Estradiol: Why You Should Care

Low estrogen is most likely due to low testosterone. I would pressure your
endo to prescribe testosterone if your testosterone is low as well.

Thanks Receptor

My T level is 13.3 nmol

I am 30 years old and an ex propecia user of 6 years

Any help or advice would be great as my life is a living hell at present :slight_smile:

Daniel,
In regular Testosterone numbers you are at 469.74 ng/dl. A man your age should be well above that. As far as going through hell, what do you mean exactly? I need to be nosey to help you.

PM me and I will respond.

Hi KNB

I don’t if you saw above I am concerned my estrogen is low also
46 pmol/L range 99-192pmol/L

No morning wood. ED, depression, fatigue to the point I am bed bound, no memory or focus, cant play sport and I used to be a high level sports performer, cant wake up in the morning, dre eyes, any form of excercise wipes me out for days

I

Daniel,
Although it may not sound like it, you are one of the lucky men whose bodies don’t want to convert every molecule of testosterone into estrogen… I am not.
Will your doctor prescribe testosterone for you? I am willing to bet your LH and FSH numbers are really low, and that alone will cause some of the symptoms you are currently experiencing.

This is my story / labs

Please have a look and see what you can make of it?

Propecia seems to do some strange things to a mans hormones

Your help is greatly appreciated

I am currently on my first big cycle after having been on trt for quite a few years. I am just ending week 3 of taking 500 milligrams test and 600 milligrams of Primo. Within the last two days I’ve noticed that I cannot ejaculate. I can still get an erection but I cannot complete. I have gotten various suggestions about this. One has said that my E is too low and the other that it is too high. What I read is that low E can potentially create this issue. Does anyone have any suggestions? I currently take .75 anastrozole per week with this cycle breaking it up into three doses. 1 pill 24 hours after each injection

You’ll get better answers on the Pharma page.

This is not a general issue and is your case details that do not belong in a sticky, please create your own thread for this.

E2 is too high. Anastrozole dose needs to match your FT levels, so must increase with dose. Be aware that some are anastrozole over-responders, read the stickies.

Oral primo?

Suggest that you quite primo and take 4mg/week anastrozole.

My apologies on where the post landed. I wasn’t sure where to put it. The Primo is injectable not oral. I have been getting such mixed suggestions on how to react to this. You are the second person to tell me to increase anastrozole and then I’ve had two others tell me that I need to decrease it. I’m going to have some Labs taken tomorrow to see where my estradiol and my prolactin levels are right now. I’m just really confused as to how to address this.

For lab work it is important to have been on a steady dose for a while so the labs reflect reality.
Please open a new thread with the new labs.

We know from TRT work that around 1.0mg/week is needed for EACH 100mg of testosterone ester.
Advice on BB forums is often useless.

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Thank you for this information. I’ve been on trt for a long time and at my dosage, which is around a hundred and 20 milligrams a week, I have been in the normal range at .25 milligrams of anastrozole per week.

Hopefully I will have the labs sometime next week and I will definitely post them. In the meantime should I try upping the Anastrozole and see if that makes a difference?

Sounds like you’ve pinned down a good starting point for anastrozole when working with injectables.

What about transdermals? Doesn’t DHT outcompete E2? And wouldn’t that call for less use of AI?

An example:
When I was on Hcg monotherapy, my DHT was typically mid-50s ng/dL
When I’m on Androgel, my DHT is mid-90s ng/dL
In both cases, I calibrated AI to target a mid-20s pg/mL for E2.

I’m now thinking my approach to E2 was flawed. Shouldn’t I first be determining my androgen/estrogen ratio before setting a target for E2 levels?

Anyone have thoughts on this?

If high normal T is the goal, then one side of the ratio is fixed and a fixed E2=~22pg/ml goal meets that criteria.

Transdermals create more DHT in the skin than injectables.

“Doesn’t DHT outcompete E2?”
For what? DHT may occupy more SHBG and increase FT as a result. I do not see a complication.

You are free to see if you feel better with more or less E2. Make minor changes and keep dose steady for two weeks to evaluate, unless you clearly feel worse and need to bail out to a prior known dose and remember that that is a dose change that also needs an evaluation period.

Thanks. The following could be nothing more than broscience but it is what prompted my question:

> How does DHT protect against estrogen? There are at least three ways that this likely occurs. First of all, DHT directly inhibits estrogens activity on tissues. It either does this by acting as a competitive antagonist to the estrogen receptor or by decreasing estrogen-induced RNA transcription at a point subsequent to estrogen receptor binding.

At the level of gene expression, DHT competes with the influences of estrogens as does T. But I do not see any therapeutic impact of these statements.

DHT is mission critical for development of male sex organs and libido. Typically, DHT levels are good with target high-normal T levels and we do not need to worry about DHT do DHT lab work. There is a lingering concern re DHT and prostate issues that is mostly discounted now. We definitely see things go horribly wrong for some guys who take drugs to lower DHT because of male pattern baldness.

