T Nation

Blood Test Done, Low Free T and E2


#1

Hello to everyone. I received the results of my bloodwork this afternoon. I'm 24 years old (male).

TSH 2.23 mU/L (0.27-4.20)
Prolactin 243 mU/L (86-324)
LH 5.7 U/L (1.7-8.6)
FSH 3.0 U/L (1.5-12.4)
E2 less than 92 pmol/L (99-192)
Testosterone 15.13 nmol/L (7.57-31.40)
Free test. 7.71 pg/mL (8.80-27.00)

E2 and free testosterone are below the lower limit. And is total testosterone ok for a 24 years old guy?

In the last two years i've had some difficulties in maintaining erections, no morning woods, sometimes loss of libido. In the same period i've experimented a lot of hot flashes, and intolerance to high temperatures.

May it be related to these ormonal levels?

Some more informations about me: 24 yo as i've said before, height 175 cm, weight 73 kg, i'm not taking any RX or OTC drugs, except a weak antihistamine (cetirizine HCL). I don't drink, I don't smoke, i train 3 times a week at the gym for 90 minutes. I haven't done any low calorie diet.


#2

The total testosterone value doesn’t determine the biological effect of the testosterone: only the free (measured, or calculated from total correct for SHBG) does.

Total testosterone being in the normal range is a consequence simply of having a lot of SHBG. It is the equivalent of this: far more testosterone is dissolved in fat in the body than is in the blood. Suppose we had a “real” total testosterone figure which included everything dissolved in fat, no more active than when bound to SHBG. A fat guy could have a huge “real total testosterone” figure but it would mean nothing. Free T in the blood is what has meaning.

Your results suggest reduced testicular function but also not optimal hypothalamic function either, as with those free T and estradiol levels LH and FSH should be higher. However, a single test isn’t at all conclusive there, as release is pulsatile.

Your TSH indicates mild hypothyroidism but likely not bad enough to be an explanation. For this, using iodized salt on your food is the simplest answer, or if declining to do that, then kelp tablets at for example 300 mcg/day.

I would do a ferritin test to see if your body has built up excess iron: this is a possible cause.


#3

[quote]Bill Roberts wrote:
The total testosterone value doesn’t determine the biological effect of the testosterone: only the free (measured, or calculated from total correct for SHBG) does.

Total testosterone being in the normal range is a consequence simply of having a lot of SHBG. It is the equivalent of this: far more testosterone is dissolved in fat in the body than is in the blood. Suppose we had a “real” total testosterone figure which included everything dissolved in fat, no more active than when bound to SHBG. A fat guy could have a huge “real total testosterone” figure but it would mean nothing. Free T in the blood is what

[/quote]
I know that free testosterone is important and in fact it was measured. It is the last valute of the list, it is out of the normal range (too low).


#4

Yes, I saw it, and my response was based on it. The quoted block of text was from your asking whether total testosterone was OK.


#5

Your TSH should be closer to 1.0

Please read the ‘advice for new guys’ sticky and note the first paragraph.
Also check your body temperatures - see ‘thyroid basics’ sticky
Low thyroid function can affect T levels and generally slow down all cellular activity.
If you gave not been getting enough iodized salt, that can easily be corrected. You should be using iodized salt if available. If not, simply starting iodized salt is not enough to correct the problem.

E2 levels need to balance testosterone levels. For guys on TRT with high range T levels, E2=22pg/ml is a good target. That is 81pmol/L, so your lab ranges seem to be not useful. Perhaps there is a different lab that you can order that has better sensitivity. Discuss with your doctor.

Have your testes physically examined, there can be problems there.

Also see the sticky about things that damage your hormones.

We see a lot of guys here with similar issues who are as young as you.

I have suggested that you look at three stickies, look for a better E2 lab, have testes examines, report body temperatures and look into iodine issues.

Where are you located?


#6

The temperature was 97.8 this morning and 98.15 in the middle of this afternoon. I’ll keep on measuring.

I’m seeing an andrologist this afternoon and I’ll be contacted by an endocrinologist who I know to be a good one. A friend of mine showed him my blood work and he told me that he’s gonna phone me because he has to talk with me so I guess I didn’t not like my values…

But better an hormonal than a mental problem, I think… my GP always minimezed the problem saying that it is all in my head and I had to insist to have the prescription for the blood work (in my country the national health system refunds the medical exams, I don’t know how it is in the US). When i asked him for the test he didn’t remember the funtion of LH and he had to search it on his laptop…

I didn’t agree with him because my problems are more evident when I’m alone while my erection are better when I’m with a girl… Add to this some other problems, like the fact that I’ve lost 14 lbs in the last 3 months…

Anyway I’m located in the northern Italy, near Milan.


