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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
Calculate Free Testosterone with TruT by FPT
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<blockquote data-quote="madman" data-source="post: 145412" data-attributes="member: 13851"><p>We would need to keep this in mind.</p><p></p><p><strong>Assessment of free testosterone concentration <span style="color: rgb(184, 49, 47)">(2019)</span></strong></p><p></p><p><span style="color: rgb(184, 49, 47)"><strong>Brian G Keevil, Jo Adaway </strong></span></p><p></p><p></p><p><strong><span style="color: rgb(184, 49, 47)">Highlights</span> </strong></p><p><strong></strong></p><p><strong> Free testosterone may complement the measurement of total serum T, but this view remains controversial and is not universally accepted </strong></p><p></p><p> <strong>Equilibrium dialysis methods are too complex for routine clinical use</strong></p><p></p><p> <strong><span style="color: rgb(184, 49, 47)">Equations for calculating free testosterone</span> <span style="color: rgb(184, 49, 47)">are </span><span style="color: rgb(41, 105, 176)">inaccurate</span><span style="color: rgb(184, 49, 47)"> because they were founded on</span><span style="color: rgb(41, 105, 176)"> faulty models of T binding to SHBG</span></strong></p><p></p><p> T<strong>he free androgen index is not recommended for use in males or females because of inaccuracy when the SHBG concentration is low.</strong></p><p></p><p> <strong><span style="color: rgb(184, 49, 47)">More </span><span style="color: rgb(41, 105, 176)">accurate equations</span><span style="color: rgb(184, 49, 47)"> are needed </span><span style="color: rgb(41, 105, 176)">to calculate free testosterone</span><span style="color: rgb(184, 49, 47)">, based on </span><span style="color: rgb(41, 105, 176)">more detailed knowledge</span><span style="color: rgb(184, 49, 47)"> of </span><span style="color: rgb(41, 105, 176)">the binding of testosterone to SHBG.</span></strong></p><p></p><p> <strong>Harmonization of T and SHBG assays between laboratories needs to be improved </strong></p><p></p><p></p><p><span style="color: rgb(184, 49, 47)"><strong>*</strong></span><strong>The <span style="color: rgb(184, 49, 47)">algorithms derived for calculating free T</span> are <span style="color: rgb(184, 49, 47)">inaccurate </span>because they were founded <span style="color: rgb(41, 105, 176)">on faulty models</span><span style="color: rgb(184, 49, 47)"> of </span><span style="color: rgb(41, 105, 176)">testosterone binding to SHBG</span></strong></p><p></p><p><span style="color: rgb(226, 80, 65)"><strong>*</strong></span><strong>the<span style="color: rgb(41, 105, 176)"> effects</span> <span style="color: rgb(0, 0, 0)">of </span><span style="color: rgb(41, 105, 176)">differences</span> <span style="color: rgb(41, 105, 176)">in binding protein constants</span></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>The calculation proposed by <span style="color: rgb(184, 49, 47)">Vermeulen</span> et al has been the most widely used but the <span style="color: rgb(184, 49, 47)">main criticism of all these equations</span> is that <span style="color: rgb(184, 49, 47)">the model of binding of T to SHBG may not be accurate</span>, and in addition <span style="color: rgb(41, 105, 176)">the set of binding constants used</span> may not be appropriate (14, 32). </strong>SHBG is a homodimeric glycoprotein with a molecular weight of approximately 90 kDa (33) and the distribution of testosterone bound to SHBG is different in males and females. When Estradiol is present, approximately 20% of SHBG binding sites are occupied by testosterone (34). <strong>It was previously thought that <span style="color: rgb(184, 49, 47)">the two binding sites on the SHBG molecule are equivalent</span></strong>, <strong>but using <span style="color: rgb(184, 49, 47)">modern biophysical techniques</span> it is now known that <span style="color: rgb(41, 105, 176)">the binding sites are not equivalent</span>, and <span style="color: rgb(41, 105, 176)">they each bind SHBG with a different affinity </span>(22).