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Thread: Exemestane-The Underdosed AI

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    Exemestane-The Underdosed AI

    Ok so let me start off by saying there have been some great threads and great discussions and contributions recently. One that particularly caught my attention was the Aromasin thread started by Mickey. It was particularly of interest because I had been doing a lot of research on exemestane at that very time.

    Its important when we look at AI's and data from studies etc its important that we use data on males. There are several key differences in an ai's effects in men and women. First and foremost is they are more effective in women at reducing estrogen. Second is they have a much longer half life in women than they do in men. Very often people misquote how much an ai will reduce estrogen based on data taken from a study on females. So when you look at studies on ai's,on males you find one thing out very quickly. There are plenty available on anastrozole and letrozole and there is essentially 1 with all inclusive data on exemestane. Luckily that one holds some very solid and applicable data for our purposes.

    Key Points of Study:

    1- Take Exemestane with dietary fats. They administered it this was in this study, referencing another study which showed an increase in the absorption of exemestane of 40% when taken with fats.

    2- Exemestane administered at25mg/day vs 50mg/day offered minimal difference in estrogen levels. While the 50mg/day lowered levels more quickly both dosages ultimately ended up at virtually the same estrogen levels. I suspect the increased androgens of a cycle might alter this slightly and a slight more of a difference would be observed with 50mg/day over 25mg/day it is very obvious that 25mg/day is the optimal therapeutic dose for this drug.

    3- Exemestane had either no negative effect or a positive effect on igf and lipids at either dose (25 or 50mg/day). Its interesting in and of itself something that lowers estrogen can have no impact on these things, the fact that there is a positive impact is pretty amazing.

    4- Exemestane had a dramatic effect in reducing estrogen, but at both 25mg/day and 50mg/day while estrogen levels were low they were within the clinical range. So it is VERY difficult to "crush"estorgen levels with exemestane. This is huge as anyone that has experienced this with letrozolle or anastrozole will tell you it is no picnic and it is also very unhealthy as well.

    5- Exemstane exhibits a half life in males between 8-9hrs. Because of the way ot works this is not indicative of the effective time of the drug. However it is worth paying attention too - something i have previously dismissed.


    So based on my personal experience with exemestane, and all the things I read above, all the under dosed stane posts i see across the various forums, and some great discussions here, I had come to the conclusion that we are dosing exemstane too low. We have a compound here with a clear optimal therapeutic dosage of 25mg. It will lower your estrogen levels but not crush them even at a high dose. It has a positive or no effect on the normal areas of concern when lowering estrogen like igf and cholesterol. It has a very short half life.

    We have a study here of males not taking testosterone , where they are taking 25-50mg/day and keeping estrogen levels low but within the clinical range. That is our exact goal! As I looked at this more and more it became apparent to me that my thoughts on dosage and administration frequency were in fact incorrect, Not only were they thoughts I subscribed too, but ones that are widely subscribed too. Why would we take less than these males when we have more androgens present? It makes no sense.Well in my opinion the answer is we shouldn't be. I decided I was going to be a guinea pig myself and play with exemestane dosages and get blood work my next cycle. I had become convinced and speculated the optimal protocol for my cycle,which would consist of a test base of 500mgs/week, would be 25mgs of exemestane/day. Broken up into 2 - 12,5 mg doses taken with fats.

    Now had I not been browsing the various forums today I wouldn't be posting this. I came across a post of bloodwork from a gentleman, on cycle, 500mgs test/week , taking 25mgs exemestane per day, in 2 -12,5 mg doses with meals and his estrogen levels were safely within reference range!

    That pretty much sealed it for me. I seriously think we are taking too little exemestane. I am going to do blood work when I go on cycle but at this point I dont think this is speculation. The study data backs it. The real world data backs it (good and bad), and you have a drug even at high doses that offers nothing in the way of traditional negative effects when lowering estrogen, positively impact some of those effects, and is very difficult to crash estrogen levels when taking.

    I firmly believe that an increase in dosage and frequency of administration combined with taking with dietary fats will improve the effectiveness of exemestane. I really do believe that is the proper dose, taken in the proper way to ensure maximal effectiveness. It has taken some time for me to evolve this opinion and much discussion with some great guys here. Always learning.

