AI's and joint pain

[RickB]

Everything I've found online for forever regarding AI's and joint pain basically says that it is most likely due to low E2. I've been using Exemestane for a while now, and have basically been keeping my E2 at 40 and above, and I am having joint pain in a couple of areas. Being that my E2 is much, much higher than it was pre-trt, if Exemestane is the cause of my joint pain, it definitely is not due to my E2 level. Can anyone link any sources that hypothesize AI's causing joint pain through any other action than lowering E2? In fact, even if anyone can give me anecdotal info, I would appreciate it.

(I know that many users will tell me to lower my T dose and drop the AI. However, if I lower my T dose, I am going to be sitting at the same free-T level I was at pre-trt. As madman knows, I took his advice and was tested using Equilibrium Ultrafiltration recently. Even though my free was sky high, as he said it would be, the number that started me on my trt journey a year-and-a-half ago was my direct assay free-T. So even though that number is underestimated, it is still relevant per the symptoms I had. Therefore, even though my true free level is very high, I need it to be that high to alleviate my low-T symptoms...Not sure if any of that made sense, but I just wanted to put it in there before the chorus of "lower your dose" starts. Also, I did try daily dosing. It worked for managing E2 w/o AI and kept my free level good enough. However I grew very tired of daily IM, and I am not fully convinced about subQ, so I prefer to stay on an AI)

 

[FLguy123]

I wonder the same and have a completely unfounded theory that some of the following could contribute to joint pain:

high HCT - maybe less blood/nutrients getting into the joints.
Reaction to carrier oils.
Dehydration - my skin and hair seem quite a bit drier on T therapy, and my urine is darker yellow much more often, I basically drink only water and use electrolyte powder occasionally as well.

 

[RickB]

I wonder the same and have a completely unfounded theory that some of the following could contribute to joint pain:

high HCT - maybe less blood/nutrients getting into the joints.
Reaction to carrier oils.
Dehydration - my skin and hair seem quite a bit drier on T therapy, and my urine is darker yellow much more often, I basically drink only water and use electrolyte powder occasionally as well.

So you have these symptoms without an AI?

 

[FLguy123]

Yes, and they typically present around 3 months after I resume the TRT. When I go off, my joints usually begin to feel better within a few days to a week

 

[TorontoTRT]

See how people only talk about E2 but never total T in relation to it? Yes, your E2 at 40 is low. Low in comparison to your total T. Which means your hormones are not in proper ratio. Stop the AI and see where your body settles. As I mentioned before I run my e2 in the range of 75-100. Why? Because my test is over 1500. Have I ever had high E2 side effects? No. Never. Not even water ration and on top of that lost 30 lbs of fat with high E2. My provider doesn’t even test E2 on blood work anymore. It doesn’t matter. E2 will never go up indefinitely no matter how much testosterone you inject. Just like hematocrit doesn’t go up indefinitely like 60+.

 

[RickB]

See how people only talk about E2 but never total T in relation to it? Yes, your E2 at 40 is low. Low in comparison to your total T. Which means your hormones are not in proper ratio. Stop the AI and see where your body settles. As I mentioned before I run my e2 in the range of 75-100. Why? Because my test is over 1500. Have I ever had high E2 side effects? No. Never. Not even water ration and on top of that lost 30 lbs of fat with high E2. My provider doesn’t even test E2 on blood work anymore. It doesn’t matter. E2 will never go up indefinitely no matter how much testosterone you inject. Just like hematocrit doesn’t go up indefinitely like 60+.

That’s a good point. As much as I’ve heard and read about ratio, I hadnt considered that it could cause low E2 sides.

 

[FunkOdyssey]

Everything I've found online for forever regarding AI's and joint pain basically says that it is most likely due to low E2. I've been using Exemestane for a while now, and have basically been keeping my E2 at 40 and above, and I am having joint pain in a couple of areas. Being that my E2 is much, much higher than it was pre-trt, if Exemestane is the cause of my joint pain, it definitely is not due to my E2 level. Can anyone link any sources that hypothesize AI's causing joint pain through any other action than lowering E2? In fact, even if anyone can give me anecdotal info, I would appreciate it.

(I know that many users will tell me to lower my T dose and drop the AI. However, if I lower my T dose, I am going to be sitting at the same free-T level I was at pre-trt. As madman knows, I took his advice and was tested using Equilibrium Ultrafiltration recently. Even though my free was sky high, as he said it would be, the number that started me on my trt journey a year-and-a-half ago was my direct assay free-T. So even though that number is underestimated, it is still relevant per the symptoms I had. Therefore, even though my true free level is very high, I need it to be that high to alleviate my low-T symptoms...Not sure if any of that made sense, but I just wanted to put it in there before the chorus of "lower your dose" starts. Also, I did try daily dosing. It worked for managing E2 w/o AI and kept my free level good enough. However I grew very tired of daily IM, and I am not fully convinced about subQ, so I prefer to stay on an AI)

At the risk of parroting Bossa and friends, are you aware that serum levels of E2 may not reflect the E2 available to a particular tissue? Each tissue that depends on E2 converts it locally from T with a quantity of aromatase that is specific to the tissue and its requirements. It is then possible that you could take an AI and create a local deficiency of E2 in your joints that is not reflected in the serum E2 measurements.