</strong> As a result of this, alternative models of binding of T to SHBG have been advocated (14,22).</p><p></p><p></p><p></p><p><strong><span style="color: rgb(184, 49, 47)">Calculated FT (cFT) estimates</span> are based on the assumption that <span style="color: rgb(184, 49, 47)">there is normal steady-state protein binding for T </span>and the equations are dependent on reliability and accuracy of both the T and SHBG assays (6, 35, 36).</strong> <strong><span style="color: rgb(184, 49, 47)">All of the equations</span> will <span style="color: rgb(184, 49, 47)">estimate free T incorrectly</span> when <span style="color: rgb(184, 49, 47)">the protein concentrations differ widely from physiological values</span>, if there are<span style="color: rgb(184, 49, 47)"> large concentrations of competing steroids</span>, or if <span style="color: rgb(184, 49, 47)">the SHBG binding affinity</span> is affected by <span style="color: rgb(184, 49, 47)">a rare genetic variant (12, 37).</span> </strong>Depending on the equation used, systematic differences between free T estimates have been reported compared with measured free T (18, 21, 30). <strong><span style="color: rgb(184, 49, 47)">Discrepancies </span>between <span style="color: rgb(184, 49, 47)">free T measured using equilibrium dialysis</span> and <span style="color: rgb(184, 49, 47)">cFT </span>are most likely caused by <span style="color: rgb(41, 105, 176)">erroneous modelling of testosterone binding to SHBG. </span></strong></p><p></p><p></p><p>Recent work shows that cFT-Vermeulen is strongly correlated to free T measured by the reference method (direct equilibrium dialysis),<strong> but <span style="color: rgb(184, 49, 47)">free T is overestimated</span> by <span style="color: rgb(184, 49, 47)">20 to 30%</span>, thus agreeing with previous work (21, 38, 39).</strong><span style="color: rgb(184, 49, 47)"> <strong>However, the relationship between </strong></span><span style="color: rgb(0, 0, 0)"><strong>cFT-Vermeulen and measured free T</strong></span><span style="color: rgb(184, 49, 47)"><strong> was found to be</strong></span><span style="color: rgb(0, 0, 0)"><strong> linear and independent </strong></span><span style="color: rgb(184, 49, 47)"><strong>of </strong></span><span style="color: rgb(0, 0, 0)"><strong>serum T, albumin and SHBG concentrations.</strong></span> <strong><span style="color: rgb(184, 49, 47)">The</span> <span style="color: rgb(184, 49, 47)">lack of reliance on SHBG in the Vermeulen equation </span>was thought to be <span style="color: rgb(184, 49, 47)">strength of the cFT-Vermeulen</span> since assessment of free T is especially important in patients at<span style="color: rgb(184, 49, 47)"> the extremes of the SHBG concentration range. </span></strong><span style="color: rgb(0, 0, 0)"><strong>The </strong></span><span style="color: rgb(41, 105, 176)"><strong>bias</strong></span><span style="color: rgb(0, 0, 0)"><strong> is probably due </strong></span><span style="color: rgb(41, 105, 176)"><strong>to imperfect estimations of the association constants for the binding of T to SHBG and albumin</strong></span><span style="color: rgb(0, 0, 0)"><strong>, as discussed above, and this would need to be allowed for when comparing different methods for cFT.