Dr. Eugene Shippen on estradiol, aromatization...

[Gman86]

Not sure if women having higher estrogen levels is the reason they have an increased risk for Alzheimer’s. Alzheimer’s is basically caused by two main factors, from my understanding. Insulin resistance, and neurons in the brain becoming damaged. Alzheimer’s/ dementia are basically called type 3 diabetes at this point. Testosterone, as far as I know, is one of the most important things to maintain insulin sensitivity. Almost every diabetic male will have low testosterone levels. It’s possible that older women having even lower testosterone levels than older men could increase their risk of becoming insulin resistant, and therefore increase their risk for Alzheimer’s. The other reason that women might be at a higher risk is because they frequently are low in b12. Low b12 is much more common in women than in men. B12 is extremely important in regards to neuron health. Part of the reason is because without b12, the myolin sheath that protects these neurons starts to deteriorate, and the neurons start to become damaged, and this can eventually lead to brain diseases like Alzheimer’s/ dementia.

As far as estrogen increasing autoimmune diseases, I’m not sure. I haven’t done much research in regards to the correlation between the two.

 

[lowe2sucks]

might be also that women live longer than men to get those diseases?

 

[Gman86]

He could claim that since testosterone levels have been falling for decades now, these estradiol numbers are all sub-optimum.

That is a good point. I thought of this as well. And it could be true, young males might of had higher levels of E2 say 100 years ago or more. But I still don’t think it would be in the 60-80 range. If now the upper end is roughly around 35-45, I think 100 years ago the top end MIGHT of been around 45-55. And again, that’s the top end of the range. Most guys when they were in their prime would not fall in the top end of the range.

 

[Gman86]

might be also that women live longer than men to get those diseases?

Oooo, good point. Didn’t even consider that factor.

 

[JimBob]

Women get a lot more autoimmune diseases than men, estrogen is thought to be the cause these immune diseases.

You can google autoimmune and estrogen. Also estrogen dominance.

Not sure if estrogen is the reason women get alzheimer's more often than men, at age of 65, women have a 1 in 6 chance of developing Alzheimer’s, compared to a 1 in 11 chance for men.

It's natural that estrogen would decline with age in men because estrogen in men is derived from testosterone. While estrogen declines a little with age, testosterone declines a lot more.

By the time a woman hits 65, her estrogen is low, and she becomes susceptible to Alz. If estrogen caused Alz, young women would get it since their estrogen is normal/high.

 

[Vince Carter]

By the time a woman hits 65, her estrogen is low, and she becomes susceptible to Alz. If estrogen caused Alz, young women would get it since their estrogen is normal/high.

To that same line of thought, you can go to a young male with high levels of DHT and they don't have Prostate problems. Such as in your example women going low E, men conversely do go with higher levels of E and it's there that you see these problems, like Prostate, start to show up. Amongst other male problems, prostate just being an example.

 

[Dr. John Crisler]

Thanks for the response, and agree completely. Really wish there were studies done, ON MEN, that looked at the potential consequences of high E2, and more importantly, determined where the upper cutoff is to where the side effects outweighed the benefits. Because we obviously already know there is negative consequences to any hormone being in excess, so we don’t need a study to tell us that E2 at too high of a level is going to cause issues. We just need to know what issues it can cause, and the upper range that they found where the side effects began to outweigh all the benefits of E2, in most of the test subjects.

But we all pretty much know that we shouldn’t be holding our breath for any studies like this, unfortunately. So in the meantime, I think we all just need to be getting our free E2 done, and reporting our results in regards to mood, libido, erection quality, etc. Yes, this isn’t as good as a study, where they can hopefully tell us objective things like where does E2 stop being cardiovascular protective, and start potentially increasing your cardiovascular risk, but it’s all we can do while we wait for studies on high E2 in men to be done.

And yes, cost is a huge factor, I understand, but I still hope more guys start testing for it. Even if they do it once every 3rd or 4th time they get labs done. And hopefully the cost of the test comes down in the future.

Well thought out, and said.

There are no studies, to my knowledge, showing very high estrogen (and/or DHT) levels are safe in adult men; much less where optimal benefits are to be found.

All the studies I have seen just show what we already knew: driving estrogen too low is always bad. This is taking into account the vast majority of them used the invalid immunoassay technology.

....but we can eyeball roughly what the Free E2 is, knowing total E2 and SHBG.

 

[Gman86]

Well thought out, and said.

There are no studies, to my knowledge, showing very high estrogen (and/or DHT) levels are safe in adult men; much less where optimal benefits are to be found.

All the studies I have seen just show what we already knew: driving estrogen too low is always bad. This is taking into account the vast majority of them used the invalid immunoassay technology.

....but we can eyeball roughly what the Free E2 is, knowing total E2 and SHBG.

And what I hope to do by continuing to post my total E2, free E2, and SHBG, every time I get labs done, is to allow people to find a calculator that appears to be the most accurate. They can look at each set of my labs, take my total E2 and SHBG, run both numbers through the calculator, see what they get, and then have my actual free E2 to compare to and see how accurate the calculator is. Until everyone is getting their free E2 done, like we all get free T done now, the calculated method should be fairly accurate, I would imagine.

 

[jhperez81]

There is a calculation. It uses the same formula that the free testosterone calculator uses only the binding affinity constants for SHBG and Albumin are different for E2.

 

[Gman86]

There is a calculation. It uses the same formula that the free testosterone calculator uses only the binding affinity constants for SHBG and Albumin are different for E2.