    Anyway I wanna Hear your guys thoughts on this. Oh and here is the study reference : Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

    ps- Special thanks to Mickey Knox and all those who participated in that Aromasin and several related threads. There are too many people too mention new and old members all made great contributions.

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    I was under the understanding that aromasin can only reduce estrogen 50-60 %? So for instance if a person is on cycle and they e levels without administering aromasin were 400. The most they could be reduced to are 240 using aromasin. Now this is not perfect math but just a close guess. Any thoughts? Basically my understanding is the same. You cannot crush your E using aromasin
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    Outstanding contribution, Jimmy. Thank you.
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    Good read thanks
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    Quote Originally Posted by jim230027 View Post
    I was under the understanding that aromasin can only reduce estrogen 50-60 %? So for instance if a person is on cycle and they e levels without administering aromasin were 400. The most they could be reduced to are 240 using aromasin. Now this is not perfect math but just a close guess. Any thoughts? Basically my understanding is the same. You cannot crush your E using aromasin
    The not crushing estrogen part or being very difficult too I believe. The reason we (or I ) cant definitively say the other Jim is that we dont know if that holds true with the high levels of test when on cycle. The exogenous introduction of test and resulting effects on amount af aromatase make it impossible to say the % will be or stay the same. Its easy when thats the case in a very limited window of people with test levels in clinical range. The whole game may change when you have 6x the amount of testosterone so I cant 100% get behind that percentage theory. I do see why people think it though.
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    clarky. is offline MONITOR
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    Great post.
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    Great information. Thank you for posting!
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    this is a dam good post jimmy thank you for your insight and nice work...ohh and you suck, you made my push the like button damit!!
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    Nice one Jimmy.

    I 100% agree based on personal experience and bw but it's nice to know the how and why....
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    Quote Originally Posted by ghettoboyd View Post
    this is a dam good post jimmy thank you for your insight and nice work...ohh and you suck, you made my push the like button damit!!
    lol sorry buddy

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    Quote Originally Posted by Sgt. Hartman View Post
    Nice one Jimmy.

    I 100% agree based on personal experience and bw but it's nice to know the how and why....
    Actually I could have cited you as a ref as your personal experience played a part in helping solidify my line of thinking.
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    calstate23 is offline Banned
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    I kind of skimmed through but also another plus is unlike binding AI's (Adex) you will not get estrogen rebound....As Aromasin will destroy the aromatase enzyme...
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    Another great informative post.

    Thanks Jimmy
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    Very nice post jimmy!
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    Can anyone tell me if they have Heard of "Xtreme Pharma" from uk, I have bought some of their stuff and now im hearing bad things about them. Does anyone know if they are legit or not????

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    Quote Originally Posted by jimmyinkedup View Post
    Ok so let me start off by saying there have been some great threads and great discussions and contributions recently. One that particularly caught my attention was the Aromasin thread started by Mickey. It was particularly of interest because I had been doing a lot of research on exemestane at that very time.

    Its important when we look at AI's and data from studies etc its important that we use data on males. There are several key differences in an ai's effects in men and women. First and foremost is they are more effective in women at reducing estrogen. Second is they have a much longer half life in women than they do in men. Very often people misquote how much an ai will reduce estrogen based on data taken from a study on females. So when you look at studies on ai's,on males you find one thing out very quickly. There are plenty available on anastrozole and letrozole and there is essentially 1 with all inclusive data on exemestane. Luckily that one holds some very solid and applicable data for our purposes.

    Key Points of Study:

    1- Take Exemestane with dietary fats. They administered it this was in this study, referencing another study which showed an increase in the absorption of exemestane of 40% when taken with fats.

    2- Exemestane administered at25mg/day vs 50mg/day offered minimal difference in estrogen levels. While the 50mg/day lowered levels more quickly both dosages ultimately ended up at virtually the same estrogen levels. I suspect the increased androgens of a cycle might alter this slightly and a slight more of a difference would be observed with 50mg/day over 25mg/day it is very obvious that 25mg/day is the optimal therapeutic dose for this drug.

    3- Exemestane had either no negative effect or a positive effect on igf and lipids at either dose (25 or 50mg/day). Its interesting in and of itself something that lowers estrogen can have no impact on these things, the fact that there is a positive impact is pretty amazing.

    4- Exemestane had a dramatic effect in reducing estrogen, but at both 25mg/day and 50mg/day while estrogen levels were low they were within the clinical range. So it is VERY difficult to "crush"estorgen levels with exemestane. This is huge as anyone that has experienced this with letrozolle or anastrozole will tell you it is no picnic and it is also very unhealthy as well.

    5- Exemstane exhibits a half life in males between 8-9hrs. Because of the way ot works this is not indicative of the effective time of the drug. However it is worth paying attention too - something i have previously dismissed.


    So based on my personal experience with exemestane, and all the things I read above, all the under dosed stane posts i see across the various forums, and some great discussions here, I had come to the conclusion that we are dosing exemstane too low. We have a compound here with a clear optimal therapeutic dosage of 25mg. It will lower your estrogen levels but not crush them even at a high dose. It has a positive or no effect on the normal areas of concern when lowering estrogen like igf and cholesterol. It has a very short half life.

    We have a study here of males not taking testosterone , where they are taking 25-50mg/day and keeping estrogen levels low but within the clinical range. That is our exact goal! As I looked at this more and more it became apparent to me that my thoughts on dosage and administration frequency were in fact incorrect, Not only were they thoughts I subscribed too, but ones that are widely subscribed too. Why would we take less than these males when we have more androgens present? It makes no sense.Well in my opinion the answer is we shouldn't be. I decided I was going to be a guinea pig myself and play with exemestane dosages and get blood work my next cycle. I had become convinced and speculated the optimal protocol for my cycle,which would consist of a test base of 500mgs/week, would be 25mgs of exemestane/day. Broken up into 2 - 12,5 mg doses taken with fats.

    Now had I not been browsing the various forums today I wouldn't be posting this. I came across a post of bloodwork from a gentleman, on cycle, 500mgs test/week , taking 25mgs exemestane per day, in 2 -12,5 mg doses with meals and his estrogen levels were safely within reference range!

    That pretty much sealed it for me. I seriously think we are taking too little exemestane. I am going to do blood work when I go on cycle but at this point I dont think this is speculation. The study data backs it. The real world data backs it (good and bad), and you have a drug even at high doses that offers nothing in the way of traditional negative effects when lowering estrogen, positively impact some of those effects, and is very difficult to crash estrogen levels when taking.

    I firmly believe that an increase in dosage and frequency of administration combined with taking with dietary fats will improve the effectiveness of exemestane. I really do believe that is the proper dose, taken in the proper way to ensure maximal effectiveness. It has taken some time for me to evolve this opinion and much discussion with some great guys here. Always learning.

    Anyway I wanna Hear your guys thoughts on this. Oh and here is the study reference : Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

    ps- Special thanks to Mickey Knox and all those who participated in that Aromasin and several related threads. There are too many people too mention new and old members all made great contributions.
    Good job Jimmy
    jimmyinkedup likes this.

  17. #17
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    I was waiting for this great info!!

    Jimmy from what I understand according to you research even when on a low dose test or even TRT levels along side non aromatizing compounds a 25mg ed protocol should not crash estrogen correct? Just double checking
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    Good research looking forward to the self clinical trial results.
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    Everyone is different because everyone produces aromatase enzyme at different rate and gh also increases this rate....

    Most likely, you will see you will need less as you continue on your protocol....

    On smaller cycles I've done...25 mg 2-3 days..Sometimes less....

    But always need less as cycle progresses.....

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    Great info
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    Shit!!!! Now I'm gonna have buy another box of aromasin . Thanks. hahaha
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    Hi Jimmy,

    First of all, great post brother. I always enjoy reading your opinions and ideas. They’re thought provoking and inspiring at the same time. And secondly, thank you for the acknowledgment at the end of your post.

    The study you are quoting, “Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males”, is the same study I quoted in my Aromasin vs Arimidex article – I highlighted it in bold and provided similar details as this post. The reason I bring this up is because firstly, I want to share the reason I choose not to subscribe to the 25mg/day on cycle. And secondly, ask your thoughts and opinion on this issue.

    Although it’s clear I support the fact that Aromasin was/has been administered too low in the past, otherwise I wouldn’t have written the Aromasin vs Arimidex article in the first place - my concern is that the study you’re referring to in order to support 25mg/day on an average AAS cycle, was conducted for only 10 days. If you look at the E2 graph in the study you provided you will notice the baseline is around 28pg/mL, but only ten days later the serum levels show a value of approximately 18pg/mL. This suggests to me that Estrogen levels are declining and will *likely continue to decline if the 25mg/day administration/protocol is continued. In fact, the study ends with a conclusion and proper caution that is often attached to inconclusive short term studies, *“Long-term efficacy and safety will need further study.” However, this is certainly not etched in stone and only my hypothesis based on this study, details of past AAS users, and my use of Aromasin.

    And since there is no “long term” study available for us to review, my opinion and recommendation is still 12.5mg/day to begin and then monitor from there. This is why I did not quote those particular facts of this aforementioned study that we have both cited. I left it up to the reader to draw their own conclusions based on the information contained in the study and their personal experience, if any, to rely on based upon how sensitive they are to Estrogen fluctuations – as we all know too well, everyone is different. So at best, it’s very difficult to pigeon hole a extremely large diverse group into one protocol. So i decided to error on the side of caution - not suggesting that you aren't, im simply attempting to make clear my own assertions.

    For the record, I am certainly not attempting to disparage or discredit your opinion. On the contrary, I always look forward to reading your ideas, thoughts, and opinions as they are most always backed up with supporting data. My intentions are only to properly debate this issue with supporting information as you have done, and I have as well. And I know from past experience that you and I are on the same page in terms of up to date and accurate information, along with the health and safety being our goal and number one priority. So I appreciate and respect your ideas and contributions Jimmy.

    And finally, I’m puzzled why an HRT Specialist would feel this is “outstanding” given the information here is simply a summary of a study and perhaps some conjecture. Although I completely agree that Jimmy’s post is very well written – as all his posts and comments are - and the clinical study is a step in the right direction. But what exactly is outstanding about it? I don’t mean to center you out Austin, but you’re the only HRT Specialist that commented so far and would like your opinion or at least clarification. Much appreciated.

    And if you could, Austin, comment on the following piece of data from the above mentioned study that IMHO is of particular significance. “The mean baseline levels of estradiol and testosterone were 24.5 8.8 pg/ml and 581 165 ng/dl, respectively. Maximal suppression of estradiol (62 14%) was observed 12 h after a single 25-mg dose of exemestane. Estradiol remained suppressed by 58 21% at 24 h and returned to baseline 3–6 d after treatment

    Just want to clear and ensure that I have complete coverage and learn together. Again, thanks in advance Austin. And thank you Jimmy!

    Respect,
    Mick.
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    Awesome post. I tried aromasin for an AI on my last cycle @ 12.5 mgs eod and couldn't figure out why the sides started to slowly creep up on me towards the end of the cycle. I am glad between yourself and Mickey that some light has been shed on this. Thank you.

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    Quote Originally Posted by Buster Brown View Post
    Awesome post. I tried aromasin for an AI on my last cycle @ 12.5 mgs eod and couldn't figure out why the sides started to slowly creep up on me towards the end of the cycle. I am glad between yourself and Mickey that some light has been shed on this. Thank you.
    EOD protocols for Aromasin are simply not frequent enough with the very short 9 hour half life. Glad to hear you're managing your E2 properly.
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    does that mean i should switch to letro ?
    or simply switch from 12.5mg ED to 25mg ED ?
    thats scary
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    Quote Originally Posted by largerthannormal View Post
    I was waiting for this great info!!