</strong></span></p><p></p><p></p><p><strong><span style="color: rgb(184, 49, 47)">Equations for calculating FT</span> are <span style="color: rgb(184, 49, 47)">inaccurate </span>because they were <span style="color: rgb(184, 49, 47)">founded on faulty models</span> of <span style="color: rgb(41, 105, 176)">T binding to SHBG.</span></strong> Calculated FT methods offer are simple and inexpensive and may offer the best way forward, <strong>but <span style="color: rgb(184, 49, 47)">more accurate equations</span> are needed and these must be based on <span style="color: rgb(184, 49, 47)">more detailed knowledge</span> of <span style="color: rgb(41, 105, 176)">the complicated binding testosterone to SHBG. </span></strong></p></blockquote><p></p>
[QUOTE="madman, post: 145412, member: 13851"] We would need to keep this in mind. [B]Assessment of free testosterone concentration [COLOR=rgb(184, 49, 47)](2019)[/COLOR][/B] [COLOR=rgb(184, 49, 47)][B]Brian G Keevil, Jo Adaway [/B][/COLOR] [B][COLOR=rgb(184, 49, 47)]Highlights[/COLOR] Free testosterone may complement the measurement of total serum T, but this view remains controversial and is not universally accepted [/B] [B]Equilibrium dialysis methods are too complex for routine clinical use[/B] [B][COLOR=rgb(184, 49, 47)]Equations for calculating free testosterone[/COLOR] [COLOR=rgb(184, 49, 47)]are [/COLOR][COLOR=rgb(41, 105, 176)]inaccurate[/COLOR][COLOR=rgb(184, 49, 47)] because they were founded on[/COLOR][COLOR=rgb(41, 105, 176)] faulty models of T binding to SHBG[/COLOR][/B] T[B]he free androgen index is not recommended for use in males or females because of inaccuracy when the SHBG concentration is low.[/B] [B][COLOR=rgb(184, 49, 47)]More [/COLOR][COLOR=rgb(41, 105, 176)]accurate equations[/COLOR][COLOR=rgb(184, 49, 47)] are needed [/COLOR][COLOR=rgb(41, 105, 176)]to calculate free testosterone[/COLOR][COLOR=rgb(184, 49, 47)], based on [/COLOR][COLOR=rgb(41, 105, 176)]more detailed knowledge[/COLOR][COLOR=rgb(184, 49, 47)] of [/COLOR][COLOR=rgb(41, 105, 176)]the binding of testosterone to SHBG.[/COLOR][/B] [B]Harmonization of T and SHBG assays between laboratories needs to be improved [/B] [COLOR=rgb(184, 49, 47)][B]*[/B][/COLOR][B]The [COLOR=rgb(184, 49, 47)]algorithms derived for calculating free T[/COLOR] are [COLOR=rgb(184, 49, 47)]inaccurate [/COLOR]because they were founded [COLOR=rgb(41, 105, 176)]on faulty models[/COLOR][COLOR=rgb(184, 49, 47)] of [/COLOR][COLOR=rgb(41, 105, 176)]testosterone binding to SHBG[/COLOR][/B] [COLOR=rgb(226, 80, 65)][B]*[/B][/COLOR][B]the[COLOR=rgb(41, 105, 176)] effects[/COLOR] [COLOR=rgb(0, 0, 0)]of [/COLOR][COLOR=rgb(41, 105, 176)]differences[/COLOR] [COLOR=rgb(41, 105, 176)]in binding protein constants[/COLOR] The calculation proposed by [COLOR=rgb(184, 49, 47)]Vermeulen[/COLOR] et al has been the most widely used but the [COLOR=rgb(184, 49, 47)]main criticism of all these equations[/COLOR] is that [COLOR=rgb(184, 49, 47)]the model of binding of T to SHBG may not be accurate[/COLOR], and in addition [COLOR=rgb(41, 105, 176)]the set of binding constants used[/COLOR] may not be appropriate (14, 32). [/B]SHBG is a homodimeric glycoprotein with a molecular weight of approximately 90 kDa (33) and the distribution of testosterone bound to SHBG is different in males and females. When Estradiol is present, approximately 20% of SHBG binding sites are occupied by testosterone (34). [B]It was previously thought that [COLOR=rgb(184, 49, 47)]the two binding sites on the SHBG molecule are equivalent[/COLOR][/B], [B]but using [COLOR=rgb(184, 49, 47)]modern biophysical techniques[/COLOR] it is now known that [COLOR=rgb(41, 105, 176)]the binding sites are not equivalent[/COLOR], and [COLOR=rgb(41, 105, 176)]they each bind SHBG with a different affinity [/COLOR](22).