E rebound after AI cessation.

[Stretch]

I know where I stand on this. But where do you guys stand?

I am trying to accumulate as many research studies on the topic as possible.

Opinions are pretty much worthless imo. I have had a helluva time finding studies however.

 

[Stretch]

Aromasin no rebound
Armidex little rebound
Letro rebound

Clin Breast Cancer 2000 Sep;1 Suppl 1:S68-73

Comparison of in vitro exemestane activity versus other antiaromatase agents.

Soudon J.

Anastrozole, letrozole, and exemestane are the most selective and potent oral antiaromatase agents currently available. However, in vitro and in vivo studies comparing these agents are lacking. Anastrozole and letrozole are reversible, competitive nonsteroidal type II inhibitors, whereas exemestane is an irreversible steroidal type I inactivator. The study was conducted to determine the impact of this characteristic on in vitro residual aromatase activity and protein levels after incubation of JEG-3 cells with aminoglutethimide (a type II inhibitor), anastrozole, exemestane, or letrozole. Aromatase activity was measured after various incubation times with each antiaromatase agent at a concentration 10 times higher than IC50 (concentration giving 50% inhibition). Only exemestane induced a residual inhibition of aromatase activity after its removal, without any change in the aromatase protein level. Aromatase activity increased after preincubation of JEG-3 cells with either aminoglutethimide or anastrozole without any change in the aromatase protein level. The aromatase protein level increased rapidly when cells were incubated with letrozole and aromatase activity inhibition disappeared immediately after removal of the drug. The breakthrough effects in aromatase activity or protein levels observed after treatment with reversible inhibitors may be a factor in therapeutic failure with these agents. These results suggest a possible advantage for exemestane because it is the only clinically available oral irreversible aromatase inactivator.

Got this from an ADMIN at another board.

He heavily preaches that an E rebound DOES occur. Guess Dr. Scally is ignoring this, or maybe he just isn't aware of this study...

 

[Michael Scally MD]

This "estrogen rebound" is nothing more than some 'bro science term that is meaningless within the scientific literature. It infers what? After removal of an AI, estrogen levels will begin to return dependent on the AI PK/PD.

 

[Michael Scally MD]

Aromasin no rebound
Armidex little rebound
Letro rebound

Clin Breast Cancer 2000 Sep;1 Suppl 1:S68-73

Comparison of in vitro exemestane activity versus other antiaromatase agents.

Soudon J.

Anastrozole, letrozole, and exemestane are the most selective and potent oral antiaromatase agents currently available. However, in vitro and in vivo studies comparing these agents are lacking. Anastrozole and letrozole are reversible, competitive nonsteroidal type II inhibitors, whereas exemestane is an irreversible steroidal type I inactivator. The study was conducted to determine the impact of this characteristic on in vitro residual aromatase activity and protein levels after incubation of JEG-3 cells with aminoglutethimide (a type II inhibitor), anastrozole, exemestane, or letrozole. Aromatase activity was measured after various incubation times with each antiaromatase agent at a concentration 10 times higher than IC50 (concentration giving 50% inhibition). Only exemestane induced a residual inhibition of aromatase activity after its removal, without any change in the aromatase protein level. Aromatase activity increased after preincubation of JEG-3 cells with either aminoglutethimide or anastrozole without any change in the aromatase protein level. The aromatase protein level increased rapidly when cells were incubated with letrozole and aromatase activity inhibition disappeared immediately after removal of the drug. The breakthrough effects in aromatase activity or protein levels observed after treatment with reversible inhibitors may be a factor in therapeutic failure with these agents. These results suggest a possible advantage for exemestane because it is the only clinically available oral irreversible aromatase inactivator.

Got this from an ADMIN at another board.

He heavily preaches that an E rebound DOES occur. Guess Dr. Scally is ignoring this, or maybe he just isn't aware of this study...

This study is only pointing out the different AI PK/PD, nothing more. There is nothing in here about "estrogen rebound," whatever that is supposed to be. IF you ask any doctor/scientist to show you a study on "estrogen rebound," they will look at you funny.

