TRT 3 years in - Labs coming back higher on same old dosing

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I’ve been on TRT for 3 years now. Played the game with a reluctant and partially educated dr to end up taking 120mg a week in split doses. I worked up to this dose after 100mg every 2 weeks, 80mg, and 100mg a week. 120mg a week ended up being a good max dosage for me as I need no AI and push upper boundaries in all T labs and keep my E2 in check. My dr. Has me do labs 2x a year and for the last year or so I’ve been seeing my T values go up. When I was working my way up to my max dose 80mg had always put my total T around 520, 100mg put me at 720mg and 120 put me around 940 range for these 250-1100. Within the last year I’ve been seeing these values go up on the same dosages. Just this week i did labs and my dr. Only wanted to test total T for some reason. Roughly 100mg a week had me at 1042 TT 300-890. I should have mentioned all previous tests were by the lc ms/ms method. Range 250-1100. I’m confused what could be changing in my body that these values are increasing on the same amount of T. I do supplement with a multivitamin, grapeseed, turmeric, co q10, DIM with calcium d-glucate, rez-v, l-Theanine, 7-keto and ZMA at night. I’m wondering if the zinc supplemention through the multi and ZMA could be causing the increase in T values. Thought one of the prominent TRT Dr’s used zinc on low with low doses of TRT for this reason. If anyone has any input, I’d like to hear it. Thanks in advance.

[Youthful55guy]

First thought is that I too have observed some what variable responses to TRT with a stable dose. I suspect that it has to do with how much SHBG you are producing. I've done uncountable SHBG labs and I find it to be somewhat variable. Most guys produce more SHBG as we age and this is part of the reason why our Free T decreases with age. The other reason is that we just simply make less T as we age, but by taking production out of the equation by artificially injecting T, you are left with SHBG variability as the source of variability in T levels.

SHBG binds to T and protects it from liver metabolism. This increases T as measure with the Total T lab. From the surface, this seems like a good idea, but in application, SHBG bound T cannot pass through the blood-brain barrier (where you need it to feel like a guy) and it also drives Free T down. It's Free T that's the active form of the hormone. Since SHBG increases with age, it might explain why your Total T labs are drifting upward.

Bottom line is that you should not be adjusting your T dose based on Total T labs. You should be basing the dose on Free T. You want to keep Free T in the upper 75th percentile of a 30-40 year old guy and that's about 21-22 pg/mL. I wouldn't push it any further than 26 pg/mL (100% top end of the range for a 20-30 year old guy.

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First thought is that I too have observed some what variable responses to TRT with a stable dose. I suspect that it has to do with how much SHBG you are producing. I've done uncountable SHBG labs and I find it to be somewhat variable. Most guys produce more SHBG as we age and this is part of the reason why our Free T decreases with age. The other reason is that we just simply make less T as we age, but by taking production out of the equation by artificially injecting T, you are left with SHBG variability as the source of variability in T levels.

SHBG binds to T and protects it from liver metabolism. This increases T as measure with the Total T lab. From the surface, this seems like a good idea, but in application, SHBG bound T cannot pass through the blood-brain barrier (where you need it to feel like a guy) and it also drives Free T down. It's Free T that's the active form of the hormone. Since SHBG increases with age, it might explain why your Total T labs are drifting upward.

Bottom line is that you should not be adjusting your T dose based on Total T labs. You should be basing the dose on Free T. You want to keep Free T in the upper 75th percentile of a 30-40 year old guy and that's about 21-22 pg/mL. I wouldn't push it any further than 26 pg/mL (100% top end of the range for a 20-30 year old guy.

Thanks for the reply youthful55guy. I’m 46 and actually my SHBG generally runs relatively low, from high teens to low 20’s. I suspect my free t would have been out of the range too. Not by a lot but out none the less. I really feel like it’s a timing issue along with dr’s choice of test. I mean the unit of volume is the same as an lc ms/ms T test but the range is so much lower. So if I would have taken the lc ms/ms test would I have been in the range? or can these two tests and results not be compared this way? Other thing is I feel great, zero sides and other labs were perfect. Also I think this value is likely my peak as I inject every 3.5 days. I’ve done my own labs from 24hrs, 48hrs, 58hrs, etc after inject to try to get a good picture of how my body responds.

