Does injectable E2 cause the same side effects as aromatised E2?

[bananafeet]

Probably a dumb question. My various ramblings with ChatGPT has led to to understand that certain tissues have more aromatse enzyme than others.

As a result aromatisation of testosterone can cause elevated paracrine (local) levels of estrodial in certain tissues verses the blood levels.

So that would lead to the question: would taking my E2 from 100pmol (27pg/mL) to 250pmol (68pg/mL) using estrodial cypionate cause the same side effects as if I had that level through aromatisation of testosterone?

Keep in mind I started getting painful nipples at 174pmol (47pg/mL) on testosterone enanthate (175mg per week).

Why? I want to see if I can lower my lipids using E2 rather than taking a statin to reduce my CVD risk. Obviously taking into account blood pressure and side effects.

Thanks!

 

[CorgisOnTren]

Yes, taking exogenous estrogen will cause it to do estrogenic things in your body.

 

[bananafeet]

Yes, taking exogenous estrogen will cause it to do estrogenic things in your body.

My question is slightly more nuanced than that. But I guess the only way to find out...

 

[Ghoul]

My question is slightly more nuanced than that. But I guess the only way to find out...

What are your lipid levels?

 

[bananafeet]

What are your lipid levels?

Sure early June after coming off a cycle for a few weeks (on 125mg test E, 200mg masteron):
Fasted:
Total Cholesterol: 4.6 mmol/L (below 4.0)
Triglycerides: 1.4 mmol/L (below 2.0)

CHOLESTEROL FRACTIONS
HDL: 1.02 mmol/L (above 1.0)
LDL (calculated): 2.94 mmol/L (below 2.5)
Non-HDL cholesterol: 3.58 mmol/L (below 3.3)
Total/HDL ratio: 4.5

End of the last cruise in March (125mg test E, 100mg nandralone):
Status: Random

Cholesterol: 4.6 mmol/L
Triglyceride: 1.1 mmol/L
HDL-C: 1.1 mmol/L
LDL-C: 3.0 mmol/L
TC/HDL-C ratio: 4.2
Non-HDL-C: 3.5 mmol/L

I'm expecting it to improve a bit more because I've started Tirzepatide and lowered my androgen load (62.5mg test E, 50mg nandralone) as I'm trying to drop my HCT down. It crept up to 0.51 I prefer it around 0.49, same for my haemoglobin which is top of the reference range (174 vs low 160s).

 

[Ghoul]

Your HDL is already very good, and the absolute most you could theoretically get from supraphysiological e2 is around a 15% drop in LDL.

You could easily lower it more than that with ezetimebe and bempedoic acid.

Though Pitavastatin likely avoids everything that concerns you about statins, if you can get it, and combined with eze provides a 65% drop in LDL and 10-15% boost in HDL.

 

[bananafeet]

Your HDL is already very good, and the absolute most you could theoretically get from supraphysiological e2 is around a 20 point drop in LDL.

You could easily lower it more than that with ezetimebe and bempedoic acid.

Though Pitavastatin likely avoids everything that concerns you about statins, if you can get it, and combined with eze provides a 65% drop in LDL and 10-15% boost in HDL.

Thanks I'll look into those for my next order. I plan on dropping other 20kg so that should help too as well as dietary adjustments and cardio as my fitness improves.

The data on higher E2 levels being associated with lower CVD piqued my interest. I think I will still do 4 weeks at 0.8mg Estrodial Cypionate and see what it does to my bloodwork.

Man medicine on YouTube gave me the idea as he noticed better Apob and lipids from exogenous E2 than an expensive medication was taking. His levels were like 93pg/mL with no side effects. IGF1 unaffected apparently as well.

 

[Ghoul]

Thanks I'll look into those for my next order. I plan on dropping other 20kg so that should help too as well as dietary adjustments and cardio as my fitness improves.

The data on higher E2 levels being associated with lower CVD piqued my interest. I think I will still do 4 weeks at 0.8mg Estrodial Cypionate and see what it does to my bloodwork.

Man medicine on YouTube gave me the idea as he noticed better Apob and lipids from exogenous E2 than an expensive medication was taking. His levels were like 93pg/mL with no side effects. IGF1 unaffected apparently as well.

I'm surprised IGF didn't increase.

Well, whatever you do, getting LDL down and keeping it low is guaranteed to reduce your risk of cardiovascular disease.

Don't forget BP too. Equally important to lower risk.

 

[HUGE McBIGLARGE]

There is a difference in effect between systemic serum estradiol (including exogenous estradiol) when compared to estradiol that has derived from peripheral aromatisation.

As you said, different tissues express different amounts of enzymes, which includes aromatase. Off the top of my head, the brain and skin have a disproportionately high amount of aromatase compared to the mean of your body. This means some tissues have more estrogenicity compared to others.

Women derive most of their estradiol from ovarian release, which means it is systemic. Men derive most of theirs from peripheral aromatisation (I think) which then finds its way into blood and becomes systemic.

Systemic estradiol is sufficient for estrogenicity without the need for significant peripheral aromatisation, as women do just fine without much peripheral aromatisation.

Can you get low e2 symptoms despite normal serum e2? Not likely, but possible due to niche circumstances such as estrogen insensitivity or estrogen antagonism from high androgenicity.

Can you get high e2 symptoms despite normal serum e2? Yes. You could get gyno from peripheral aromatisation if your breast tissue has a lot of aromatase. Or if your breast tissue is particularly sensitive to estrogen.

Ultimately, it probably makes very little real world difference to any symptoms or biomarkers whether your estradiol is derived from exogenous e2 or from T-to-e2 aromatisation

 

[bananafeet]

There is a difference in effect between systemic serum estradiol (including exogenous estradiol) when compared to estradiol that has derived from peripheral aromatisation.

As you said, different tissues express different amounts of enzymes, which includes aromatase. Off the top of my head, the brain and skin have a disproportionately high amount of aromatase compared to the mean of your body. This means some tissues have more estrogenicity compared to others.

Women derive most of their estradiol from ovarian release, which means it is systemic. Men derive most of theirs from peripheral aromatisation (I think) which then finds its way into blood and becomes systemic.

Systemic estradiol is sufficient for estrogenicity without the need for significant peripheral aromatisation, as women do just fine without much peripheral aromatisation.

Can you get low e2 symptoms despite normal serum e2? Not likely, but possible due to niche circumstances such as estrogen insensitivity or estrogen antagonism from high androgenicity.

Can you get high e2 symptoms despite normal serum e2? Yes. You could get gyno from peripheral aromatisation if your breast tissue has a lot of aromatase. Or if your breast tissue is particularly sensitive to estrogen.

Ultimately, it probably makes very little real world difference to any symptoms or biomarkers whether your estradiol is derived from exogenous e2 or from T-to-e2 aromatisation

Thanks mate that seems very reasonable. I haven't got an increase in edema, BP or water retention so far so I'll continue with the experiment and see what happens.

I guess like you said it depends on individual sensitivity. If I get my E2 to 200pmol and don't suffer the same sides as before that will settle the issue for me atleast.