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:
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.
NERD FIGHT!!
Thanks for that! A little levity is always welcome.
YES! Healthy debate is always a good thing!
I am not going to bother dealing with you taking one point and refuting with many new points that need to be responded to exponentially.
Please create a new topic, not here, and try to get guys to switch and we can see if their quality of life is any better. What else matters? That can be your contribution. You seem to have time and conviction.
I do not have time for this thread.
No need to create a new topic. This is right on topic here. I don’t feel the need to “get guys to switch”. The fact that you do betrays your mindset. People should make their own choices. I’m just trying to help them make informed vs. misinformed decisions.
Of course you don’t. You responded to my original post with what was basically a bunch of nonsense and thought that I wouldn’t be able to refute any of it. Now that I have, you want to take your ball and go home.
That’s fine, I’ve made my point and given people enough information to make an informed decision about how they want to address E2.
I am seeing some of your points but do not see that they really define a therapeutic difference. I see that you value that Exemestane is more specific than Anastrozole and that Anastrozole may be altering enzyme mediated pathways. How can you know that Exemestane has no other affects in the body? That is hard to know. You seem to refuse to acknowledge some?any of my points or twist them around, not really trying to find a mutual path of reasonable discussion. I feel that I took hours to address all of your points, you would simply create a endless flood that would not resolve anything. Meanwhile you are turning this sticky into a mess and are not interested in seeking something better in another thread where the utility of this sticky would not be trashed.
"I don’t feel the need to “get guys to switch.”
So you are not intent on getting guys onto a better protocol. What are you offering other than clutter. Take the lead and I will work with you if you can be more constructive about it.
Your hypocrisy is simply mind boggling. Look at the title of this sticky. Estradiol: Why You Should Care. Somehow, you claim that the “utility” of this sticky is being “trashed” by me posting an alternative solution to control Estradiol. Apparently you believe this sticky is your personal propaganda playground, and that anyone posting anything that runs counter to your narrative is trashing the “utility” of it which you believe is to promote your point of view and yours only. You want this to go to another thread simply because it probably won’t be seen. You are all over this forum promoting the use of Adex for E2 control. It would be impossible for me or anyone else to find all of those posts and address your error there. Hence, this sticky. The “utility” of a sticky is to address a specific topic that is common among a large number of posts. By having a sticky, you don’t have to go repeat the same thing over and over. It’s right in the sticky. Get it?
This is classic FUD (fear, uncertainty, doubt). It’s a common tactic used to sell something that has a better competitor and can’t be sold on it’s own merit. So try to introduce FUD about the superior product or service to get people to buy the inferior one. There is no other reason to ask the question. The answer can’t be known by your own admission. So it is pointless to ask. Unless you can come up with some actual objective, scientific information that it is having unwanted effects, the question is meaningless except to promote FUD. The fact that you have to resort to that to bolster your position is proof of the shaky ground that you are on.
You know, if I was betting man, I’d be willing to put real money on the bet that you’re a conservative. A classic ploy they use is to accuse others of being and doing exactly the thing that they are or are doing. As if that will somehow absolve their guilt. And that is exactly what you’ve done here. It’s obvious to anyone who has read our exchange up to this point that you are the one refusing to acknowledge the points I’ve made and that it’s you who are unable to have a reasonable discussion.
Again, by not actually posting anything instructive or constructive in response to to my post, you are trashing the sticky, not I.
I already took the lead when I first posted. And by constructive, do you mean this?[quote=“KSman, post:707, topic:104400”]
you have some kind of attitude problem. One does not increase ones dose of anastrozole, you are delusional or misinformed.
[/quote]
I suppose in your upside down world that is constructive. In the real world, it is neither constructive or reasonable.
Talk about twisting words. I said that I do not feel the need “to get” or to otherwise compel people to do anything. That is what you are trying to do. As opposed to you, I’m trying to offer useful information that people can use to make up their own minds. The only one who has offered nothing but clutter is you. Trying to defend the indefensible.
Clearly, you have some kind of agenda here. Your constant refusal to accept the contention by me and others that Exemestane is better than Adex is proof. The large number of posts by you all over this site tells me one of two things. Either A: you have no life, or B: you have some financial incentive. I’m going to go with the latter (B). This site is supported by advertising. The amount that you can ask for an Ad is based on readership. You yourself have made the observation that most people who are not having problems with their TRT don’t visit forums like this. So promote a drug that causes more problems than it’s alternative, issue FUD against that alternative, and you get more visitors which equals more Ad revenue which equals more $$ in your pocket. Perfect. For you that is. Not so much for the people you are intentionally misleading in your quest for money. This calls the integrity of this entire site into question. I’m sure that you’ve managed to actually help some people here, but that is more happenstance than by design. Give them just enough to keep them coming back, no more.
I’m done with this. Unlike you, I’m not getting paid to post here, and I’ve spent too much time on this already.
I appreciate your questioning, but your assertion that @KSman is a shill is a bit over the top. After all, the vast majority of us here, I would imagine, obtain our meds from our doctors, and it seems that almost all docs prescribe Arimidex. This thread is over 7 years old and has probably educated thousands (maybe tens of thousands) of men on the need for estrogen control, which many docs prescribing TRT today still don’t even include.
How many hours to do you think @KSman has invested in helping people on this site? I’d hate to think…it must be a pretty thankless job. Guys come here when in distress, and forget about the site when they feel great. So I imagine that he takes great pride and a lot of ownership in his stickies and his participation overall. He probably feels very needed and in demand here - perhaps that’s part of his motivation for participating.
He has definitely come off as a bit of a defensive dick in this thread, but you don’t look that much better. You are both obviously very well intelligent and have a lot to offer, and it would be great if you can both lower your shields and be more open.
Well, maybe it is. But then again, maybe it isn’t. I just don’t know how else to make sense of KSman’s hyper reactivity to any one who makes the suggestion that Aromasin may be a better alternative to Arimidex for E2 control.
Good question, but maybe the better question is, why aren’t more TRT docs prescribing it? The more I look into Aromasin, the better it sounds and I may want to try it in the future.
KP:
BTW, I did not start this sticky. And I did not invent anastrozole. I am interested in promoting aromasin if it is better. Have not seen any evidence yet that ths is generaly true from guys wearing boots on the ground. Feel free to lead me, but hitting me on the head will not be helpful. I can’t take the time right now to get deep into the material that you posted, were links there?
Tell me what you do that leads you into where you are now? Med/bio/sci background?
You have tried both anastrozole and aromasin and your personal observations are?
@KSman
I have been dissolving my anastrozole in vodka and my lab results I got today are making me question if it affects its potency.
Before my last tests I was taking .5Mg day after shot and then .5Mg 3 days after shot doing 1 shot per week of 200 MG.
Lab tests were (Taken 6 days after shot) :
Total Test-1291 Ng/Dl (247-827)
Estradiol-38.4 pg/Ml
SHBG-19 nmol/L
After that test I switched to 2 shots per wk (100 Mg each) and .7Mg anastrozole(dissolved in vodka) taken day of shot each time.
Lab test this time(Taken day of shot):
Total Test-1280 ng/dl
Estradiol-49.8 pg/ml
SHBG-21 nmol/L
I know I should be taking labs half way in between, but the dr requested this.
Also, the Anastrozole is pharma prescribed to me.