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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
Reference Intervals for Free Testosterone in Adult Men Measured Using a Standardized Equilibrium Dialysis Procedure
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<blockquote data-quote="madman" data-source="post: 236962" data-attributes="member: 13851"><p>Better yet fetch them yourself next time before everyone starts running their mouths!</p><p></p><p>This is where it stands as of now!</p><p></p><p><a href="https://www.excelmale.com/forum/threads/how-accurate-is-the-online-tru-t-free-test-calculator.26260/#post-236061" target="_blank">How Accurate Is The Online Tru-T Free Test. Calculator?</a></p><p></p><p></p><p>Yet 4 years since the Fiers study let alone the most recent data which they have been sitting on and Bhasin continues to hammer this home!</p><p></p><p></p><p><strong>Bhasin:</strong></p><p><strong></strong></p><p><strong><em><strong><em>*the Vermeulen equation and others that assume a fixed Kd are just conceptually wrong and our data show it clearly that this model is completely wrong</em></strong></em></strong></p><p><strong><em><strong><em></em></strong></em></strong></p><p><strong><em><strong><em>*so the Vermeulen model or most of the linear equations underestimate free testosterone concentrations and the ensemble allosteric model (EAM) based upon our experimental data matches total testosterone within the range in which we have validated this</em></strong></em></strong></p><p><strong><em></em></strong></p><p><strong><em>*Recent studies using modern biophysical techniques have shown that the binding of testosterone and estradiol to SHBG is a dynamic nonlinear process that involves an allosteric interaction between the 2 SHBG monomers, such that the Kd varies dynamically across the range of sex hormone and SHBG concentrations</em></strong></p><p></p><p></p><p></p><p></p><p>Remember what I said about everyone and their brother waiting on the results/data from Phase II which still is ongoing?</p><p></p><p>Aim 3 who knew?</p><p></p><p></p><p><strong><em>*In phase I studies, we demonstrated that the TruTTM algorithm provides accurate free T values that match those obtained using the equilibrium dialysis in healthy and hypogonadal men. We have also shown that the binding parameters that have formed the basis of previous equations (e.g., Vermeulen) are incorrect, and that free T values derived using these equations deviate substantially from free T measured by equilibrium dialysis. The phase I studies have led to the adoption of the TruTTM algorithm at several institutions</em></strong></p><p></p><p><em><strong>*<u>The</u></strong><u><strong> phase II program</strong> <strong>will continue the development of the TruTTM algorithm by validating it in common conditions characterized by altered SHBG concentrations</strong></u><strong><u>, such as obesity and aging</u> (AIM 1), <u>in healthy women across the menstrual cycle, and in women with PCOS</u> (Aim 2). <u>We will generate population-based reference ranges for free T (Aim 3)</u>. Phase II also includes plans for the commercialization of the TruTTM algorithm using a HIPAA-compliant infrastructure for its clinical adoption</strong></em></p><p></p><p></p><p></p><p></p><p>He has not changed his stance and is still pushing the newer EAM (cFTZ/TruTTM)!</p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/whats-coming-accurate-measurement-of-total-and-free-testosterone-levels-for-the-diagnosis-of-androgen-disorders.25690/[/URL]</p><p></p><p><em><em><em><em><strong>*<em>Testosterone levels should be measured preferably in a CDCcertified laboratory using validated assays; in cases of equivocal TT concentration and/or abnormal SHBG levels, free testosterone levels should be measured using equilibrium dialysis or <u>calculated using an equation based on our current understanding of the dynamics of testosterone binding, such as the ensemble allostery model</u></em></strong></em></em></em></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/improving-diagnostic-accuracy-and-treatment-decisions-in-men-with-hypogonadism.24968/[/URL]</p><p></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/testosterone-deficiency-in-men.24722/[/URL]</p><p></p><p><em><strong>*<u>Free testosterone concentration is ideally measured using the equilibrium dialysis method, performed under standardized conditions</u>.1,31<u> Direct tracer analog methods for measuring free testosterone concentrations are inaccurate, and therefore, their use is not recommended</u>.35 Although several equations to estimate free testosterone concentration from total testosterone, SHBG, and albumin concentrations have been published,36-38 the estimation of free testosterone concentration performed using these equations are predicated upon accurate measurements of total testosterone, SHBG, and albumin concentrations.31,35 <u>Furthermore, equations that are based on a linear model of testosterone’s binding to SHBG assume a fixed binding affinity (approximately 1 nM)31 and ignore the competing presence of other sex steroids, such as dihydrotestosterone and estradiol</u>.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Recent studies using modern biophysical techniques have suggested that the <u>binding of testosterone and estradiol to an SHBG dimer is a dynamic process that involves allosteric interactions between binding sites on each of the 2 SHBG monomers such that the binding affinities of the 2 sites are not equivalent</u>.36,39 <u>The binding of a ligand to the first monomer influences the conformational and energetic states of both the monomers</u>.39 <u>The estimation of free testosterone concentration based on an ensemble allosteric model provides a close approximation of concentrations measured using equilibrium dialysis</u>36</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*<u>the computations of free testosterone concentrations using the ensemble allostery model can be obtained at <a href="https://tru-t.org/" target="_blank">TruT Free Testosterone Calculator by FPT</a></u>. Because of dynamic changes in the binding affinity of SHBG upon ligand binding, depending on the ligand and SHBG concentrations, <u>no equation can accurately estimate free testosterone concentration under all conditions</u>.39</strong></em></p></blockquote><p></p>
