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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Reassessing Free-Testosterone Calculation by Liquid Chromatography–Tandem Mass Spectrometry Direct Equilibrium Dialysis
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<blockquote data-quote="tareload" data-source="post: 189329"><p>Surprised no additional discussion on this one. Vermeulen hanging in there vs other methods.</p><p></p><p></p><p>[ATTACH=full]11192[/ATTACH]</p><p></p><p></p><p>[ATTACH=full]11193[/ATTACH]</p><p></p><p></p><p><span style="font-size: 18px"><strong>Calculated estimations of FT</strong></span></p><p></p><p>FT level was calculated from total T, SHBG and albumin serum levels according to the three following methods: (1) an equation based on the law of mass action as published by Vermeulen <em>et al.</em> (<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">8</a>) (cFT-V); (2) two empirically derived formulae (for men, the formula for T > 5 nM was used; for women, the formula <5 nM was used) as published by Ly and Handelsman (<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">15</a>) (cFT-L); and (3) according to a calculation based on a multistep, dynamic, allosteric model of testosterone binding to SHBG as published by Zakharov <em>et al.</em> (<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">17</a>) (cFT-Z). The values for cFT-Z from the EMAS samples (calculated with original T and SHBG from EMAS) were provided by Dr. R. Jasuja, Boston, MA, to the EMAS investigators. We had no direct access to the algorithm for cFT-Z; therefore, we were unable to present any data on cFT-Z for the samples from SIBLOS and from women.</p><p></p><p> </p><p></p><p><span style="font-size: 18px"><strong>Calculated estimates of FT</strong></span></p><p></p><p>The cFT-Z values reported here have been supplied by the authors who reported data for cFT-Z in the EMAS cohort in the publication describing their multistep, dynamic, allosteric model to calculate FT (<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">17</a>). We requested access to the cFT-Z algorithm from the research group that developed this allosteric model algorithm. However, at the time of completion of this work, we had not been able to gain direct access to the algorithm. Therefore, it was not possible to make comparisons with cFT-Z for all three cohorts. This is a limitation of the current study that is beyond our control. We felt it important to evaluate cFT-Z in the current study because the results obtained by the authors according to their allosteric model to replicate the dimeric binding of T to SHBG differed substantially from the model based on the law of mass action (<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">4</a>, <a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">17</a>). Using the allosteric model, they reported higher FT% in men of 3% to 5% and that cFT-V substantially underestimated FT compared with their findings for FT by dialysis (<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">17</a>). Our results for the EMAS samples, indeed, do reproduce their finding that cFT-Z values are markedly higher than cFT-V values. Similarly, cFT-Z values are much higher compared with cFT-L. However, in contrast to their findings, our results also show that cFT-Z is markedly higher (about double) compared with FT measured by direct ED. Moreover, accuracy of cFT-Z as reflected in the ratio of cFT-Z over measured FT was strongly dependent on serum SHBG levels and, to a lesser degree, on T and albumin levels. At present, it is unclear what underlies the apparent discrepancy between the results reported by Zakharov <em>et al.</em> (<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">17</a>) and the findings in the current study performed on a same set of samples. A factor involved may be differences in ED methods between laboratories giving discrepant measured FT results. The descriptive nature of this study does not allow us to address possible merits or demerits of basic assumptions on which the allosteric model is based.</p></blockquote><p></p>
[QUOTE="tareload, post: 189329"] Surprised no additional discussion on this one. Vermeulen hanging in there vs other methods. [ATTACH type="full"]11192[/ATTACH] [ATTACH type="full"]11193[/ATTACH] [SIZE=18px][B]Calculated estimations of FT[/B][/SIZE] FT level was calculated from total T, SHBG and albumin serum levels according to the three following methods: (1) an equation based on the law of mass action as published by Vermeulen [I]et al.[/I] ([URL='https://www.excelmale.com/forum/javascript%3A;']8[/URL]) (cFT-V); (2) two empirically derived formulae (for men, the formula for T > 5 nM was used; for women, the formula <5 nM was used) as published by Ly and Handelsman ([URL='https://www.excelmale.com/forum/javascript%3A;']15[/URL]) (cFT-L); and (3) according to a calculation based on a multistep, dynamic, allosteric model of testosterone binding to SHBG as published by Zakharov [I]et al.[/I] ([URL='https://www.excelmale.com/forum/javascript%3A;']17[/URL]) (cFT-Z). The values for cFT-Z from the EMAS samples (calculated with original T and SHBG from EMAS) were provided by Dr. R. Jasuja, Boston, MA, to the EMAS investigators. We had no direct access to the algorithm for cFT-Z; therefore, we were unable to present any data on cFT-Z for the samples from SIBLOS and from women. [SIZE=18px][B]Calculated estimates of FT[/B][/SIZE] The cFT-Z values reported here have been supplied by the authors who reported data for cFT-Z in the EMAS cohort in the publication describing their multistep, dynamic, allosteric model to calculate FT ([URL='https://www.excelmale.com/forum/javascript%3A;']17[/URL]). We requested access to the cFT-Z algorithm from the research group that developed this allosteric model algorithm. However, at the time of completion of this work, we had not been able to gain direct access to the algorithm. Therefore, it was not possible to make comparisons with cFT-Z for all three cohorts. This is a limitation of the current study that is beyond our control. We felt it important to evaluate cFT-Z in the current study because the results obtained by the authors according to their allosteric model to replicate the dimeric binding of T to SHBG differed substantially from the model based on the law of mass action ([URL='https://www.excelmale.com/forum/javascript%3A;']4[/URL], [URL='https://www.excelmale.com/forum/javascript%3A;']17[/URL]). Using the allosteric model, they reported higher FT% in men of 3% to 5% and that cFT-V substantially underestimated FT compared with their findings for FT by dialysis ([URL='https://www.excelmale.com/forum/javascript%3A;']17[/URL]). Our results for the EMAS samples, indeed, do reproduce their finding that cFT-Z values are markedly higher than cFT-V values. Similarly, cFT-Z values are much higher compared with cFT-L. However, in contrast to their findings, our results also show that cFT-Z is markedly higher (about double) compared with FT measured by direct ED. Moreover, accuracy of cFT-Z as reflected in the ratio of cFT-Z over measured FT was strongly dependent on serum SHBG levels and, to a lesser degree, on T and albumin levels. At present, it is unclear what underlies the apparent discrepancy between the results reported by Zakharov [I]et al.[/I] ([URL='https://www.excelmale.com/forum/javascript%3A;']17[/URL]) and the findings in the current study performed on a same set of samples. A factor involved may be differences in ED methods between laboratories giving discrepant measured FT results. The descriptive nature of this study does not allow us to address possible merits or demerits of basic assumptions on which the allosteric model is based. [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Reassessing Free-Testosterone Calculation by Liquid Chromatography–Tandem Mass Spectrometry Direct Equilibrium Dialysis
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