Free vs. Total testosterone.

Discussion in 'Men's Health Forum' started by chemman, Jan 11, 2010.

  1. chemman

    chemman Member

    Can anyone explain the value of measuring/analyzing total testosterone when it appears that total testosterone appears to be a function of the amount of SHBG present rather than HPTA output? I have read on another forum where Bill Roberts explains the rationale behind this more clearly.

    Here's the link: | When is Bioavailable T Too Low? - Page 1

    So when you have a person in a situation like mine where Total testosterone is decent (476) and free T is out of range low, does this indicate hypogonadism? Some would say that the problem is high SHBG. But based on the above thinking, it looks like SHBG is relatively static and isn't the real problem. Granted I don't have a SHBG lab (yet), but it is most likely high.

    Also, do feedback loops work on SHBG bound hormones or free?

    Thanks in advance for your input.
    Norwegian_Guy likes this.
  2. BBC3

    BBC3 Member

    The value is in the relationship. Consider Total T to be the well. The answer to your question is that IT CUTS BOTH WAYS, but only to an extent lesser than we are thinking these days. While SHBG may be one indication of how much free T is available, relationally speaking, it is still only a player in the sympony. While on the surface it would appear that only the Free T is active. This is true only to the extent of how much free T does your body need.

    I consider SHBG to be a thermostat that is getting feedback from BOTH the ACTUAL PRODUCTION RATE OF THE TESTICLES IN RELATION TO DHT AND E2 ACTION ON THE BODY. Forget about whether or not you are supplementing testosterone for a moment. You have (3) primary reasons the testicles meter production. (a) physical damage, (b) natural regulation by the body as genetic predisposed saturations of e2, and/or DHT occur, and (c) Exogenous supplementation. While ANY ONE of these factors can tell the boys to make more or less, one thing is constant, and that is the ever changing SHBG measurement. If the testicles are producing less testosterone for any one of those reasons, then the well is low. So the body now limits production of SHBG in order to make more Free Testosterone available in order to compensate. Consider the testicles are primary organs indeed. I believe there has been way too much overspeculation as to this, and this is the fact plain and simple, and applicable to a majority of all instances involving.

    In my example the Hypothalmus would be the Central Contral unit, and the Pituitary would be vector, or connecting wires to the testicles.


    Example #1: Testicles just aren't up to snuff due to injury or natural failure. Your body is most likely going to lower SHBG in order to compensate, thus giving you the same end result which is genetically mandated levels of E2, and/or DHT.

    Example #2: You are a middle aged male with body fat percentages approaching 20-30%. Your preponderance of E2 is going to shut down T production in order to limit available testosterone. Hence now your quickly responding, SHBG will again lower in order to compensate for the lack of testosterone available overall, so that the fatty tissue's learned and hardened demand for E2 can be still met.

    Example #3 You are a natural body builder. Same as the above scenerio except involving DHT to trigger this time. You body again lowers the well (TOTAL T) in order to keep you from drowning yourself in DHT. You again wind up with a lower SHBG to compensate.

    Example #4: You are supplementing Exogenous Testosterone for whatever reason. Your feedback from E2 and DHT receptors will again regulate the boys. This is the most obvious, yet convoluted situation. Your prepoderance of Total T as you fill the well with firehose of Exogenous T shuts down the testicles as you supply enough T to start an E2 and DHT world wide party at any level of SHBG. So you say now, " why would you have a low SHBG in this situation?" SImply put, the nuts are clearly the chicken and not the egg. They are producing no testosterone so SHBG goes down again.

    When I mentioned consideration for the actual functionality of individual systems I apply it as such. Consider that there are variations that can be added to the above situations, and a multiture of other situations all together that will change SHBG to high instead of low, to achieve the same result, only by means of less Free T by SHBG modulation rather that a total reduction in T. The bottom line is that in the end, you are always going to find the necessary amounts of Free T that your body requires, depending on genetics, receptor presence and capability, other potential system interactions, etc... If the body truely cant make the Free T that it needs to operate to its desired levels of DHT and E2, then something is truely fucked and this is a rare bird considering our application is AAS and Age onset HYpogonad here.