Actually, you have this totally backwards. Exemestane is taken in a larger dose, but that doesn’t mean it creates a larger burden on your body. In fact, quite the opposite. For example, I drink water by the gallon. I drink Vodka by the ounce. Using your logic, I would be better off forgoing the water and just drink Vodka because it’s taken in smaller quantities. Obviously this is wrong.

Maybe a dumb example since that’s an apple and oranges comparison.

So here is something more scientific:
2.1. Type II aromatase inhibitors

Type II aromatase inhibitors, such as aminoglutethimide, rogletimide, fadrozole, anastrozole, letrozole and vorozole, act by reversibly binding to the enzyme and by interfering with the haeme–iron group of the cytochrome P-450 moiety of the enzyme. A variety of enzymes possess cytochrome P-450 prosthetic groups, therefore, candidate inhibitors should be carefully designed in order to be aromatase-specific. Because they are reversible, ongoing oestrogen deprivation depends upon the continued presence of the drug, thus posing potential toxicity issues [13], [14] and [15].
.2. Type I aromatase inhibitors

Type I, or irreversible inhibitors (also known as suicide or mechanism-based inactivators), such as testololactone, formestane (4-hydroxyandrost-4-ene-3,17-dione (1)), exemestane (6-methylenandrosta-1,4-diene-3,17-dione (2), FCE 24304, PNU 155971), atamestane (1-methylandrosta-1,4-diene-3,17-dione (3), SH 489) and plomestane (10β-(2-propynyl)estr-4-ene-3,17-dione (4), MDL 18692) interact with the substrate-binding site of the enzyme. They must have an androstenedione-like structure and should be designed in order to be transformed by the normal catalytic action of the target enzyme into reactive species. Covalent bond formation then occurs with a nucleophilic site of the enzyme, leading to the irreversible inactivation of the target enzyme by preventing enzyme catalysis from occurring [11]. Because the inhibition is irreversible, renewed oestrogen production requires biosynthesis of new enzyme aromatase [15]. This would result in reduced side effects when the inhibitor is used as a drug, since the inhibitor’s effect can persist after its clearance from the system and the continuing presence of the drug to maintain inhibition is thus not necessary.

Source:Exemestane, a new steroidal aromatase inhibitor of clinical relevance - ScienceDirect

So as you can see, Aromasin (exemestane) actually decreases the body burden.

As for cost, there isn’t much of a difference when buying it as a research chemical. I do quite well taking 6.25MG every three days. I get a bottle of 30ML at 25MG per ML for about $70. At my dose, this lasts about a year.

Really not very expensive. Plus, you don’t get any of the sides such as joint pain, lowered HDL etc.

Also, since Anastrozole merely inhibits Aromatase rather than “using it up” like Exemestane, you will constantly be making more aromatase which will just keep building up in your body which is a very unnatural state. So you will need keep increasing your dose of anastrozole to keep up creating even more toxic build up of the drug.

I’ll stick with Aromasin.

I was simply pointing out that there was less mg’s if drug for the liver to metabolize and kidneys to excrete. Some care about these things and you do not.

“Exemestane is taken in a larger dose” - that is what I said, if you care to read again. “What is so great about “suicidal AI” when you need to take so many mg’s compared to 1mg/week with Arimidex/anastrozole?”

You cite good info. But your logic falls on its face when you look at the quantities required. Exemestane is 90% protein bound [VS 40%], great drug perhaps, delivery is inefficient. The molar masses are almost identical, so the number of molecules per mg is not a factor. mg per mg, anastrozole is more effective and more cost efficient in may contexts. And Exemestane has simply failed in some cases here where guys have tried both.

You are citing side effects from breast cancer use where the goals is E2=zero and also from forums where people have taken E2 very low. The TRT goals that I recommend are E2=22pg/ml - 80 pmol/L and at that level, that of many young lean males, joint pain and lipid disturbances simply do not typically occur. There are a few rare cases where guys react abnormally to anastrozole, and one always has to be alert to cases where one is not dealing with normal responses. There are always some odd differences that are probably all differences in enzymes, caused by genetic variations or materialization mediated changes in gene expression [epigenetic].

This also a deeply flawed comment. If Exemestane is using it up, why are so many more molecules of it required? Anastrozole simply works better and you have some kind of attitude problem. One does not increase ones dose of anastrozole, you are delusional or misinformed. Enzymes are constantly been recycled and replaced. If otherwise, one dose of Exemestane would last forever.

In any case, we simply do not generally see guys reporting that they switched to Exemestane from anastrozole and feel better.

Where to begin with this word salad? Lets start here :

Why would you assume that I don’t care? My entire point was that Exemestane is LESS TOXIC, which why I have chosen it. It is clearly stated in my post. The parts that you conveniently left out.

Here: Because Type II aromatase inhibitors are reversible, ongoing oestrogen deprivation depends upon the continued presence of the drug, thus posing potential toxicity issues [13], [14] and [15].