#7

Updates.

I measured my temperature in these days and it was about 98 °F in every measurement.

I went to the andrologist/urologist today. He said that Free Testosterone is not important because TT is what really matters and he also told me that i don’t have to worry because my prolactin is in the high part of the range and prolactin is the hormon of sexual desire.

I’ve always heard that FT is what is effectively important and I actually thought that high prolactin is not good for the sex drive.

What to do? Trust him or change doctor?


#8

Change doctor.

Perhaps where he is getting his prolactin statement from is that abnormally low prolactin can impair libido, and so you do not have that impairment.

However, having the prolactin level that you does not guarantee you everything is fine for libido, particularly when you’ve told him it’s not.

Your prolactin level is one that could allow good libido if all else were good. But your free T is too low, and he is wrong to ignore it.

If he is like most American doctors working at this same level, then if after years of practice and medical school he’s still at this level of ignorance, then he cannot be educated now either. So the only good option is a new doctor.


#9

I agree. He just did an urological visit, he only checked the prostate. He did nothing about my erection problem, he just looked at my blood work and said that my values are good because i have high prolactin, and that i shouldn’t worry about FT because it isn’t an important value.

I knew it, that he would say that i’m ok because TT in 400’s is in the range.

But i know another andrologist who put a friend of mine on TRT, and he had a higher test than mine…


#10

Free T is not an important value. Free-T tests are very unreliable, and it is “bioavailable T” (also called “free and loosely bound T”) that is biologically important. Free T is only a tiny fraction of that. Bioavailable T can be calculated from total T and SHBG (and, technically, albumin).


#11

I do not believe you will be able to find a single pharmacology article, published in a peer reviewed journal anywhere in the world at any time, or any pharmacology text that ever uses “bioavailable testosterone” in an androgen receptor binding equation or study, or any “bioavailable” agonist value in any receptor binding equation or study.

This is because it is free testosterone concentration that is the relevant variable to binding and to activity.

Amounts bound to serum albumin and SHBG are completely irrelevant to receptor binding and to biological activity.

There are indeed popular articles, and claims by doctors, saying differently but that does not make it so.

The component of total testosterone which is bound to SHBG is completely determined by the actual free testosterone level and the amount of SHBG. The higher the SHBG figure, the more this is driven up. Is there any advantage, any increase in biological activity from being driven up this way? No.

The component of total testosterone, and the component of “bioavailable” or “free and weakly bound” testosterone which is from binding to serum albumin, is completely determined by the actual free testosterone and other binding-capable materials, principally the amount of albumin. Though fortunately serum albumin is not as variable as SHBG, still for a given actual level of free testosterone, more serum albumin gives higher “bioavailable” figure. Does its being driven up that way provide more activity? No.

The only factor relevant to activity in either instance is the actual amount of free testosterone, not the inflations in figure that result from binding to other substances.

It would be more accurate to say that various testing methods reported as free testosterone are instead fairly closely proportional to free testosterone. Different results will give different numeric values which are entirely useful when evaluated within their own reference ranges, but it’s a mistake to take a number from one lab and interpret it according to the reference range of another lab.

It’s entirely fine to use a calculated free testosterone based on total testosterone and SHBG, as the total testosterone is within reasonable margin of error almost entirely determined by actual free testosterone and the amount of SHBG.

There would be absolutely zero point to calculating a so-called “bioavailable” including the amount also that is bound to serum albumin, as the only actually relevant value is free testosterone. Or if any say there is, what is the point? What is the single peer-reviewed reference that shows albumin-bound testosterone as contributing any activity that free teststerone does not? If none, then that’s an unsupportable claim, as opposed to countless receptor binding articles which work off of free testosterone or in general free agonist levels.

This also was not the OP’s question. His doctor felt that total testosterone was what mattered and free testosterone did not. The reverse is true. Using “free and weakly bound” or “bioavailable” was not even part of his question. But having been brought up now, no, free T is the actual determinant of activity, not the amounts bound to anything else, and reported free T is properly evaluated according to the reference range of the individual laboratory. Might some laboratories do bad jobs? Sure but that is true for any test and says nothing about the biological value being measured. I don’t know about the labs in Italy but in the US free testosterone is not hard to get measured as an entirely useful value.


#12

My blood test was performed in my local hospital, with the exception of free T. For free T my blood was transferred to another lab located in the biggest hospital of Milan. This was done for FT only.


