Author Topic: Are We Interpreting Testosterone Levels Wrongly?  (Read 146 times)

Sham

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Are We Interpreting Testosterone Levels Wrongly?
« on: January 23, 2018, 10:25:08 AM »
I wanted to share something that I have believed for some time, but don’t ever hear anyone talking about. Maybe I am not correct in thinking this, or perhaps it is just not common knowledge. Please let me know what you think.

This applies to injected testosterone, not so much for gel, and particularly for younger men.

A testosterone level of, for example, 12 nmol/l naturally is not equal to a level of 12 nmol/l when on TRT.

When measured before TRT is started, the 12 nmol/l is usually a peak level for that day, being measured in the morning. It will drop down to perhaps 5-8 nmol/l in the afternoon / evening which follows the natural diurnal variation in younger men. Whereas when on TRT, that 12 nmol/l will be pretty constant throughout the day, meaning your body is under the influence of a much higher level of testosterone. Since testosterone level is usually measured at trough when on TRT, the level before this will actually be considerably higher. I could guesstimate that a level of 12nmol/l on TRT is ‘equivalent’ to a natural level of maybe 20 nmol/l.

So what I’m saying is, if you start TRT and your testosterone level does not show much improvement, that may not actually be the case.

I would suggest that anyone on injectable TRT with a testosterone level of above, say 18-20 nmol/l (?), is actually receiving supraphysiological doses of testosterone when considering the day as a whole.

This may be why many men on TRT also require an aromatase inhibitor and sometimes have problems with haematocrit - their testosterone level looks normal according to the numbers, but actually their body is receiving a much higher amount of testosterone than someone with the ‘same’ natural level.

This difference would be reduced with older men whose natural testosterone level tends to be more stable throughout the day.

Men on TRT would tend to have lower SHBG than those naturally producing testosterone, to that would increase free testosterone yet further.

Please let me know your thoughts on this. Am I missing something here?

Olly13

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Re: Are We Interpreting Testosterone Levels Wrongly?
« Reply #1 on: January 23, 2018, 03:46:00 PM »
I wanted to share something that I have believed for some time, but don’t ever hear anyone talking about. Maybe I am not correct in thinking this, or perhaps it is just not common knowledge. Please let me know what you think.

This applies to injected testosterone, not so much for gel, and particularly for younger men.

A testosterone level of, for example, 12 nmol/l naturally is not equal to a level of 12 nmol/l when on TRT.

When measured before TRT is started, the 12 nmol/l is usually a peak level for that day, being measured in the morning. It will drop down to perhaps 5-8 nmol/l in the afternoon / evening which follows the natural diurnal variation in younger men. Whereas when on TRT, that 12 nmol/l will be pretty constant throughout the day, meaning your body is under the influence of a much higher level of testosterone. Since testosterone level is usually measured at trough when on TRT, the level before this will actually be considerably higher. I could guesstimate that a level of 12nmol/l on TRT is ‘equivalent’ to a natural level of maybe 20 nmol/l.

So what I’m saying is, if you start TRT and your testosterone level does not show much improvement, that may not actually be the case.

I would suggest that anyone on injectable TRT with a testosterone level of above, say 18-20 nmol/l (?), is actually receiving supraphysiological doses of testosterone when considering the day as a whole.

This may be why many men on TRT also require an aromatase inhibitor and sometimes have problems with haematocrit - their testosterone level looks normal according to the numbers, but actually their body is receiving a much higher amount of testosterone than someone with the ‘same’ natural level.

This difference would be reduced with older men whose natural testosterone level tends to be more stable throughout the day.

Men on TRT would tend to have lower SHBG than those naturally producing testosterone, to that would increase free testosterone yet further.

Please let me know your thoughts on this. Am I missing something here?

Good point raised.

I'm finding my self agreeing and slightly disagreeing simultaneously. I agree that obviously there is no change throughout the day when injecting exogenous testosterone, compared to endogenous production, however that doesn't mean 12nmol/L suddenly = 20 nmol/L.

The point is if a hypogonadal man has a morning peak of 12 nmol/L and an evening reading of 9 nmol/L he is still hypogonadal. Whereas if a healthy male had a level of 22 in the morning, it's gives room for it to drop to say 18 nmol/L and still feel perfectly fine, you have to remember it's not like testosterone production magically falls of a cliff past mid day, albeit its lower but there will still be enough.