And here: Type I or irreversible inhibitors: Because the inhibition is irreversible, renewed oestrogen production requires biosynthesis of new enzyme aromatase [15]. This would result in reduced side effects when the inhibitor is used as a drug, since the inhibitor’s effect can persist after its clearance from the system and the continuing presence of the drug to maintain inhibition is thus not necessary.

Apparently, you couldn’t be bothered to actually read this part, but instead reacted with the same knee jerk response you do any time you see someone advocating the use of Aromasin over Arimidex.

You then go on to ask the same rhetorical question

The answer is clearly stated above.

Now for this:

So? Do you even understand the ramifications of this? Unbound drugs are going to be more toxic than bound drugs. They must be metabolized.
Hepatic metabolism accounts for approximately 85% of anastrozole elimination. And you also seem to be ignoring that Steady-state plasma levels are approximately 3-to 4-fold higher than levels observed after a single dose of ARIMIDEX. With a terminal half life of 50 hours and a constant buildup of the drug, your liver is going to be doing a lot of work at all times eliminating it. Exemestane on the other hand has a half life of 24 hours and following repeated daily doses of exemestane 25 mg, plasma concentrations of unchanged drug are similar to levels measured after a single dose.
And that’s at 25mg a day, a much larger dose than we need for our purposes. So lets see, a drug that you must continually metabolize or one that is in you body for a day. It seems that Anastotrozole is exactly the opposite of what you claim and you are the one who isn’t bothered by having your liver and kidneys constantly woking on something foreign. You are simply helping me make my point here.

And this is just more nonsense:

Huh? This is clearly just a poor attempt at obfuscation. It is utterly meaningless.

I said “Also, since Anastrozole merely inhibits Aromatase rather than “using it up” like Exemestane, you will constantly be making more aromatase which will just keep building up in your body which is a very unnatural state.” Perhaps “using it up” was a poor choice of words. I was trying to state it in a way that a less sophisticated person would understand. Apparently, it just confused you. A more proper way of stating would be permanent deactivation. This means that Exemestane binds irreversibly to and inhibits the enzyme aromatase. Got it? Then you said

This question really makes me wonder about your cognitive abilities.
This is what’s known as circular logic. And one has to ask, so many more molecules than what? Anastrozole? They are both doing two completely different things.
The end result is the same, but they both use completely different mechanisms to achieve it. You can’t compare one to other on a molecule to molecule basis. Again a meaningless statement that itself falls flat. If that doesn’t convince (actually I doubt anything will convince you, but the more reasonable readers here will benefit) here’s a little tidbit:

The two nonsteroidal AIs, letrozole and anastrozole, at concentration as low as 8 nmol/L, caused an increase of aromatase protein levels. These results were expected because letrozole and anastrozole bind to aromatase with high affinities that stabilize the structure of aromatase protein. However, it was not expected that the steroidal inhibitor, exemestane, in contrast, caused a reduction of the aromatase protein. Source:http://cancerres.aacrjournals.org/content/66/21/10281.long

See that? Your drug of choice causes an increase in Aromatase, whereas Exemestane causes a decrease. Just like I said. Nothing “deeply flawed” about it. And that increase is going to require an equal increase in the dose of anastrazole. I am neither delusional nor misinformed. In fact, I’ve seen posts of yours where you admit to this exact phenomena, but just dismiss it as inconsequential. Perhaps your memory is faulty. Mine is not.

Then this last whopper

Where exactly did I state anything different?[quote=“KSman, post:707, topic:104400”]
Anastrozole simply works better and you have some kind of attitude problem.
[/quote]

Ever heard of projection? But you’re right about that last part part. I don’t suffer fools easily.
I see post after post here by men complaining about the sides from Arimidex. If it works so well, why are so many complaining about? And it’s not “epigenetic”. Do you even know what that means? Throwing around terms like that may impress the less sophisticated reader, but to the rest of us, it just makes you look like a crackpot.
You keep beating this meme that less is better like a dead horse. It’s the pillar upon which your entire argument rests. But it’s a pillar made of sand and is easily knocked down. Actually, the fact that Adex is taken in such small quantities is precisely what makes it so difficult to work with. If you take an extra milligram or two of Aromasin, it’s not going to make you sick for days or even weeks as is the case with the AI you’re pushing everyone to take. With Aromasin, there is a much larger margin for error. You’re doing every man here a great disservice by telling them to take Adex as their fist line of defense against excess E2 and dismissing Exemestane (Aromasin) as just pseudo “broscience”. It’s obvious to anyone reading your posts that you have some kind of axe to grind with the weightlifters. The reality is it’s because of their pioneering use of AAS that we know as much about TRT that we do now. I think we owe them a debt of gratitude, not derision.
So to anyone else reading this, do your own research and come to your own conclusions. Don’t just take the word of some random guy on the internet who sets himself up as some kind of expert. Especially one wth an axe to grind.

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NERD FIGHT!!

:joy: