T Nation

Pharmokinetics of Exemestane

Just discovered this article:
http://jcem.endojournals.org/cgi/reprint/88/12/5951?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&title=exemestane&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

Exemestane is a steroidal irreversible aromatase blocker. It says irreversible but in this context I don’t really understand what that would entail (as in more receptors are created vs. take it for 10 days and you are done for life). Interesting read. 25mg ED (half life 8 hours) would be the dosing requirements.

Thanks for posting the link for this article. This is added information to what I already knew since beginning this drug for high estradiol due to TRT three weeks ago.

[quote]Raw Power wrote:
Thanks for posting the link for this article. This is added information to what I already knew since beginning this drug for high estradiol due to TRT three weeks ago.[/quote]

E2=? just curious for a range.

My E2 was 34 pg/mL.

Of course, that was in normal ranges according to LabCorp. (I did my blood test through Life Extension Foundation). The problem was I had all the symptoms of high E even though the numbers were in normal range. An LFE doctor told me that I needed to get that down. I needed to cut the E levels in half is what it came down to. Being on a low dose of TRT (Testim 5g) did increase free and total T, but it also created the higher E and the “parade was rained on”.

Once again, doctors need to treat the symptoms instead of the numbers especially in this case. My doctor insisted that I go on TRT (my total T in the beginning was 135). Now that my E levels have gone up and I had the symptoms my doctor doesn’t want to discuss the issue and when I asked about checking my E levels with a blood test he looked at me like I was crazy and walked out of the examining room. Now I just do my own blood tests and get my medicine elsewhere.

[quote]Raw Power wrote:
My E2 was 34 pg/mL.

Of course, that was in normal ranges according to LabCorp. (I did my blood test through Life Extension Foundation). The problem was I had all the symptoms of high E even though the numbers were in normal range. An LFE doctor told me that I needed to get that down. I needed to cut the E levels in half is what it came down to. Being on a low dose of TRT (Testim 5g) did increase free and total T, but it also created the higher E and the “parade was rained on”.

Once again, doctors need to treat the symptoms instead of the numbers especially in this case. My doctor insisted that I go on TRT (my total T in the beginning was 135). Now that my E levels have gone up and I had the symptoms my doctor doesn’t want to discuss the issue and when I asked about checking my E levels with a blood test he looked at me like I was crazy and walked out of the examining room. Now I just do my own blood tests and get my medicine elsewhere. [/quote]
So you had an LFE doc and the doc that prescribed TRT? And your doc walked out on you? Your doc must be a super douchebag.

I should then be thankful I have a doc that lets me get away with that stuff.

How bad did the excess E make you feel? I am curious, I have not been tested yet but my joints have been hurting more after I started TRT, I ordered an AI and hopefully my doc will get me HCG monday…otherwise there is something else wrong with me, now my elbow and hand hurts as well as my knees.

My doctor keeps brushing me off so I guess I am reaching for an explanation.

[quote]rfish1966 wrote:
How bad did the excess E make you feel? I am curious, I have not been tested yet but my joints have been hurting more after I started TRT, I ordered an AI and hopefully my doc will get me HCG monday…otherwise there is something else wrong with me, now my elbow and hand hurts as well as my knees.

My doctor keeps brushing me off so I guess I am reaching for an explanation.[/quote]

Masturbation is a sign that the T is working and that explains the sore hand and elbow… :wink:

I had a sore elbow that took a few months to resolve. Probably from diving into high resistance low reps.

I would not worry about this. If there is soreness, there is probably a healing process at work as well. Time frame could be 3 to 6 months.

[quote]themonthofjun wrote:
Just discovered this article:
http://jcem.endojournals.org/cgi/reprint/88/12/5951?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&title=exemestane&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

Exemestane is a steroidal irreversible aromatase blocker. It says irreversible but in this context I don’t really understand what that would entail (as in more receptors are created vs. take it for 10 days and you are done for life). Interesting read. 25mg ED (half life 8 hours) would be the dosing requirements.[/quote]

That is a big read. Please note that the authors claim that this drug is an alternative to other AI’s and no claims are made that it is in anyway better for TRT than anastrozole.

This drug and anastrozole are self limiting, in that 50mg is not more effective than 25, and 25 might be overkill as well.

In “lean” young men, there will be less aromatase to deal with in the first place. 25mg as a dose probably comes from work on females who have a lot more E to get rid of when dealing with cancer, and they also have a lot more body fat with aromatase to be treated.

If you can reduce your E to good levels with 1mg/wk of anastrozole, why use exemestane to get to the same target E level when it costs more and you need to take much higher amounts?

The fact that exemestane is a irreversible aromatase blocker means that it the aromatase enzymes that bind to it are permanently out of service. That means a permanent binding. The short 1/2 life of exemestane limits its effectiveness as it takes a while for a drug molecule to randomly find and bind to aromatase molecules. Anastrozole does not permanently bond to aromatase, but competes with E for that binding. You take less of it, but it has a long 1/2 life that makes it very effective. Part of this game will be the number of molecules of exemestane in a dose and absorption efficiency. mg’s of dose is not the whole picture. One also needs to look at the molecular weight of the product. [This explains how 1mg per week of anastrozole can be effective.]