    The value of the measurement of both Total T and Free T is this. If active testosterone accounts for only about 2% of the total T count. Then how much T do you really even need? Lets say you are young with a total T of 1200 and free T levels at 1.5%, would this not be exactly the same effective end result Total T of 600 and Free T of 3%??

    Some of the ideas above are a bit radical in nature. CONSIDER THAT SHBG COUNT MAY NOT BE PROPORTIONATE TO FREE T LINEARLY, OR IF AT ALL. This could be proven in the fact that Free T rarely rises about 3.5%. The actual presetation of the physical measurements of T, free T, and SHBG are misleading to say the least. If SHBG can range up to 40 or 50 and be workable, then why would a SHBG count drop down to 12 not effect a Free t of 25% or more. It is because SHBG is more of an assistant to the availability of Free T, and not a determining factor. Consider SHBG as if it were merely a "trademark" or signpost on T available for use that this T has been marked for use.. While the drop to 12 on the SHBG measurement may indeed corrolate with more Free T. The actual number's rammifications could be considered almost impotent in relation to the actual Free T required to service the body. This rate of measurement for SHBG is hence proven of little value as presented, by the fact that it ellicits little to no VISIBLE change in the Free T percentage, while at the same time the small percentage movements effect on the body is MASSIVE. All of this is simply proves that the body can only use so much DHT or E2 depending on active and available receptors. AND IT DONT TAKE MUCH.... So now why do we have natural levels of 900 in Total T when clearly we only need 40 of them so to speak? I would claim that it is primarily a physical relation to blood volume composition as it relates to the mass of the body serviced, with also some consideration for the bodies inherent design of redundancy that protects out critical systems.. The baseline would be the fact that we all have about the same total blood volume circulating regardless of our size. There simply has to be enough T floating around to be available to make the small, yet critical conversion. Consider the actual physical measurement of SHBG. You are gonna have to put plenty of T out to deliver to all the areas where this limited hormone can activate it. You may only need 2%, but that is a large area to cover. Which finally brings us back around to testicular production of T. If the body only needs 2% of Total T to be free, Then would it not make sense that the actual slowdown of T production for any of the above listed reasons would require quite a considerable reduction in Total T to have an effect. Consider that you are living in an incideous feedback loop that is not only constantly trying to correct its self to a "known Stasis", it is trying to prevent problems as well. The older you get (high fat composition), or the more changes you make to a said "normal" system (working out adding on piles of muscle), the more you have perverted this norm. This is causing mass systemwide confusion as the body tries to adjust. The end result is the spiraling action in the direction that best solves the problems with the corruption of the natural design of the system, while at the same time mitigates the problems associated with still living at natural design levels that are now arrising due to the mounting factors now making this natural optimal profile no longer acceptable.

    In short, my Total T levels were 350 when diagnosed Hypogonadal. My free T however, was 3.5 percent. Did I ever really have a problem. Sure, I am middle aged and fat, so my Total testosterone well has been naturally reduced to a mere 350. After all my body does not want to beat its self senseless with all the E2 I was generating from this high amount of fatty tissue. But didn't I potentially have the same effective Free testosterone as I might have has at a younger Total T level of 600 or higher,, if my Free T were only 1.5 or 2% when younger? So why did my body crank Free T up? Didn't that leave me right back where I was? No. The chicken is the Testicles. A significant reduction of Total T was MANDITORY considering that it only takes 2% to function. My body would now be in a condition of E2 onslaught if my Total T were to remain high.. Just how impacting can even a .25% move on available Free T be?? Consider a Total T level of 2000. What then does a 2% level of Free T mean?? Probably your ass if it stayed there long enough!!! But at Total T of 350, the percentage means squat more than a best attempt. Then what benefit has all this provided? Not too much really. The body is pretty astute in compenstation methods. My body is now trying to get Free T back up to meet the still remaining demand for known stasis, or perhaps even a now inadvertantly reduced DHT level that is too low. THIS IS SIMPLY THE PROOF THAT THE TESTICLES ARE THE CHICKEN. "Normal" stasis now demands that the Free testosterone still be available. This two will dwindle with time, the increase in Free T is merely the second response by the body to provide previous AND LEARNED levels of available T. As the field of production and availability narrow, the game gets tougher and tighter. STASIS MUST BE FOUND. Misproportions of muscle to fat are only fuel to this fire making it worse further keeping the original harmony an impossibility, and we are left only with mitigating factors.