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First thought is that I too have observed some what variable responses to TRT with a stable dose. I suspect that it has to do with how much SHBG you are producing. I've done uncountable SHBG labs and I find it to be somewhat variable. Most guys produce more SHBG as we age and this is part of the reason why our Free T decreases with age. The other reason is that we just simply make less T as we age, but by taking production out of the equation by artificially injecting T, you are left with SHBG variability as the source of variability in T levels.

SHBG binds to T and protects it from liver metabolism. This increases T as measure with the Total T lab. From the surface, this seems like a good idea, but in application, SHBG bound T cannot pass through the blood-brain barrier (where you need it to feel like a guy) and it also drives Free T down. It's Free T that's the active form of the hormone. Since SHBG increases with age, it might explain why your Total T labs are drifting upward.

Bottom line is that you should not be adjusting your T dose based on Total T labs. You should be basing the dose on Free T. You want to keep Free T in the upper 75th percentile of a 30-40 year old guy and that's about 21-22 pg/mL. I wouldn't push it any further than 26 pg/mL (100% top end of the range for a 20-30 year old guy.

Thanks for the reply youthful55guy. I’m normally a low SHBG guy. Pretty consistently in high teens low 20’s since I started but because I just got an immunoassay total T lab I don’t know the whole picture with this set of labs. That’s another part of my dr’s decision making I don’t understand. It may have been a good thing because if I’m still running on the low end there I’d imagine my free T would have been out of the range as well. It’s been slightly out before when I was at 1000 total but it wasn’t a big deal like this most recent lab was. The other part of this is I feel great, am having zero sides and the rest of my labs are perfect.

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Well to bring this thread full circle I received an unexpected phone call from my Dr.’s office this past monday and They called to tell me my testosterone labs came back normal. So I logged on to the portal and it appears my Dr. Ran two sets of labs for T. An immunoassay as well as an LC MS/MS comprehensive for T. I think he was only gonna run the immunoassay until the nurse came in to draw blood and I started asking her about which T test he ordered so she drew a plain red top just incase. This result was exactly what I would have expected.

total t 971 250-1100
Free T 144 46-224
Bioavailable 316 110-575
SHBG 34 10-50
Albumin 4.8 3.6-5.1

seems the consensus is that the lc ms/ms is the standard for testing T and the immunoassay can overestimate T. If anyone has any influence with their Dr or a say in their treatment, then I would never let them use the immunoassay method for a T lab. Of course most know that doesn’t tell the whole story anyway. So in the end my dr. Agreed to allow me to stay on my previous dose of 120mg a week rather than cut me back to 60mg every 5 days which only amounts to 84mg a week.
My next puzzle is the fact that my SHBG went up from what has always been 15-22 to 34. Don’t know if this is good bad or otherwise but I know my free T at peak would be pretty high even at 100-120mg a week when it was lower. Now it’s just a little above the middle which theoretically could call for a dose increase if anything. I was briefly looking to see what could have changed that and it appears through one paper I found that rezveratrol can increase SHBG. Guess that results in smoother more consistent Free T levels. I would think that would be a desired effect.

[Youthful55guy]

Well to bring this thread full circle I received an unexpected phone call from my Dr.’s office this past monday and They called to tell me my testosterone labs came back normal. So I logged on to the portal and it appears my Dr. Ran two sets of labs for T. An immunoassay as well as an LC MS/MS comprehensive for T. I think he was only gonna run the immunoassay until the nurse came in to draw blood and I started asking her about which T test he ordered so she drew a plain red top just incase. This result was exactly what I would have expected.

total t 971 250-1100
Free T 144 46-224
Bioavailable 316 110-575
SHBG 34 10-50
Albumin 4.8 3.6-5.1

seems the consensus is that the lc ms/ms is the standard for testing T and the immunoassay can overestimate T. If anyone has any influence with their Dr or a say in their treatment, then I would never let them use the immunoassay method for a T lab. Of course most know that doesn’t tell the whole story anyway. So in the end my dr. Agreed to allow me to stay on my previous dose of 120mg a week rather than cut me back to 60mg every 5 days which only amounts to 84mg a week.
My next puzzle is the fact that my SHBG went up from what has always been 15-22 to 34. Don’t know if this is good bad or otherwise but I know my free T at peak would be pretty high even at 100-120mg a week when it was lower. Now it’s just a little above the middle which theoretically could call for a dose increase if anything. I was briefly looking to see what could have changed that and it appears through one paper I found that rezveratrol can increase SHBG. Guess that results in smoother more consistent Free T levels. I would think that would be a desired effect.

A couple of thoughts.

