Cross Tolerance Amongst AI's

**AnabolicDoc** · 12-14-2012, 10:56 AM

I recently did a brief literature review of aromatase inhibitors as I was looking for a comparison of their relative efficacies. While I didn't find a good answer, I did come across something interesting. It turns out that amongst the non-steroidal 3rd generation AI's, such as anastrozole and letrozole , there is cross tolerance.

This was gathered from information on breast cancer patients, which showed decreased efficacy of 3rd gen AI's after 2 years of use. The same reduced efficacy was noted even if the patient switched from letrozole to anastrozole or vice versa. But if the patient switched from either anastrozole or letrozole to exemestane there was maintained efficacy. (BTW, switching from exemestane to either anastrozole or letrozole demonstrated cross tolerance and reduced efficacy. So this only works when switching to exemestane.) With exemestane there is an incomplete cross tolerance, presumably bc it is the only steroidal 3rd gen AI.

I thought this was significant bc it reasons to me that if you are going to use an AI during a cycle, it should be either letrozole or anastrozole. The AI used for PCT should be exemestane. This way the AI use during the cycle won't reduce the efficacy of the PCT AI. This should yield more effective PCT results.

**AnabolicDoc** · 12-14-2012, 11:00 AM

Sorry, I just realized that I put this in the wrong section. If a moderator can move this to the appropriate section I would appreciate it.
I've been using the phone app, which is convenient but sometimes a little tricky.

**gixxerboy1** · 12-14-2012, 11:14 AM

first i dont use an ai during pct.
2nd those patients are on higher doses and even as you said for years at a time. Taking it for 12 weeks like we do isnt going to be an issue

**AnabolicDoc** · 12-14-2012, 01:48 PM

You may be right about the timing. I would imagine that tolerance is less of an issue with shorter use, which is often the case.

Regarding the dosage, I believe they were taking one tab a day (exemestane 25mg, anastrozole 1mg, and letrozole 2.5mg). So the dosages were similar to those used during a cycle and PCT.

I understand that you don't use an AI in your PCT, so this info has no real importance to you even if cross tolerance is demonstrated with shorter term use. However, many AAS users like an AI in their PCT. In light if this info, some may choose to alternate which AI they use during their cycle and which they use for PCT. That is if they have access to exemestane and anastrozole or letrozole. I don't think there's any downside to reserving exemestane for PCT and using one of the other AI's during a cycle (of course this would only pertain to those that use an AI during PCT).

I thought the phenomenon was interesting, worth sharing, and something that some ppl on this forum would be interested in knowing. I'm sorry you didn't find it helpful. I hope others do and that they share similar bits of info as they encounter them.

**HCL** · 12-14-2012, 03:09 PM

Interesting conclusion.
Some food for thought

Nice finding

**gixxerboy1** · 12-14-2012, 03:15 PM

Originally Posted by AnabolicDoc

You may be right about the timing. I would imagine that tolerance is less of an issue with shorter use, which is often the case.

Regarding the dosage, I believe they were taking one tab a day (exemestane 25mg, anastrozole 1mg, and letrozole 2.5mg). So the dosages were similar to those used during a cycle and PCT.

I understand that you don't use an AI in your PCT, so this info has no real importance to you even if cross tolerance is demonstrated with shorter term use. However, many AAS users like an AI in their PCT. In light if this info, some may choose to alternate which AI they use during their cycle and which they use for PCT. That is if they have access to exemestane and anastrozole or letrozole. I don't think there's any downside to reserving exemestane for PCT and using one of the other AI's during a cycle (of course this would only pertain to those that use an AI during PCT).

I thought the phenomenon was interesting, worth sharing, and something that some ppl on this forum would be interested in knowing. I'm sorry you didn't find it helpful. I hope others do and that they share similar bits of info as they encounter them.

I'm sorry if you think i was giving you a hard time about posting it. Def not my intention. It was an interesting article and def post more stuff if you find it. I was just giving my opinion on how it effect us. nothing against you

**stevelifts** · 12-14-2012, 03:34 PM

It may interest the HRT guys.

**Atomini** · 12-15-2012, 06:47 AM

This is some great info, and although I had no knowledge of any possible tolerance increase to Arimidex or Letrozole , I have ALWAYS suggested that the best AI for use is Aromasin . In the case of increased tolerance, why not then just exclusively use Aromasin for all purposes (both PCT as well as on-cycle) due to no associated tolerance with Aromasin? And there is something to be said for the difference between how we use AIs (and the doses we use them at) and how these AIs and their doses are used in medical application.

**lovbyts** · 12-15-2012, 07:06 AM

Originally Posted by stevelifts

It may interest the HRT guys.

Yes it's interesting but as gig says not so relevant even to hrt guys since we take such a low dose and usually not quite as consistent as you might think.

Still good information to have.

**AnabolicDoc** · 12-15-2012, 09:59 AM

Originally Posted by Atomini

This is some great info, and although I had no knowledge of any possible tolerance increase to Arimidex or Letrozole, I have ALWAYS suggested that the best AI for use is Aromasin. In the case of increased tolerance, why not then just exclusively use Aromasin for all purposes (both PCT as well as on-cycle) due to no associated tolerance with Aromasin? And there is something to be said for the difference between how we use AIs (and the doses we use them at) and how these AIs and their doses are used in medical application.

Thank you. In those same 2 year studies, exemestane (Aromasin ) also showed decreased effectiveness after 2 years of daily use. That's why I suggested using one of the others first and then switching to exemestane for PCT. Or even switching to exemestane after a few years of using either anastrozole or letrozole , for those that don't use an AI in their PCT.

I just wanted to also say that I completely agree with those of you who pointed out the limitations of the application of this data to us (AAS enthusiasts). We don't have estrogen-receptor positive breast cancer, we don't take a full tab each day (I think most ppl are at half a tab eod on cycle when they require an AI), and even for those who of us who use AI's during PCT it is often for only the first week or two.

However, often in medicine regarding the issue of tolerance there is a linear relationship and not an all or nothing phenomenon. I certainly can't prove that is the case here. But I think it may bear some real application to those that are often on cycle and take high doses of Test (or use estrogenic or aromatizing AAS) and consequently take an AI regularly (eod). If such ppl have access to both, then why not reserve exemestane just for PCT, or switch to exemestane every few years (if no AI in PCT)? Also these studies showed development of a tolerance (and cross tolerance) after 2 years of regular use. So it's possible that tolerance can develop after more than 2 years of semi-regular use.

I apologize for being so wordy. It'll take time for that to improve.