Would you call the recovery in testosterone levels after stopping differing AAS, "testosterone rebound?" Or, the rise in DHT after stopping a 5ARi, "DHT rebound?"

 

[Stretch]

No. The inference is that E levels will spike ABOVE pre-treatment levels. I believe this to be ridiculous.

The study posted above shows that the theory is plausible, but would obviously require further testing in HUMANS, rather than cell cultures. Thanks to Dr. Jim, I know the theory was debunked by human trials.

But I am still seeking human clinical trials which show this "rebound" crap to be false.

 

[Michael Scally MD]

No. The inference is that E levels will spike ABOVE pre-treatment levels. I believe this to be ridiculous.

He study postes above shows that the theory is plausible, but would obviously require further testing in HUMANS, rather than cell cultures.

I am seeking human clinical trials which show this "rebound" crap to be false.

This does NOT happen. You will NOT find a study showing such a 'bro phenomenon. I will be happy to reverse course. So, I challenge anyone to find such a study. And, not some 'bro science connect-the-dots of mice, rats, ferrets, monkeys, ... where the 'bro makes 'bro logic.

It is up to them to show the proof. How are you able to prove a negative. It is not possible.

 

[Stretch]

Aromasin no rebound
Armidex little rebound
Letro rebound

Clin Breast Cancer 2000 Sep;1 Suppl 1:S68-73

Comparison of in vitro exemestane activity versus other antiaromatase agents.

Soudon J.

Anastrozole, letrozole, and exemestane are the most selective and potent oral antiaromatase agents currently available. However, in vitro and in vivo studies comparing these agents are lacking. Anastrozole and letrozole are reversible, competitive nonsteroidal type II inhibitors, whereas exemestane is an irreversible steroidal type I inactivator. The study was conducted to determine the impact of this characteristic on in vitro residual aromatase activity and protein levels after incubation of JEG-3 cells with aminoglutethimide (a type II inhibitor), anastrozole, exemestane, or letrozole. Aromatase activity was measured after various incubation times with each antiaromatase agent at a concentration 10 times higher than IC50 (concentration giving 50% inhibition). Only exemestane induced a residual inhibition of aromatase activity after its removal, without any change in the aromatase protein level. Aromatase activity increased after preincubation of JEG-3 cells with either aminoglutethimide or anastrozole without any change in the aromatase protein level. The aromatase protein level increased rapidly when cells were incubated with letrozole and aromatase activity inhibition disappeared immediately after removal of the drug. The breakthrough effects in aromatase activity or protein levels observed after treatment with reversible inhibitors may be a factor in therapeutic failure with these agents. These results suggest a possible advantage for exemestane because it is the only clinically available oral i
Got this from an ADMIN at another board.

He heavily preaches that an E rebound DOES occur. Guess Dr. Scally is ignoring this, or maybe he just isn't aware of this study...

i believe this is what he was referring to as suggesting the possibility for rebound.

 

[Michael Scally MD]

i believe this is what he was referring to as suggesting the possibility for rebound.

It would be best to have the full-text, but there is no inference of a "rebound." In fact, the cell culture system at 10 X IC50 measured aromatase activity in the presence of AI. In this case, the AI has a feedback on enzyme/activity levels. From the abstract, they attribute this to being a reversible inhibitor.

Again, this is a cell culture system designed to explore a specific aspect of AIs. In this instance, something that might be of interest to BrCa treatment. To extrapolate some 'bro science form something not even studies is typical BS.

 

[Michael Scally MD]

If I understand the 'bro science correctly, they are translating the reversible AI feedback on aromatase protein levels to be present after withdrawal of the AI, thus leading to more enzyme leading to more E2. This study did not look or find this to be the case. What this study was trying to explain is why reversible AIs have breakthrough in BrCa treatment.

The point of the study from the abstract is due to this positive feedback it is hard to suppress E2 levels. They did not test E2. At least not from the abstract. For the irreversible AI, there appears to be NO positive feedback on enzyme levels, thus maintaining lower E2 levels. Noteworthy is that the abstract provides no timeline. Wouldn't it be of import to know the enzyme decay? Could it be minutes or hours?