    I'm done. Someone correct me where I missed....

    BigPharma likes this.
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Obviously, an answer would be pages long. In the meantime, a few terms need to be defined so as to avoid confusion. As soon as you mention SHBG, the discussion includes the three main forms of testosterone transport.

    Total testosterone simply is all testosterone bound and unbound to serum proteins. The serum proteins mainly responsible for transport are SHBG and albumin.

    Free testosterone (FT) is that unbound to any serum protein. Bioavailable or non-SHBG testosterone (BT) is testosterone not bound to SHBG. So you can see, your post includes SHBG with reference to FT and TT, but not BT.

    Total testosterone has the only reproducible, validated assay used by all labs. Th other tests are method dependent and can vary considerably from lab to lab. Becuase of this do not believe or order a FT or BT unless you absolutely know the methodology and even then if it is a method known to be validated. The best recourse (and most commonly used by physicians) is to order the TT and SHBG (even the SHBG test needs to be a validated test). One can calculate the BT and FT with the Vermeulen Method.

    As far as diagnosing hypogonadism, the TT is the first test. If the TT is low (of course, a history & physical has already been done) or borderline for some, nothing else needs to be done. The TT does not do a good job of capturing all those who have hypogonadism. In the conditions where the TT is not low, one looks to the BT or FT.
  4. BBC3

    BBC3 Member

    Now There..... I knew I could bait him in for you. kinda felt bad your thread had gone so long without an answer.:rolleyes: Like I said......[:eek:)]

    I think I have some valid points, just improperly delivered.. In an ignorant sort of fashion. Thanks doc for the polite education. You clearly brought some interesting points to light further harming by self proclaimed majesty......:D
    trying to get big likes this.
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Free & Bioavailable testosterone calculator
    Check out this calculator for FT and BT. You will need TT, SHBG, and Albumin. Free & Bioavailable Testosterone calculator

    These calculated parameters more accurately reflect the level of bioactive testosterone than does the sole measurement of total serum testosterone. Testosterone and dihydrotestosterone (DHT) circulate in plasma unbound (free approximately 2 - 3%) ,bound to specific plasma proteins (sex hormone-binding globulin SHBG) and weakly bound to nonspecific proteins such as albumin. The SHBG-bound fraction is biologically inactive because of the high binding affinity of SHBG for testosterone. Free testosterone measures the free fraction, bioavailable testosterone includes free plus weakly bound to albumin.

    The following abstracts represent the frequently used Vermeulen Method of FT determination. The other abstract summarizes a more recent article exploring various algorithms for FT and BT.

    Vermeulen A, Verdonck L, Kaufman JM. A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum. J Clin Endocrinol Metab 1999;84(10):3666-72.

    The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index of bioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.

    de Ronde W, van der Schouw YT, Pols HAP, et al. Calculation of Bioavailable and Free Testosterone in Men: A Comparison of 5 Published Algorithms. Clin Chem 2006;52(9):1777-84.

