[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.