1) The LC/MS/MS assay is technically a better assay for T, but it is also more expensive. If Insurance is footing the bill, that's OK. But if you're footing the bill (as I often do with extra labs) then I go with the standard immunoassay. Guys who are on higher doses of T (e.g., bodybuilders) and expect Total T to be higher than 1500 ng/dL and they want to know the exact amount over 1500, then they should go with the LC/MS/MS test method. If you expect results <1500, then the immunoassay is a good less expensive choice.

2) The LC/MS/MS chatter gets messy because for E2 it is by far the better choice. There is much more cross-reactivity with the E2 immunoassay than there is with the T assay. Personally, I would never use the E2 immunoassay even if they call it "sensitive".

3) Bioavailable T is also a good choice. Not sure what test method is used, but my doc runs it in addition to Total and Free and it always seems to parallel the Free T quite well.

4) My SHBG bounces around a little too. It's always high, but just how high seems to vary a bit. Not sure exactly what causes this, but I've seen it too.

Overall, I think your protocol is sound, Cutting back just a little and increasing the frequency might smooth things out, but then again, I always tell my doc when she suggests changes to my protocol that I don't want to try to fix what isn't broken!

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A couple of thoughts.

1) The LC/MS/MS assay is technically a better assay for T, but it is also more expensive. If Insurance is footing the bill, that's OK. But if you're footing the bill (as I often do with extra labs) then I go with the standard immunoassay. Guys who are on higher doses of T (e.g., bodybuilders) and expect Total T to be higher than 1500 ng/dL and they want to know the exact amount over 1500, then they should go with the LC/MS/MS test method. If you expect results <1500, then the immunoassay is a good less expensive choice.

2) The LC/MS/MS chatter gets messy because for E2 it is by far the better choice. There is much more cross-reactivity with the E2 immunoassay than there is with the T assay. Personally, I would never use the E2 immunoassay even if they call it "sensitive".

3) Bioavailable T is also a good choice. Not sure what test method is used, but my doc runs it in addition to Total and Free and it always seems to parallel the Free T quite well.

4) My SHBG bounces around a little too. It's always high, but just how high seems to vary a bit. Not sure exactly what causes this, but I've seen it too.

Overall, I think your protocol is sound, Cutting back just a little and increasing the frequency might smooth things out, but then again, I always tell my doc when she suggests changes to my protocol that I don't want to try to fix what isn't broken!

1. That’s exactly what I do and When I’m with my dr. Insurance is paying so no worries. When I run private labs I don’t go all out. I’ve done some light research and let the endocrine society they only recommend lc ms/ms. Said that immunoassay can over estimate. In my case appears to have by close to 100 points which doesn’t matter to me as much as it matters to my dr., so I guess it does matter to me bc he wanted to dial my dose back almost 40mg a week bc of one elevated value.

4. My SHBG has always run lower, 15-21 and that’s where it was when I tested in June. In August I began supplementing with Rezveratrol daily then I’m at 34. Ive made no other changes really to account for that. I’ve found one study that says Rez v increases SHBG and how. Guess this can be good for guys that want to increase theirs so they have more stable T / free T levels while on therapy.

[Youthful55guy]

1. That’s exactly what I do and When I’m with my dr. Insurance is paying so no worries. When I run private labs I don’t go all out. I’ve done some light research and let the endocrine society they only recommend lc ms/ms. Said that immunoassay can over estimate. In my case appears to have by close to 100 points which doesn’t matter to me as much as it matters to my dr., so I guess it does matter to me bc he wanted to dial my dose back almost 40mg a week bc of one elevated value.

I'd be interested in any links you might have to this information about the T immunoassay measuring high. I'd like to read it and tuck it away in my reference file. I may need to change my recommendation and my own testing. Then again, I have so many labs with the immunoassay technique, it might confuse interpretation of past results if I switched. At the very least, I may be able to convince my doc to add the LC/MS/MS lab in as part of my annual check up labs (insurance paid) if I can convince her that the lab is more accurate and I have a reference to back me up.

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I'd be interested in any links you might have to this information about the T immunoassay measuring high. I'd like to read it and tuck it away in my reference file. I may need to change my recommendation and my own testing. Then again, I have so many labs with the immunoassay technique, it might confuse interpretation of past results if I switched. At the very least, I may be able to convince my doc to add the LC/MS/MS lab in as part of my annual check up labs (insurance paid) if I can convince her that the lab is more accurate and I have a reference to back me up.

FWIW

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