their discontinuance upregulate the ER so far as I know, so that at least is not, I think, a mechanism for traditional claims of estrogen rebound.

Whether possibly there is such an effect now from using an AI and bringing estrogen to a good low-normal level and then discontinuing it and seeing it go to mid-normal, I don’t know.

If there is it seems odd that it would be a major or lasting effect. Particularly as AI’s clear slowly anyway.

Also, as to reasons why “way back when” estrogen rebound was a theory being put out there, another likely cause was that back then, HCG was typically started only in recovery and so far as I know there wasn’t a single “steroid author” that recommended less than 5000 IU injections.

(So far as I know I was the first to say no to the madness and instead recommend 500 IU injections as a maximum.)

Those 5000 IU injections really did cause estrogen problems. Authors may not have realized their incorrect HCG protocol, not the androgen use, was the cause. But it wasn’t a “rebound”, it – when this was being done – was a directly-caused side effect of that recovery protocol.