    Background: Estimation of serum concentrations of free testosterone (FT) and bioavailable testosterone (bioT) by calculation is an inexpensive and uncomplicated method. We compared results obtained with 5 different algorithms. Methods: We used 5 different published algorithms [described by Sodergard et al. (bioTS and FTS), Vermeulen et al. (bioTV and FTV), Emadi-Konjin et al. (bioTE), Morris et al. (bioTM), and Ly et al. (FTL)] to estimate bioT and FT concentrations in samples obtained from 399 independently living men (ages 40-80 years) participating in a cross-sectional, single-center study. Results: Mean bioT was highest for bioTS (10.4 nmol/L) and lowest for bioTE (3.87 nmol/L). Mean FT was highest for FTS (0.41 nmol/L), followed by FTV (0.35 nmol/L), and FTL (0.29 nmol/L). For bioT concentrations, the Pearson correlation coefficient was highest for the association between bioTS and bioTV (r = 0.98) and lowest between bioTM and bioTE (r = 0.66). FTL was significantly associated with both FTS (r = 0.96) and FTV (r = 0.88). The Pearson correlation coefficient for the association between FTL and bioTM almost reached 1.0. Bland-Altman analysis showed large differences between the results of different algorithms. BioTM, bioTE, bioTV, and FTL were all significantly associated with sex hormone binding globulin (SHBG) concentrations. Conclusion: Algorithms to calculate FT and bioT must be revalidated in the local setting, otherwise over- or underestimation of FT and bioT concentrations can occur. Additionally, confounding of the results by SHBG concentrations may be introduced.
  6. TheOldFart

    TheOldFart Member

    During my nearly 2 years of diagnosed hypogonadism, I have found that FT and E2 are the most important to me. The problem is that I don't have enough test results to confirm my observations. The 4 tests that lead me to this conclusion are the following.

    July 2008 - TT = 357 (250-1100), FT = 69 (35-155), E2 = 25.6 (<20-56) - Depression was better than before, but strength, ED and libido not good.

    May 2009 - TT = 862, FT = 179, E2 = 57.2 - Depression and strength good, but ED and libido not too good.

    July 2009 - TT = 268, FT = 50, E2 = <20 - ED and libido not good at all. viagra 50 mg did almost nothing.

    October 2009 - TT = 348, FT = 101, E2 = 34.4 - Everything pretty good, probably the best in 3 or 4 years. Best of all times that I was tested.

    Now my ED is not as good as last October, but can still manage w/o Viagra. I'm guessing that my E2 is higher. The thing is that my doctor doesn't plan to order another test for 4 more months and I live in NY state and can't just get it on my own. He ordered 7 tests in 17 months and I suspect the insurance might have questioned that. I wish I could get tested at least every 2 months until I find what works best.

    By the way, there were reasons for the test differences. androgel > Testim. Changes in dose. Changes in using and amounts of Indolplex DIM and DHEA supplementation. Applying the gel right after shower vs. hours after a shower. Using nettle root extract, which is supposed to control SHBG.
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    I believe we are confusing issues. One is the diagnosis of hypogonadism. The second is the treatment. I do not think you are suggesting the diagnosis of hypogonadism be made on FT and E2. I do agree that adjustments be made to optimize TRT.
    Dr JIM likes this.
  8. TheOldFart

    TheOldFart Member

    No, I am not saying that. I'm just saying that my limited experiences indicate that FT and E2 are more important to me than TT. I was originally diagnosed with hypogonadism with a TT of 304 (250-1100). My doctor said that his experience is that most men need to be at least 500 to feel well. What surprised me was how good I felt at a TT of only 348 with my FT at 101 and E2 at 34.4. My doctor felt that as long as I was happy with the way that I felt that he was not concerned about the relatively low TT level. By the way, I am 64.
  9. chemman

    chemman Member

    Thanks for the replies! One last question... does anybody know if quest diagnostics uses equilibrium dialysis standard when ordering a free testosterone test, or do you have to specify this methodology?
  10. TheOldFart

    TheOldFart Member

    Quest has 2 tests that determine free T. One is test 14966X, which is "Testosterone, Calculated Free, Bioavailable, and Total". It tests total by liquid chromatography tandem mass spectrometry and tests for SHBG. Free T and bioavailable T are then calculated.