    Jimmy from what I understand according to you research even when on a low dose test or even TRT levels along side non aromatizing compounds a 25mg ed protocol should not crash estrogen correct? Just double checking
    thats a good question. im interested in knowing the answer as well
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    Thanks for this Jimmy. I was about to toss a new bottle of aromasin after reading a recent post which showed bloodwork with elevated estro while on aromasin. A quick google search shows alot of different people are posting high estro with it, but almost all are either using 10 or 12.5mg eod or ed.
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  28. #28
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    I just started stane a week ago from adex. Ill get blood in a couple weeks and throw it up in here to.
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    Quote Originally Posted by Granovich View Post
    does that mean i should switch to letro ?
    or simply switch from 12.5mg ED to 25mg ED ?
    thats scary
    Id give 25mg ed a go first, though I personally love the letro and use that mostly (at about 0.25mg eod-e3d, sometimes a wee bit more if higher dosed cycle)


    awesome post for sure though, will prob try 25mg ed-eod on my high end hrt and see how that is after a few weeks.
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    Quote Originally Posted by largerthannormal View Post
    I was waiting for this great info!!

    Jimmy from what I understand according to you research even when on a low dose test or even TRT levels along side non aromatizing compounds a 25mg ed protocol should not crash estrogen correct? Just double checking
    I believe this to be the case - yes.

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    Quote Originally Posted by MickeyKnox View Post
    Hi Jimmy,

    First of all, great post brother. I always enjoy reading your opinions and ideas. They’re thought provoking and inspiring at the same time. And secondly, thank you for the acknowledgment at the end of your post.

    The study you are quoting, “Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males”, is the same study I quoted in my Aromasin vs Arimidex article – I highlighted it in bold and provided similar details as this post. The reason I bring this up is because firstly, I want to share the reason I choose not to subscribe to the 25mg/day on cycle. And secondly, ask your thoughts and opinion on this issue.

    Although it’s clear I support the fact that Aromasin was/has been administered too low in the past, otherwise I wouldn’t have written the Aromasin vs Arimidex article in the first place - my concern is that the study you’re referring to in order to support 25mg/day on an average AAS cycle, was conducted for only 10 days. If you look at the E2 graph in the study you provided you will notice the baseline is around 28pg/mL, but only ten days later the serum levels show a value of approximately 18pg/mL. This suggests to me that Estrogen levels are declining and will *likely continue to decline if the 25mg/day administration/protocol is continued. In fact, the study ends with a conclusion and proper caution that is often attached to inconclusive short term studies, *“Long-term efficacy and safety will need further study.” However, this is certainly not etched in stone and only my hypothesis based on this study, details of past AAS users, and my use of Aromasin.

    And since there is no “long term” study available for us to review, my opinion and recommendation is still 12.5mg/day to begin and then monitor from there. This is why I did not quote those particular facts of this aforementioned study that we have both cited. I left it up to the reader to draw their own conclusions based on the information contained in the study and their personal experience, if any, to rely on based upon how sensitive they are to Estrogen fluctuations – as we all know too well, everyone is different. So at best, it’s very difficult to pigeon hole a extremely large diverse group into one protocol. So i decided to error on the side of caution - not suggesting that you aren't, im simply attempting to make clear my own assertions.

    For the record, I am certainly not attempting to disparage or discredit your opinion. On the contrary, I always look forward to reading your ideas, thoughts, and opinions as they are most always backed up with supporting data. My intentions are only to properly debate this issue with supporting information as you have done, and I have as well. And I know from past experience that you and I are on the same page in terms of up to date and accurate information, along with the health and safety being our goal and number one priority. So I appreciate and respect your ideas and contributions Jimmy.

    And finally, I’m puzzled why an HRT Specialist would feel this is “outstanding” given the information here is simply a summary of a study and perhaps some conjecture. Although I completely agree that Jimmy’s post is very well written – as all his posts and comments are - and the clinical study is a step in the right direction. But what exactly is outstanding about it? I don’t mean to center you out Austin, but you’re the only HRT Specialist that commented so far and would like your opinion or at least clarification. Much appreciated.