I don't believe older males have much more stable testosterone levels throughout the day compared to younger men, unless you have a study (and a decent one at that) I'm not totally convinced, although the higher SHBG in older men will assist "evening it out" somewhat...

Yes SHBG does decrease in TRT users, which is good for those with it too high, however low SHBG is also bad, and adding TRT doesn't help the issue, there is a very recent study showing SHBG is actually rather beneficial, as we already know it acts as a "Buffer" to a degree.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/

It's a rather complicated article, so if I've got it Wrong in some way then please correct me.

I also don't see how 18 nmol/L trough can translate to supraphysiological levels unless we're talking about nebido, in which case "maybe". You have to account for the way the testosterone is spaced out, if the dose is low and the intervals short then you'll get less peak and trough (think 0.5ml Sustanon for example), so obviously the trough level is going to be higher than someone on a comparison dose nebido with its massive dose and massive trough to go with it.

I'm going to use myself as an example, my Testosterone is about 19.8-22.8 at trough, if my testosterone was lower so would my oestradiol, my oestradiol has frequently been suspect of being too low, so you can't say that everyone who is walking around with testosterone is the low 20's has higher e2.

Hematocrit is a puzzle and to a point I agree, however when you see guys on Clomid with testosterone up in the higher 20's low 30's they all have normal hematocrits, I also doubt that there testosterone will be much different later in the day due to the clomid, so why would they have a normal hematocrit and those on TRT have higher? Honesty I've been looking for the answer to this since it ever crossed my mind, I can only assume its due to TRT Being exogenous, compared to endogenous, but again why is the question.

I know it sounds like I'm disagreeing, but I'm not, what I'm trying to say is "it depends" and to be totally honest they are questions no one really knows the answers too, at least not yet anyway, theory's on the other hand there are plenty of those. :)

Sham

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Re: Are We Interpreting Testosterone Levels Wrongly?
« Reply #2 on: January 23, 2018, 04:52:08 PM »
I'm finding my self agreeing and slightly disagreeing simultaneously. I agree that obviously there is no change throughout the day when injecting exogenous testosterone, compared to endogenous production, however that doesn't mean 12nmol/L suddenly = 20 nmol/L.

The point is if a hypogonadal man has a morning peak of 12 nmol/L and an evening reading of 9 nmol/L he is still hypogonadal. Whereas if a healthy male had a level of 22 in the morning, it's gives room for it to drop to say 18 nmol/L and still feel perfectly fine, you have to remember it's not like testosterone production magically falls of a cliff past mid day, albeit its lower but there will still be enough.

My figures were just plucked out of the air to give an idea of what I was talking about, I don't necessarily mean 12 nmol/l = 20 nmol/l.

I think we might need to rethink this - a natural level of 12 nmol/l is clearly hypogonadal, but is a TRT level of 12 nmol/l? I'm not so sure. Does the level dictate if someone is hypogonadal, or does the overall exposure to testosterone throughout the day dictate it? Because there will be a LOT more testosterone (when considering the day as a whole) in someone at 12 nmol/l on TRT than someone natural - I could say as much as double having looked at various plots. Or is it a threshold below which you experience low t symptoms, so even if you were at 12 nmol/l 24 hours of the day, you would still be low because you don't reach a hypothetical 'magic' 13 nmol/l. This is dabateable I think.

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I don't believe older males have much more stable testosterone levels throughout the day compared to younger men, unless you have a study (and a decent one at that) I'm not totally convinced, although the higher SHBG in older men will assist "evening it out" somewhat...

The fact that older men have less diurnal variation is well known. It starts at puberty when LH is first being produced - initially it is released only at night, with nothing during the day, then gradually as puberty progresses it starts to be released during the day as well. The initial peak which started during puberty then reduces as the man gets older, and eventually the release pretty much evens out. I have seen plenty of studies about this and here is one example:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681273/

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Yes SHBG does decrease in TRT users, which is good for those with it too high, however low SHBG is also bad, and adding TRT doesn't help the issue, there is a very recent study showing SHBG is actually rather beneficial, as we already know it acts as a "Buffer" to a degree.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/

It's a rather complicated article, so if I've got it Wrong in some way then please correct me.