If you've already proven that daily dosing works well for you except for the inconvenience, could you not return to daily for a limited time and drop the AI to test this hypothesis?

 

[Gman86]

U also have to consider that estrogen is an intracrine hormone. So what we measure in the blood tells us nothing about how much estrogen is in all of our tissues. U could have an E2 in range on bloodwork, and lack estrogen where ur having the pain

 

[Systemlord]

Can anyone link any sources that hypothesize AI's causing joint pain through any other action than lowering E2?

You're screwing with a hormonal pathway which can have unexpected consequences. You may also be dealing with side effects of the medication and not really low E2.

 

[tareload]

Everything I've found online for forever regarding AI's and joint pain basically says that it is most likely due to low E2. I've been using Exemestane for a while now, and have basically been keeping my E2 at 40 and above, and I am having joint pain in a couple of areas. Being that my E2 is much, much higher than it was pre-trt, if Exemestane is the cause of my joint pain, it definitely is not due to my E2 level. Can anyone link any sources that hypothesize AI's causing joint pain through any other action than lowering E2? In fact, even if anyone can give me anecdotal info, I would appreciate it.

(I know that many users will tell me to lower my T dose and drop the AI. However, if I lower my T dose, I am going to be sitting at the same free-T level I was at pre-trt. As madman knows, I took his advice and was tested using Equilibrium Ultrafiltration recently. Even though my free was sky high, as he said it would be, the number that started me on my trt journey a year-and-a-half ago was my direct assay free-T. So even though that number is underestimated, it is still relevant per the symptoms I had. Therefore, even though my true free level is very high, I need it to be that high to alleviate my low-T symptoms...Not sure if any of that made sense, but I just wanted to put it in there before the chorus of "lower your dose" starts. Also, I did try daily dosing. It worked for managing E2 w/o AI and kept my free level good enough. However I grew very tired of daily IM, and I am not fully convinced about subQ, so I prefer to stay on an AI)

What is TRT and What is NOT TRT

https://ascopubs.org/doi/10.1200/JCO.2010.28.5064 Related paper discussing subset of women who experience joint pain on standard AI dosing for cancer treatment. Finally, it is intriguing to speculate that our findings in women receiving AIs who develop MS-AEs may provide insight into the...

forums.t-nation.com

Finally, we knew that interleukin 17 (IL17) and the IL17 receptor A (IL17RA) were both therapeutic targets in patients with rheumatoid arthritis,24 so we determined whether the expression of TCL1A was correlated with the expression of either IL17 or IL17RA in the same 288 lymphoblastoid cell lines. Expression of TCL1A and IL7RA were correlated (r = 0.36; P < 1.9E-10). We then demonstrated in U2OS cells that small interfering RNA knockdown of TCL1A resulted in decreased expression of IL17RA but increased expression of IL17 mRNA (Figs 4A and 4B), while overexpression of TCL1A resulted in increased IL17RA expression and decreased expression of mRNA for the ligand IL17 (Figs 4C and 4D).

 

[tareload]

See two articles in post attached. We are playing in the kiddie pool on the beach of a vast ocean.

TRT: Talk Me Down, Please

Labs? When did you test? Repeats? Include units and reference ranges. Also understand this before you start your adventure: Good self awareness. You will get over it.

forums.t-nation.com

 

[tareload]

https://www.researchsquare.com/article/rs-1315678/latest.pdf

 

[RickB]

At the risk of parroting Bossa and friends, are you aware that serum levels of E2 may not reflect the E2 available to a particular tissue? Each tissue that depends on E2 converts it locally from T with a quantity of aromatase that is specific to the tissue and its requirements. It is then possible that you could take an AI and create a local deficiency of E2 in your joints that is not reflected in the serum E2 measurements.

If you've already proven that daily dosing works well for you except for the inconvenience, could you not return to daily for a limited time and drop the AI to test this hypothesis?

I wasnt aware of that at all. I just might have to go back to daily afterall.

 

[RickB]

You're screwing with a hormonal pathway which can have unexpected consequences. You may also be dealing with side effects of the medication and not really low E2.

Thats exactly what I want to know. It seems theres an overall uncertainty in the medical community whether the drugs themselves are causing certain symptoms regardless of e2 level.

 

[RickB]

https://www.researchsquare.com/article/rs-1315678/latest.pdf

Things definitely going over my head at this point, but for whatever it's worth, I plugged the variants into my 23andMe raw data. Only two of them turned out to have been tested.

For rs9322336 I was T/T for build 37 and build 38
For rs2369049 I was A/A for build 37 and build 38.

So if I'm reading things right, I have the allele likely to mean joint pain for the second variant, but not for the first.