#13

[quote]Bill Roberts wrote:

I do not believe you will be able to find a single pharmacology article, published in a peer reviewed journal anywhere in the world at any time, or any pharmacology text that ever uses “bioavailable testosterone” in an androgen receptor binding equation or study, or any “bioavailable” agonist value in any receptor binding equation or study.

This is because it is free testosterone concentration that is the relevant variable to binding and to activity.[/quote]

I don’t know, you may be right, though the Mayo clinic says: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/83686

“The correlation coefficient between bioavailable and free testosterone (by equilibrium dialysis) is 0.9606. However, bioavailable testosterone is usually the preferred test, as it more closely reflects total bioactive testosterone, particularly in older men. Older men not only have elevated SHBG levels, but albumin levels also may vary due to coexisting illnesses.”

They refer to Manni A, Pardridge WM, Cefalu W, et al: Bioavailability of albumin-bound testosterone. J Clin Endocrinol Metab 1985;61:705, which is highly cited, but to which unfortunately I don’t have access right now.

In any case, they note the close correlation between free T and bio-T, so which one you measure shouldn’t matter in otherwise healthy younger men with normal albumin levels, as long as free T is measured (directly) via equilibrium dialysis. As for other ways of measuring free T, I remember Morgentaler in his book discussing the unreliability of some of them.

In any case, total T and SHBG are sufficient to calculate the rest, assuming normal albumin, so I wouldn’t even bother measuring free-T/bio-T but I would definitely want to know SHBG, which can provide useful information regarding other possible health issues. For example, low SHBG is associated with insulin resistance, while high SHBG can point to thyroid or liver problems.


#14

Highly commendable that you have a reference!

I don’t have free access now to the full article and would rather not pay for it simply to get to it sooner, but here’s the abstract anyway:[i]

J Clin Endocrinol Metab. 1985 Oct;61(4):705-10.
Bioavailability of albumin-bound testosterone.
Manni A, Pardridge WM, Cefalu W, Nisula BC, Bardin CW, Santner SJ, Santen RJ.
Abstract
The unbound fraction of plasma testosterone (T) can freely enter tissues, whereas the bioavailability of the albumin-bound T is controversial. A clinical observation in hirsute women receiving spironolactone suggested an experimental paradigm to test the effect of albumin binding on T bioavailability. We found an increase in the non-T-estrogen-binding globulin-bound fraction of plasma T in women from 24.1 +/- 3.9% to 42.0 +/- 8.1% (+/-SEM) while they received spironolactone. Computer modeling indicated that the absolute increase in the albumin-bound T concentration would be about 22.4-fold greater than that in the unbound T concentration (the ratio of albumin-bound to free T remaining virtually constant) because of the binding of T to albumin. We reasoned that the addition of graded amounts of spironolactone and its metabolites to plasma would provide a means to increase the albumin-bound T concentration appreciably. We evaluated the biological effects of this perturbation of T transport by spironolactone and its metabolites in a bioassay system using the Oldendorf technique. Bioavailable T increased proportionately with increments in free and albumin-bound T (r = 0.85; P less than 0.01). A major portion of the albumin-bound T (i.e. 55%) entered tissues under all conditions; the amount that was bioavailable vastly exceeded the amount of T that was unbound in the injected samples. An index of the amount of bioavailable T can be determined using the ammonium sulfate precipitation technique, as the percentage of non-T-estrogen-binding globulin-bound T in vitro correlated well with T bioavailability in vitro (r = 0.86; P less than 0.01). These studies support the conclusion that albumin-bound T is biologically important.[/i]

So far as I know the Oldendorf technique measures permeability, not biological activity at all in any way, as for example a reporter gene assay would do, or measurement of any in vivo biological effect would do something towards.

From the abstract there’s no indication that a different intracellular free testosterone concentration was achieved due to this permeability difference (over time I’d expect equilibrium in free T between extracellular and intracellular, as permeability is fairly good and testosterone is not consumed within the cells by interaction with the androgen receptor, and rate of conversion to metabolites is relatively low).

So it sounds to me like they found what they were looking for, but weren’t looking for anything that actually shows more androgen receptor activity or actual biological effect.

Again not to be repetitive but what’s known about receptor binding and activity, any kind of receptor, all the molecular pharmacology in this regard is based on concentration of free agonist. Amount bound is simply a function resulting from the amount of binding material together with the free concentration.