SHBG is very important and this is only starting to be understood. I has it's own receptor, and the testosterone bound to the SHBG can still exert some effect when the T+SHBG binds to the SHBG receptor, although it is not yet known exactly what effect this has. What is important is to have SHBG mid-range, either extreme is not good.

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I also don't see how 18 nmol/L trough can translate to supraphysiological levels unless we're talking about nebido, in which case "maybe". You have to account for the way the testosterone is spaced out, if the dose is low and the intervals short then you'll get less peak and trough (think 0.5ml Sustanon for example), so obviously the trough level is going to be higher than someone on a comparison dose nebido with its massive dose and massive trough to go with it.

I'm going to use myself as an example, my Testosterone is about 19.8-22.8 at trough, if my testosterone was lower so would my oestradiol, my oestradiol has frequently been suspect of being too low, so you can't say that everyone who is walking around with testosterone is the low 20's has higher e2.

It depends on how you define supraphysiological. If you think of it as being above a certain level, then no, you won't be supraphysiological. But if you think outside the box and consider the 'area under the curve' rather than the headline level, then it just might be. Would someone with a constant level of 22 nmol/l be under the infuence of a greater amount of testosterone throughout the day than someone who only peaks at 22 nmol/l - certainly they would be - would this make them supraphysiological? Maybe not under the conventional definition, but it is something to think about.

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Hematocrit is a puzzle and to a point I agree, however when you see guys on Clomid with testosterone up in the higher 20's low 30's they all have normal hematocrits, I also doubt that there testosterone will be much different later in the day due to the clomid, so why would they have a normal hematocrit and those on TRT have higher? Honesty I've been looking for the answer to this since it ever crossed my mind, I can only assume its due to TRT Being exogenous, compared to endogenous, but again why is the question.

Clomid just amplifies the normal production of LH, it still rises in the morning and drops later in the day - so it will be a peak level of e.g. 30 nmol/l, not a constant 30 throughout the day. So it will be nothing like someone with a level of 30 nmol/l on TRT. I believe the natural drop throughout the day is often underestimated.
« Last Edit: January 23, 2018, 04:56:31 PM by Sham »

Sham

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Re: Are We Interpreting Testosterone Levels Wrongly?
« Reply #3 on: January 23, 2018, 06:05:09 PM »
Another way of thinking about it is like this: Imagine you’re on TRT and at 08:00 your level is 25 nmol/l  - you are not supraphysiological as you are within range for that particular time of the day. Later in the day when your body would normally be demanding a lower level of testosterone, you are still at 25 nmol/l. Now the upper limit of the normal range is based on the peak level for the day, not the maximimum level at 16:00 for example, so perhaps it is not correct to say that you are still in range. You could see it like being supraphysiological in the afternoon but not the morning. So someone on TRT could be supraphysiological for most of the day, except for a brief period in the morning when their testosterone matches what their body would normally want.

Olly13

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Re: Are We Interpreting Testosterone Levels Wrongly?
« Reply #4 on: January 23, 2018, 09:10:52 PM »
Interesting study regarding the whole age and Testosterone decline though the day thing, I stand corrected! ;) I'm betting it'll be the higher levels of shbg.

I do agree which it's worth being mindful over the mean levels of testosterone over a period of time, for both TRT and guys just getting endogenous levels tested. This is why I always ask if a blood test is done in the morning upon waking when people post on here.

What you do have to remember is that no therapy is perfect, you could argue gels spike to a supraphysiological range 2-3 hours after application, it's all a trade off. In the ideal world we'd all inject a micro dose of propionate and HCG every Morning, but even then there is going to be a caveat somewhere. I'd just enjoy the fact TRT users don't have an evening Trough on injectables, it's hardly a bad thing is it? Funnily enough from an anecdotal point of view I spent half my life having an evening "downer" every day like clockwork, since TRT it's gone, so yeah from a hypogonadal perspective the evening trough of endogenous testosterone isn't something to laugh at.

Regarding clomid I'd still hypothesise that you'll get less variation throughout the day, simply because you are taking a drug to trick the pituitary into pumping out LH and FSH, yes there will still be a drop I'm not denying that, but likely a smaller one, and once again too many variables to say for sure either way imo.

:)