The body is making new aromatase 24/7, so you permanently knock out some while new one’s pop up all the time. After the serum level of exemestane drops, active aromatase still comes to life. With anastrozole, the long 1/2 life of the drug means that there is not a gap in its effect.

The main advantage of anastrozole is a known history of dose/response for males on TRT. The dose probably needs to be scaled somewhat to one’s body weight, E levels and %BF. But individual variability in response may make such first dose calculations a waste of time.

Both drugs are self limiting as there are a finite number of FREE aromatase molecules for the drug molecules to ‘find’. With the first dose there is a given effect. When the dose is increased beyond that, there are fewer FREE aromatase molecules for the drug molecules to randomly find the fewer remaining FREE aromatase molecules. For both drugs, doubling the dose does very little. Think of the 80:20 rule.

This self limiting effect can avoid taking E levels to zero which risks CV health and libido. Femara is an AI that can take E to undetectable levels which is dangerous. Some will go extremely low on E with 10% of a dose. So there is more risk. The only way for a male to use femara in a TRT context would involve a lot of blood work that would erase any cost savings implied by the cost and dose of femara. Femara should be reserved for dealing with gyno in short term dosing, mostly a body builder gear situation.

Compounding the above unknowns, we can expect that the body will somehow react against such interventions. I would be surprised if the body is not increasing aromatase in response to AI drugs. This suggests that short term blood work response may not the complete picture. And if one looses body fat, that can increase the effective dose as well by reducing the number of aromatase target molecules in the body.

[quote]themonthofjun wrote:
So you had an LFE doc and the doc that prescribed TRT? And your doc walked out on you? Your doc must be a super douchebag.

I should then be thankful I have a doc that lets me get away with that stuff.

[/quote]
I’ll give you the background as briefly as I can:

I had gone to my first visit with my new doctor last Fall with an unrelated upper back injury. He took one look at me and decided in his mind that I must have been on steroids because I had size. This was not true and I had always been a drug free powerlifter. Anyway, like most docs with athletes, he wanted to go on a “fishing expedition” and ordered a bunch of blood tests.

I did them and reported back in a couple of weeks to be told that my T level was 135 and I was hypogonadal and that I needed to be on TRT immediately. At first I refused because I knew if I did this I would not be allowed to compete in drug free powerlifting anymore. However, he convinced me for health reasons and prescribed Testim (transdermal gel) and then gave me a T injection before I left the office.

Since then he has basically abandoned me with TRT. When I try to talk to him about it or ask questions he just blows it off. He wouldn’t listen to my concerns about high E, wouldn’t do anymore blood work and just told me, “Don’t worry about it” and walks out of the room while I am talking to him as usual. My doctor opened “Pandora’s box” and now doesn’t want to deal with it. I have asked several times to be referred to an endo and he refuses saying that it’s not necessary. Needless to say, I’m angry because now I cannot compete anymore but what makes it worse is that now I have issues with the TRT he prescribed and he doesn’t want to deal with it.

I’m in a HMO type program and I have been assigned to this doctor for the remaining of the year. I will get another doctor next year. The only choices I have now are either to treat myself for my problem or go to another doctor and pay out of pocket for all my expenses.

With LFE you have a doctor’s order allowing the blood test to be conducted. I had called up Quest to see if I could just come in and pay to have a blood test done and was promptly told, “No!”. Once I got my E blood test results an LFE doctor consulted with me on the phone about it and could only offer over-the-counter supplements to lower the E. I asked if I needed Arimidex and was told, “Yes, but I can’t send that to you”.

An LFE doctor did not prescribe to me TRT or Exemestane. I have been on TRT through my regular doc and I had to get the exemestane from an underground lab in the form of research chemicals.

I know that I need HCG injections and would like to get away from transdermal gels, but I know that my doctor isn’t going to listen to me. As I said earlier, when I asked about high E and doing blood work he thought I had lost my mind, wouldn’t listen and walked out on me so I know that he won’t listen to any of these other suggestions. I guess I’m kind of stuck right now.

I am envious of the men on this forum who have docs that listen to their patients, their concerns and requests and are willing to treat symptoms. Yes, be thankful that you have a good doc and take advantage of all that is offered to you.

Ha, maybe thats a good medical reason to enlist my wife…it is afterall to help with my joints : ) I guess I could just use the right hand but that one is already hairy.

[quote]KSman wrote:
Masturbation is a sign that the T is working and that explains the sore hand and elbow… :wink:

I had a sore elbow that took a few months to resolve. Probably from diving into high resistance low reps.

I would not worry about this. If there is soreness, there is probably a healing process at work as well. Time frame could be 3 to 6 months.[/quote]