Oh ya, I keep forgetting about albumin. I should post that, as well, with my total E2, free E2 and SHBG. Thanks

 

[jhperez81]

This is the study where they calculated free E2 from Total E2. I couldn’t figure it out but maybe someone smarter than me can figure it out. Look on page 2 middle column. http://care.diabetesjournals.org/content/diacare/early/2011/06/23/dc11-0208.full.pdf

 

[Vince Carter]

This is the study where they calculated free E2 from Total E2. I couldn’t figure it out but maybe someone smarter than me can figure it out. Look on page 2 middle column. http://care.diabetesjournals.org/content/diacare/early/2011/06/23/dc11-0208.full.pdf

Ugh...math is my worst subject

 

[SkiDaddy]

Will someone please explain in detail what knowing your Free E2 can do for you and how it relates to SHBG and E2 Sensitive.
Example here are my recent labs. please comment.

Free Serum Estradiol, Serum, MS 16 pg/mL 01 Reference Range: Adult Males: 8.0 - 35
Percent 2.2 % 01 Reference Range: Adult Males: 1.7 - 5.4
Free Estradiol, Serum 0.35 pg/mL 01 Reference Range: Adult Males: 0.2 - 1.5
E2 Sensitive = 8 Range 8-35
SHBG = 39.9
Total Testosterone = 900

 

[Gman86]

Will someone please explain in detail what knowing your Free E2 can do for you and how it relates to SHBG and E2 Sensitive.
Example here are my recent labs. please comment.

Free Serum Estradiol, Serum, MS 16 pg/mL 01 Reference Range: Adult Males: 8.0 - 35
Percent 2.2 % 01 Reference Range: Adult Males: 1.7 - 5.4
Free Estradiol, Serum 0.35 pg/mL 01 Reference Range: Adult Males: 0.2 - 1.5
E2 Sensitive = 8 Range 8-35
SHBG = 39.9
Total Testosterone = 900

Free E2 is the amount of E2 that is active and stimulating estrogen receptors. Basically it’s the amount of E2 that’s actually doing anything. The total serum level is the total amount in your blood, but that doesn’t mean too much. It’s the amount that’s active that you want to really focus on. Same concept with free vs total testosterone, and free vs total T3.

SHBG is a protein that binds to hormones, like E2, for example. The higher the SHBG level, the more bound your E2 is going to be. So if you had two people with the same total E2 level, and one had a high SHBG, and the other a low SHBG, the person with the high SHBG will have less free E2 because it is mostly bound and useless. Only free E2 is what is stimulating estrogen receptors, the rest that is bound is literally doing nothing. The person with the low SHBG will have less that is bound, and more that is active to stimulate estrogen receptors.

So in your case, your total E2 is low, and your free E2 is on the low side. But someone else with a very low SHBG might have a free E2 in the middle of the range with your total E2 level. So it’s just good to check free E2 as well as total. Just getting total E2 done leaves you guessing a little bit as to how much active free E2 you have stimulating estrogen receptors.

 

[SkiDaddy]

So would it be better for me to have a higher E2 and higher Free E2 as related to health and libido?

 

[Tgrappler]

I'm just really grateful for all the information provided here. If there's anything to say is that TRT must include E2 management strategies and not just a prescription for an AI.
From personal experience I can assure anyone that crashed estradiol levels are one of the worst things you can experience. From all the research I've done there's no way to "crash" your E2 to such low levels as with a pharmaceutical AI. The point is extremely low estradiol is dangerous and your body will fight desperately to bring it back to some reasonable level. I presume it's possible to have naturally low E2, but it's nothing like an "artificial" crash.

Elevated E2 isn't great either, but it's an entirely different worlds of symptoms and managing those is by far easier than trying to recover from a crash.
Likewise my T levels have bounced from 200 to over 1700 (tested at the peak) and I have never experienced severely debilitating symptoms, like I did when my E2 fell dangerously low.

Try to avoid AI at all costs and if you do take it, use the smallest dosage possible and take it as rarely as possible.

I suspect that for many people a significant drop in E2, which happens very quickly due to AI can be extremely unsettling. Even if it brings you back to normal levels the rapid drop requires for the body to adjust... I do not believe that E2 can naturally variate by 20-30 points in one day. AI will foce you into a very unnatural state of being.
Again, personal experience. Proceed with caution.

 

[Simon7]

FYI, I just posted a new thread with a spreadsheet to calculate Free E2 based on Total E2, Albumin and SHBG. Welcome to use it!

 

[Dr. John Crisler]

We mostly ignore total T, total T4, total T3 when managing hormones so why don’t we ignore Total E2? After all it’s the free active hormone that really matters right?

We don't usually test Thyroid Binding Globulin, as we do SHBG.

 

[Dr. John Crisler]

the one thing i cannot understand with keith nichols is the fact that he says young men have raging estradiol levels. I have seen young men's blood tests and this is not the case. As well as for myself at age 25. What is your experience Doctor Crisler seeing men with healthy testosterone in their teens and twenties, is estradiol also elevated or usually normal?

I only run the valid LC/MS Estradiol assay, and do not see it above range.

 

[Dr. John Crisler]

estradiol protects against alzeimhers stop this estrogen dominance bullshit please
low estrogen is risk factor for alzeimers
estradiol alzeimers - Google Search
AIs induce memory and cognitive problems and what AIs do? block aromatase thus lower testosterone > estradiol conversion

That has been shown in every study looking at it in men so far. But what did every study do? Use, for instance, a milligram of anastrozole per day. A milligram a week is a fairly substantial dose for a man on TRT. Why would we use studies where they administered 7 times too much of a drug? Any drug.