Homeostasis of Estrogen in context of changing T dose

[Billegitimate]

Quick hypothetical for TRT purposes: My understanding is that our body attempts to maintain an E2 level that is appropriate by balancing T->E2 via aromatization and E2 clearance via the liver.

So my question is this: Is there a large range over which E2 levels will actually be maintained at an optimal level? Above this range and clearance rates are insufficient to reduce the E2 and below this level the T->E2 conversion isn't sufficient to generate enough E2.

So to put it into numbers for discussion, though not actual reference values, perhaps for one individual TT below 300 results in low estrogen, optimal ranges occur with TT from 300 to 1000, and then E2 spirals out of control above that. This latter scenario is when we use an AI to lower total T->E2 to a level that allows liver clearance rates to keep E2 where our body wants it.

I've had E2 within range after months with TT around 1300 and no AI...but then did some liver compromising things and saw my E2 shoot up out of range. I never feel as good on an AI as I do without it, even with E2 slightly over top of range.

I'm beginning to strongly suspect that TRT should be restricted to TT levels that don't require the use of an AI. If we want higher T levels for performance, muscle building, etc., then we need to look at how we reduce T->E2 conversion (get and stay lean?) and how we enhance clearance rates, perhaps by looking at competing pathways.

To this last point, this quote from Coffee and hormones: Here's how coffee really affects your health. | Precision Nutrition is interesting.

For instance, the liver detoxifies caffeine using the CYP1A2 enzyme system, which is also responsible for initial metabolism of estrogen during Phase I clearance by the liver. This is one reason caffeine is likely metabolized more slowly in women taking oral contraceptives or postmenopausal hormone replacement therapy.<br>

While research showing the effects of chronic caffeine consumption on circulating levels of estrogen isn’t yet available, researchers have suggested that caffeine consumption may lower the risk of breast cancer by upregulating the CYP1A2 isoenzyme and thus improving estrogen metabolism.​

Not sure I agree with the second paragraph. It would seem that caffeine and estrogen clearance compete for the same enzyme system. I wonder if pursuing liver health and eliminating caffeine consumption could allow higher TT levels without E2 problems.

Anyway, just musings and figured I'd throw them up here to see if anyone else had thoughts on it. For the next 6 weeks I intend to slightly lower my weekly T dose and pursue optimal clearance rates via dietary changes and eliminating or reducing caffeine consumption. Then I'll get T and E2 tested and begin ramping slowly back up in weekly dose until I find the highest range I can maintain without E2 issues.

 

[Megatron28]

The body attempts to maintain homeostasis of TT and E2 levels when the HPTA feedback loop is open. When you are using exogenous testosterone the feedback loop is closed. Therefore all of this can be thrown out the window. It just doesn't apply anymore.

 

[Billegitimate]

I can see that this throws some out of the window. But E2 clearance is still a variable and a large determinant is clearance rates. Otherwise, there would be a linear relationship between total T and E2.

Furthermore, I think the variances in clearance rates would explain why some individuals need no AI even on a heavy cycle while others need an AI on a relatively small TRT dose.

Obviously just my conjecture, but shutting down T production while on Exogenous T doesn't mean the entire HPTA feedback is broken. In fact, it is the HPTA attempt to lower T that causes the signal to the testes to stop. And in the face of elevated E2 SHBG elevates to attempt to get rid of it, an example of a loop that is still working to bring balance to the hormones.

 

[PrinceDianabol]

I can see that this throws some out of the window. But E2 clearance is still a variable and a large determinant is clearance rates. Otherwise, there would be a linear relationship between total T and E2.

Furthermore, I think the variances in clearance rates would explain why some individuals need no AI even on a heavy cycle while others need an AI on a relatively small TRT dose.
This can easily be explained by bodyfat %, amount of aromatase per adipocyte, genetics etc.

Obviously just my conjecture, but shutting down T production while on Exogenous T doesn't mean the entire HPTA feedback is broken. In fact, it is the HPTA attempt to lower T that causes the signal to the testes to stop. And in the face of elevated E2 SHBG elevates to attempt to get rid of it, an example of a loop that is still working to bring balance to the hormones.

I could be wrong here as I'm not sure if elevating e2 will bring up SHGB, but I'm fairly confident most guys on TRT/cycle find a drop in SHBG.

 

[Megatron28]

The difference in E2 levels among most guys is likely explained by the quantity of Aromatase Enzymes in their body. To a lesser degree in their ability to metabolize it.

 

[Billegitimate]

Perhaps. Regardless I'll be working both fronts. Since I feel crappy from anastrazole and exemestane my goal is the highest T I can get that still has E2 stable and acceptable.

So get as lean as I think I can maintain, minimize any other loads on liver function, and EOD subq t-cyp shots for stable levels. I hope I can stay at 1300-1400 TT with E2 in check. I know that I can maintain 1000+ with no need for an AI.

I'll be checking in as I go along. Recently benched 350, squatted 400 and strict pressed 225 so I've hit all my strength goals. Now I'll be a metcon machine and hit single digit Bodyfat and probably eliminate caffeine.

I'll then start a thread with lab work as I slowly ramp up my T dose and see at what point E2 starts to cascade out of control. Wish me luck. . Not looking forward to labs every month for a while, but I've done it before. I Enjoy experimenting and quantifying.

 

[Megatron28]

Perhaps. Regardless I'll be working both fronts. Since I feel crappy from anastrazole and exemestane my goal is the highest T I can get that still has E2 stable and acceptable.

So get as lean as I think I can maintain, minimize any other loads on liver function, and EOD subq t-cyp shots for stable levels. I hope I can stay at 1300-1400 TT with E2 in check. I know that I can maintain 1000+ with no need for an AI.

I'll be checking in as I go along. Recently benched 350, squatted 400 and strict pressed 225 so I've hit all my strength goals. Now I'll be a metcon machine and hit single digit Bodyfat and probably eliminate caffeine.

I'll then start a thread with lab work as I slowly ramp up my T dose and see at what point E2 starts to cascade out of control. Wish me luck. . Not looking forward to labs every month for a while, but I've done it before. I Enjoy experimenting and quantifying.

Depends on your body fat %. A lot of guys need an AI when their TT is that high. But some don't.

You may find DIM and Zinc helpful to help your body "clear" the estradiol faster.