[/B] As a result of this, alternative models of binding of T to SHBG have been advocated (14,22). [B][COLOR=rgb(184, 49, 47)]Calculated FT (cFT) estimates[/COLOR] are based on the assumption that [COLOR=rgb(184, 49, 47)]there is normal steady-state protein binding for T [/COLOR]and the equations are dependent on reliability and accuracy of both the T and SHBG assays (6, 35, 36).[/B] [B][COLOR=rgb(184, 49, 47)]All of the equations[/COLOR] will [COLOR=rgb(184, 49, 47)]estimate free T incorrectly[/COLOR] when [COLOR=rgb(184, 49, 47)]the protein concentrations differ widely from physiological values[/COLOR], if there are[COLOR=rgb(184, 49, 47)] large concentrations of competing steroids[/COLOR], or if [COLOR=rgb(184, 49, 47)]the SHBG binding affinity[/COLOR] is affected by [COLOR=rgb(184, 49, 47)]a rare genetic variant (12, 37).[/COLOR] [/B]Depending on the equation used, systematic differences between free T estimates have been reported compared with measured free T (18, 21, 30). [B][COLOR=rgb(184, 49, 47)]Discrepancies [/COLOR]between [COLOR=rgb(184, 49, 47)]free T measured using equilibrium dialysis[/COLOR] and [COLOR=rgb(184, 49, 47)]cFT [/COLOR]are most likely caused by [COLOR=rgb(41, 105, 176)]erroneous modelling of testosterone binding to SHBG. [/COLOR][/B] Recent work shows that cFT-Vermeulen is strongly correlated to free T measured by the reference method (direct equilibrium dialysis),[B] but [COLOR=rgb(184, 49, 47)]free T is overestimated[/COLOR] by [COLOR=rgb(184, 49, 47)]20 to 30%[/COLOR], thus agreeing with previous work (21, 38, 39).[/B][COLOR=rgb(184, 49, 47)] [B]However, the relationship between [/B][/COLOR][COLOR=rgb(0, 0, 0)][B]cFT-Vermeulen and measured free T[/B][/COLOR][COLOR=rgb(184, 49, 47)][B] was found to be[/B][/COLOR][COLOR=rgb(0, 0, 0)][B] linear and independent [/B][/COLOR][COLOR=rgb(184, 49, 47)][B]of [/B][/COLOR][COLOR=rgb(0, 0, 0)][B]serum T, albumin and SHBG concentrations.[/B][/COLOR] [B][COLOR=rgb(184, 49, 47)]The[/COLOR] [COLOR=rgb(184, 49, 47)]lack of reliance on SHBG in the Vermeulen equation [/COLOR]was thought to be [COLOR=rgb(184, 49, 47)]strength of the cFT-Vermeulen[/COLOR] since assessment of free T is especially important in patients at[COLOR=rgb(184, 49, 47)] the extremes of the SHBG concentration range. [/COLOR][/B][COLOR=rgb(0, 0, 0)][B]The [/B][/COLOR][COLOR=rgb(41, 105, 176)][B]bias[/B][/COLOR][COLOR=rgb(0, 0, 0)][B] is probably due [/B][/COLOR][COLOR=rgb(41, 105, 176)][B]to imperfect estimations of the association constants for the binding of T to SHBG and albumin[/B][/COLOR][COLOR=rgb(0, 0, 0)][B], as discussed above, and this would need to be allowed for when comparing different methods for cFT.[/B][/COLOR] [B][COLOR=rgb(184, 49, 47)]Equations for calculating FT[/COLOR] are [COLOR=rgb(184, 49, 47)]inaccurate [/COLOR]because they were [COLOR=rgb(184, 49, 47)]founded on faulty models[/COLOR] of [COLOR=rgb(41, 105, 176)]T binding to SHBG.[/COLOR][/B] Calculated FT methods offer are simple and inexpensive and may offer the best way forward, [B]but [COLOR=rgb(184, 49, 47)]more accurate equations[/COLOR] are needed and these must be based on [COLOR=rgb(184, 49, 47)]more detailed knowledge[/COLOR] of [COLOR=rgb(41, 105, 176)]the complicated binding testosterone to SHBG. [/COLOR][/B] [/QUOTE]
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