I suppose his argument is these increased enzyme levels are present after stopping an AI despite this being a cell culture system with 10 X IC50! Can one imagine these scenarios. 'Bro science does it all the time. That does not make it so. Ask him for a rat study. That is usually what they come up with. [Note: If rats were perfect mini-humans, why bother with clinical trials?]

 

[Stretch]

It is up to them to show the proof. How are you able to prove a negative. It is not possible.

Right, I know I won't be able to find a study that deals directly with E rebound after an AI. I was hoping to find clinical trials which contained the necessary data to indirectly prove my point. Blood tests both during and after AI use.

 

[Michael Scally MD]

Right, I know I won't be able to find a study that deals directly with E rebound after an AI. I was hoping to find clinical trials which contained the necessary data to indirectly prove my point. Blood tests both during and after AI use.

There are NO studies in AAS users using AIs. One would have to look at FEMALES with Breast Cancer. How relevant is that? I would say little to none, but if I see one I will report back.

 

[Dr JIM]

Agreed wholeheartedly DOC.

Dr S, I'm quite sure I uncovered a study in which pre and post E-2 levels were tested in those using AIs for gynecomastia AND estrogens simply returned to baseline upon cessation.


As I mentioned earlier Stretch, most "bros" have no idea what "rebound" means from a physiologic perspective anyway.

Has something more to do with what a ball does when it bounces off a wall I think!

 

[Stretch]

Thanks very much Docs.

Especially you Jim, our private correspondence, and your willingness to assist me has proved invaluable.

 

[CensoredBoardsSuck]

Thanks very much Docs.

Especially you Jim, our private correspondence, and your willingness to assist me has proved invaluable.

I had to double check to see if I was on Meso or another forum. It's turning into a veritable lovefest around here. Must be Meso in an alternate universe.

 

[Dr JIM]

Yea turns out Stretches fifth cousin of his fathers, mothers, uncle side, married my 6th cousin of my mothers, fathers, uncles 3rd niece!

I mean really how could two BB mates be so close yet so far, lol.

Of course it's Stretches fault, lol!

 

[CensoredBoardsSuck]

Yea turns out Stretches fifth cousin of his fathers, mothers, uncle side, married my 6th cousin of my mothers, fathers, uncles 3rd niece!

Sounds like you and Stretch come from the Appalachian Mountains.

Speaking of which, do you know what the trouble is with father's day in Appalachia?

It's the most confusing day of the year. [)] I'm kidding, I'm kidding.

 

[Dr JIM]

This is an excellent article in which refutes this garbola "rebound" phenomenon.

Although the studies primary outcome measure was the effect AI's have on Bone Mineral Density, pre and post AI therapy, estrogen levels were deemed necessary BECAUSE of the influence estrogen has on bone density.

Look at table FOUR for the summary.

Nonetheless, I do suspect some promoting the existing bro doctrine of "AI rebound" will remain partial and unmoved, since acknowledging the "truth" would contradict existing BB lore!

JIM

 

[Dr JIM]

Well I'm heartbroken, Stretch my 6th cousin on my mothers grandfathers nieces uncles side of the family, was just banned for generating unnecessary and inappropriate controversy for posting comments which conflict with conventional wisdom and existing literature on the topic of AI "rebound"'.

It seems my mate has been eschewed and ostracized for "telling the truth".

But "bro science" LIVES on to contest the evil spirits of secular science and to fight another day, no doubt with a less worthy adversary than my 6th cousin on my mothers .......

 

[Stretch]

Yeah, they banned me, it was amazing to see the vehemence with which they defended their errant beliefs. They had no desire to know the truth.

 

[CensoredBoardsSuck]

Yeah, they banned me, it was amazing to see the vehemence with which they defended their errant beliefs. They had no desire to know the truth.

It's not surprising. Bro forums will only accept evidence if it affirms their beliefs but as you discovered, the evidence they do accept is usually misinterpreted. You giving them the truth was an act of heresy that could shatter their little fantasy world, so you had to go. You're better off anyway. Those forums offer nothing of value and are a waste of time.