Where binding material can be especially important is where having a binding protein that changes conformation according to pH; in this instance, a xenobiotic can be picked up systemically where free concentration might be relatively low and the binding might be such that an extremely high proportion will in equilibrium be be bound rather than free, and when brought to the liver, this constant is dfiferent due to the different conformation, and a large percentage frees from the protein, resulting in locally higher free concentration in the liver and more rapid metabolic elimination. Different subject than here, and doesn’t make more serum albumin result in more biological activity of testosterone, but mentioned for the sake of not making it sound as if protein binding is always irrelevant to drug metabolism.

Another important reason is for effective distribution from point of absorption or production to the rest of the body. Here, testosterone has extremely low water solubility, and if there were no protein binding, I don’t know that it could be effectively transported from the testes given the amount of blood flow and the rate of production. With SHBG, however, the amount produced is easily transported as fast as it is produced. Again for completeness, but not causing higher serum albumin to make testosterone do more.

Basically it seems to me, from the abstract anyway, that they’re asserting by definition (or accepted asserted definition of others) that testosterone bound to serum albumin is “bioavailable,” and found that mass transport of testosterone was higher with more albumin, but did nothing to show more activity.

On the same logic, I could call testosterone dissolved in bodyfat “bioavailable” too. It most certainly will be used by the body sometime, it is available biologically to the organism as it transfers to aqueous phase, which it absolutely does all the time, in equilibrium. However, knowing the total amount dissolved in bodyfat does absolutely nothing towards aiding our knowledge of how much will happen biologically. That will be from the free testosterone.


#15

To try to simplify:

As Euclid pointed out, and probably was not the first to do so, it’s axiomatic that two things equal to the same are equal to each other.

In physical chemistry, there’s the somewhat difficult concept of “chemical potential” which is different from concentration of a solute in the solvent, but is related to it. A good analogy can be made with gravitational potential. An object will have varying amounts of gravitational potential energy depending on their altitude.

Solutes, or things, which are free to move will tend to move in a direction equalizing chemical potential, or gravitational potential for that matter.

So for example, in still conditions a lake will never have water at one end a foot higher than at the other end. At the high end, the gravitational potential will be higher. So water will have a net flow from that end to the low end, until the gravitational potential becomes equalized throughout, after which there will be no net flow from one end to the other.

Or let’s say if we had a lake adjoined with two adjacent lakes and a large channel between them, their levels will increase or decrease together with each other. If we knew the level of one of them, we’d know the level of them all.

Similarly in solution, or where you can have diffusion of a solute from A to B, including in the body, if there’s higher chemical potential at one point than another, then you get mass transport according to the difference in potential, tending extremely strongly to equalize it.

Where surface area and flow of solvent is limited, and rate of production or metabolic elimination is high, you can have a bottleneck so you might locally have a substantially higher or lower concentration at the site of production or metabolic elimination. An example would be the testes. Locally, the intratesticular free T is considerably higher than systemic free T because of this bottleneck; the difference in concentration however is what drives the mass transfer.

Relatively speaking within the rest of the body however the rates of metabolism are far lower: on the order of 100 kilos of body metabolizes what a matter of grams of testes produce, each day, so it’s a far less intensive process and mass transport is not such an issue.

Things equal to the same being equal to each other, and there being very very very free partitioning between free T in solution and bound state to albumin and bound state to SHBG, the chemical potential of free testosterone is identical to the chemical potential of testosterone as bound to serum albumin and the chemical potential of testosterone as bound to SHBG. And the receptor activation is a function of the chemical potential.

One could know any of these chemical potentials, and would know all of them, except for the fact we cannot directly measure chemical potential. However, the only directly related measurable aspect is the concentration of free T, and receptor binding equations are for this reason always (so far as I have ever seen or was taught in molecular pharmacology) from the free value. Working with a protein bound value would require additional terms and would add no information. Same free T, same receptor binding, amount of binding protein irrelevant. Though bound amount, combined with measurement of total binding protein and correct information on binding equilibrium, can enable good calculation of the free value. So all that said, a calculated free T can be perfectly good, but the process is (desirably) getting rid of the amounts bound to albumin and SHBG as those amounts are irrelevant, even if named “bioavailable” by many.

That was not as simple as I hoped: I had started out thinking it would be one paragraph, as it really does come down to “equals equal equals” but it turned out more background was needed.


#16

I spoke to another doctor yesterday, an endocrinologist and he told me the opposite of the former doctor. This one agrees with Bill Robert on FT and he told me that my testes are not probably working properly.
Anyway is not near me so i’m going to be visited by another specialist here who is curing pharmacologically a friend of mine who as i’ve said had even better values than me…


#17

That’s excellent news that you’ve found a better doctor!


#18

The new doctor put me on TRT, test e 125 mg/wk.