    The other test is 36170X, which is "Testosterone, Free and Total". It tests for total T by liquid chromatography tandem mass spectrometry and for free T by tracer equilibrium dialysis,

    I got that from the 2007 Quest manual. I am assuming that tracer equilibrium dialysis,
    calculation is not exactly the same as equilibrium dialysis, but I need someone to confirm or deny this.
  11. biceps72

    biceps72 Member

    Total testosterone doesn't have to be very high if YOU FEEL GOOD!!! e2 CAN SCREW ME UP THE WORST. I take armidex and it works!!!

    androgel is great for the libido in my experience--- actually almost too good :) When all is right, especially e2, then my erections are great; otherwise I use levitra from ADC. I am 60, work out daily (cardio and weights) ---I had ED terrible before I found out my E2 was through the roof. I feel fine with a total test of 550-800 and e2 = low 20s, my shbg = low (19-24)
  12. TheOldFart

    TheOldFart Member

    I totally agree on the E2 thing. My ED and libido were not good when my E2 was high or when it was <20. That is the problem with controlling E2. Without testing, I don't know whether to try to lower it or raise it. What really surprised me was how good I felt when my E2 and free T were reasonable, even though my total T was only 348. I guess that is why some doctors think total T is what is important, while others think it is either bioavailable T or free T. I'm thinking it is free T, which makes sense to me. The bound T isn't doing anything for me. Free T and E2 are the key. And probably DHT for libido.
  13. UFgrad777

    UFgrad777 Junior Member

    Dr. Scally- Is there any FT or BT tests that are valid in your opinion or should we just use the Vermeulen Method in all cases?

    What is the acceptable range for the Vermeulen method?

  14. tenpoundsleft

    tenpoundsleft Member

    Reviving this thread - since it has good background info, and also ended with a question. In my case, my total T came back at 883, and free T at 277. That ratio looks great - but is there such a thing as "optimal" free T in relation to total? I haven't found any info on that. Is it just absolute that counts, and if so, what's the "ideal useful" range of free T to shoot for?
  15. Dr JIM

    Dr JIM Member

    Your question belies the intent of most lab assays, which is to treat the PATIENT rather than some arbitrary numerical value MANY on Meso (esp noobs) believe is etched in stone.

    Ergo FT should NOT be used in seclusion but as a complimentary assay
    to determine ones BAT! The latter is likely the most reliable method to evaluate the NEED for TRT overall.
    However it's also important to remember DHT the most powerful male androgen is not even included in the BAT

    Why in the past week alone we have several new threads where OPs want to "discuss" how close their normal tests is to abnormal!

    The implication being normal is not normal but perhaps abnorma in those who need a scapegoat for their underlying psychiatric ailments.
    Last edited: Oct 10, 2015
  16. tenpoundsleft

    tenpoundsleft Member

    Presumably you're replying to my question?

    I was just wondering "is there such a thing as "optimal" free T in relation to total?" - note "is there" - so the answer is no?

    I have no interest in what is normal or abnormal - just what is optimal, if there is such a thing.
  17. Dr JIM

    Dr JIM Member

    And that's my point, much like TT, DHT, and E-2 etc there are generally accepted RANGES, such as a fT being 1-2% of TT, which confer specific benefits.

    However what is "optimal" may infer something more such as a specific numerical value exclusive of established reference ranges, and that slippery slope must be avoided.
  18. tenpoundsleft

    tenpoundsleft Member

    Fair enough - although I think most of are looking to optimize (not maximize), i.e. get to a level where benefits still outweigh sides.

    Can you explain my results? Total T: 883, and Free T: 277 - that sounds crazy high. If Free T is supposed to be below 2 percent of Total T, then my Free T should be below 18%, but its 277! And this was from blood drawn three days post Cyp injection. Granted, heavy on several peptides still, is that the reason?
  19. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Seriously!!! You are comparing the expected values for a normal distribution of healthy males to that on TC!!! Seriously!!!
    Dr JIM likes this.
  20. tenpoundsleft

    tenpoundsleft Member

    Yes, what's wrong with that? It's not like I'm on a cycle going for supra-physiological levels - I'm on TRT....

    It's supposed to be REPLACEMENT - i.e. get me to the same level as that found in the "normal distribution of healthy males" - which the Total Test level appears to have succeeded in hitting just right. I'm just trying to figure out why the Free Test level seems so high. I don't mind it being high, having a decent Free Test level is what we all want, right?

    Can't you be more constructive, and not quite so snarky? As an MD, you presumably know this way more than I will ever do. If you were asking me about my field of expertise (supply chain) I would explain and not dismiss sincerely asked questions.