    And if you could, Austin, comment on the following piece of data from the above mentioned study that IMHO is of particular significance. “The mean baseline levels of estradiol and testosterone were 24.5 8.8 pg/ml and 581 165 ng/dl, respectively. Maximal suppression of estradiol (62 14%) was observed 12 h after a single 25-mg dose of exemestane. Estradiol remained suppressed by 58 21% at 24 h and returned to baseline 3–6 d after treatment

    Just want to clear and ensure that I have complete coverage and learn together. Again, thanks in advance Austin. And thank you Jimmy!

    Respect,
    Mick.
    Hey Mick Thanks for the response! I too wish we had more data available and longer duration of administration to be able to more definitively pinpoint dosage - unfortunately we dont. This is far from me saying look this is definitely the way to do this - however given the fact that real experience also seems to prove that traditional dosing recommendations just fall short of doing the job. Combine this with the simple fact that given stanes positive or lack of negative effects due to administration even at high doses and the difficulty in crashing estrogen(in the study even when not administering exogenous test) whats the harm in higher dosing? Well lets find out.

    Again I really wanted to personally document this theory with personal blood work - however when I saw a log elsewhere with blood work conforming my speculations I felt its time to share this. Especially given the dosage protocol being used was exactly what I felt would work best for myself as well. I dont consider this a be all end all on stabe but the start of a ew line of thinking that I am still going to try to substantiate with blood work of my own and it sounds like others here will be doing so as well. The more that do - the more I think that we will find this to be the case for most - if not Ill be the first to amend my line of thinking. However given the real world experiences I see daily it is clear - wherever we end up dosing stane it will be higher than initially thought and recommended. The goal is this be a tarting point or if you will a carry over of your thread taking it a bit further with blood work to substantiate this theory. I hope you in no way take offense to this buddy -it wasnt meant to step on anyones toes. i have, as you know, been researching stane for quite some time now. At any rate these are the types of posts I was in fact hoping for. Lets present all we know - from studies (or sadly study in this case) and real world experience, and iron this out for everyone as best we can.

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    MickeyKnox is offline Banned
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    Excellent response Jimmy!

    I was waiting patiently for your opinion, and it was worth the wait. I will include your link in my thread, Aromasin vs Arimidex , to provoke thought and allow the reader to absorb both perspectives and recommendations in order for them to make an informed decision.

    I look forward to more blood work (long term) from AAS users

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    Bump..

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    So I just saw another log with bloodowrk that supports this position re: stane/ The user is taking 375mgs test and 25 mg stane/day. After a pm I found he is taking it in one dose. His e2 is 74. The stane is obviously working however I think it would be working better if it was split into 2 12.5mg doses. At any rate I think we will see more and more that stane is being under dosed. Another log that definitely supports the position.
    JinNtonic likes this.

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    Goods job Jimmy! Every bit of solid info helps, particularly when its from a current user.

    I have included this link in bold Red in my Aromasin Vs Arimidex thread for very reader to see.

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    Quote Originally Posted by MickeyKnox View Post
    Goods job Jimmy! Every bit of solid info helps, particularly when its from a current user.

    I have included this link in bold Red in my Aromasin Vs Arimidex thread for very reader to see.
    Thanks Mick!

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    Quote Originally Posted by jimmyinkedup View Post
    Thanks Mick!
    Anytime my friend.

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    Jim,


    Fantastic read (great insight by Micky as well). With respect to dietary fats that should be taken with exemestane doses, is there any specific research that supports the optimal amount of fats? Would fish oil or a handful of nuts do?

    Thanks,

    Igi

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    Quote Originally Posted by jimmyinkedup View Post
    So I just saw another log with bloodowrk that supports this position re: stane/ The user is taking 375mgs test and 25 mg stane/day. After a pm I found he is taking it in one dose. His e2 is 74. The stane is obviously working however I think it would be working better if it was split into 2 12.5mg doses. At any rate I think we will see more and more that stane is being under dosed. Another log that definitely supports the position.
    Jimmy-
    So the optimal times to use Aromasin would be 12.5mg at 8am and 12.5mg at 8pm? Just want to make sure I do this correctly in the future. I was going to take the full 25mg dose in the AM, but if you could clarify, I'd appreciate it...

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