[QUOTE="madman, post: 236962, member: 13851"] Better yet fetch them yourself next time before everyone starts running their mouths! This is where it stands as of now! [URL='https://www.excelmale.com/forum/threads/how-accurate-is-the-online-tru-t-free-test-calculator.26260/#post-236061']How Accurate Is The Online Tru-T Free Test. Calculator?[/URL] Yet 4 years since the Fiers study let alone the most recent data which they have been sitting on and Bhasin continues to hammer this home! [B]Bhasin: [I][B][I]*the Vermeulen equation and others that assume a fixed Kd are just conceptually wrong and our data show it clearly that this model is completely wrong *so the Vermeulen model or most of the linear equations underestimate free testosterone concentrations and the ensemble allosteric model (EAM) based upon our experimental data matches total testosterone within the range in which we have validated this[/I][/B] *Recent studies using modern biophysical techniques have shown that the binding of testosterone and estradiol to SHBG is a dynamic nonlinear process that involves an allosteric interaction between the 2 SHBG monomers, such that the Kd varies dynamically across the range of sex hormone and SHBG concentrations[/I][/B] Remember what I said about everyone and their brother waiting on the results/data from Phase II which still is ongoing? Aim 3 who knew? [B][I]*In phase I studies, we demonstrated that the TruTTM algorithm provides accurate free T values that match those obtained using the equilibrium dialysis in healthy and hypogonadal men. We have also shown that the binding parameters that have formed the basis of previous equations (e.g., Vermeulen) are incorrect, and that free T values derived using these equations deviate substantially from free T measured by equilibrium dialysis. The phase I studies have led to the adoption of the TruTTM algorithm at several institutions[/I][/B] [I][B]*[U]The[/U][/B][U][B] phase II program[/B] [B]will continue the development of the TruTTM algorithm by validating it in common conditions characterized by altered SHBG concentrations[/B][/U][B][U], such as obesity and aging[/U] (AIM 1), [U]in healthy women across the menstrual cycle, and in women with PCOS[/U] (Aim 2). [U]We will generate population-based reference ranges for free T (Aim 3)[/U]. Phase II also includes plans for the commercialization of the TruTTM algorithm using a HIPAA-compliant infrastructure for its clinical adoption[/B][/I] He has not changed his stance and is still pushing the newer EAM (cFTZ/TruTTM)! [URL unfurl="true"]https://www.excelmale.com/forum/threads/whats-coming-accurate-measurement-of-total-and-free-testosterone-levels-for-the-diagnosis-of-androgen-disorders.25690/[/URL] [I][I][I][I][B]*[I]Testosterone levels should be measured preferably in a CDCcertified laboratory using validated assays; in cases of equivocal TT concentration and/or abnormal SHBG levels, free testosterone levels should be measured using equilibrium dialysis or [U]calculated using an equation based on our current understanding of the dynamics of testosterone binding, such as the ensemble allostery model[/U][/I][/B][/I][/I][/I][/I] [URL unfurl="true"]https://www.excelmale.com/forum/threads/improving-diagnostic-accuracy-and-treatment-decisions-in-men-with-hypogonadism.24968/[/URL] [URL unfurl="true"]https://www.excelmale.com/forum/threads/testosterone-deficiency-in-men.24722/[/URL] [I][B]*[U]Free testosterone concentration is ideally measured using the equilibrium dialysis method, performed under standardized conditions[/U].1,31[U] Direct tracer analog methods for measuring free testosterone concentrations are inaccurate, and therefore, their use is not recommended[/U].35 Although several equations to estimate free testosterone concentration from total testosterone, SHBG, and albumin concentrations have been published,36-38 the estimation of free testosterone concentration performed using these equations are predicated upon accurate measurements of total testosterone, SHBG, and albumin concentrations.31,35 [U]Furthermore, equations that are based on a linear model of testosterone’s binding to SHBG assume a fixed binding affinity (approximately 1 nM)31 and ignore the competing presence of other sex steroids, such as dihydrotestosterone and estradiol[/U]. *Recent studies using modern biophysical techniques have suggested that the [U]binding of testosterone and estradiol to an SHBG dimer is a dynamic process that involves allosteric interactions between binding sites on each of the 2 SHBG monomers such that the binding affinities of the 2 sites are not equivalent[/U].36,39 [U]The binding of a ligand to the first monomer influences the conformational and energetic states of both the monomers[/U].39 [U]The estimation of free testosterone concentration based on an ensemble allosteric model provides a close approximation of concentrations measured using equilibrium dialysis[/U]36 *[U]the computations of free testosterone concentrations using the ensemble allostery model can be obtained at [URL='https://tru-t.org/']TruT Free Testosterone Calculator by FPT[/URL][/U]. Because of dynamic changes in the binding affinity of SHBG upon ligand binding, depending on the ligand and SHBG concentrations, [U]no equation can accurately estimate free testosterone concentration under all conditions[/U].39[/B][/I] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
Reference Intervals for Free Testosterone in Adult Men Measured Using a Standardized Equilibrium Dialysis Procedure
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