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Open Access Published by De Gruyter December 12, 2006

Impact of recent biochemical findings on the determination of free and bioavailable testosterone: evaluation and proposal for clinical use / Auswirkungen neuer biochemischer Befunde auf die Bestimmung von freiem und bioverfügbarem Testosteron: Evaluierung und Vorschlag für den klinischen Einsatz

  • Joerg Hasler , Roberto Herklotz , Peter B. Luppa , Michael J. Diver , Mario Thevis , Jochen Metzger , Reto Savoca , Fernando Jermini and Andreas R. Huber
From the journal LaboratoriumsMedizin

Abstract

Background: The mass action law-based calculation methods for free testosterone (FT) and “bioavailable” testosterone (BAT) – routinely used for assessing androgen disorders – rely on the supposition that the sex hormone binding globulin (SHBG) molecule contains one steroid binding domain (SBD). However, recent biochemical investigations revealed that this molecule actually comprises two SBDs. This necessitates new equations (Calc2) for FT and BAT calculation.

Methods and results: Calc2 was deduced using the recently published SHBG-testosterone association constant and was compared to other FT and/or BAT determination methods (e.g., a conventional calculation version [CalcV], ammonium sulfate precipitation [for measuring BAT] relying on total testosterone [TT] by mass spectrometry, and a FT radioimmunoassay [RIA] proving satisfactory). In contrast to CalcV BAT, Calc2 BAT fitted ammonium sulfate precipitation BAT. An analogous result was found by means of a comparison of FT ratios determined by RIA, Calc2, and CalcV, respectively. Additionally, Calc2 data mostly appear to meet literature data (measured by methods such as equilibrium dialysis) better than CalcV data do.

Conclusions: There is evidence that Calc2 affords reliable FT and BAT derivation from assayed TT, SHBG, and albumin making direct FT and BAT measurements unnecessary in most cases. Finally, Calc2 was formatted as a preliminary nomogram for convenient clinical use.

Zusammenfassung

Hintergrund: Die auf dem Massenwirkungsgesetz beruhenden Rechenverfahren für freies Testosteron (FT) und „bioverfügbares” Testosteron (BAT) – routinemäßig verwendet zur Erkennung und Beurteilung von Androgenstörungen – stützen sich auf die Annahme, dass das Molekül des sexhormonbindenden Globulins (SHBG) eine einzige steroidbindende Domäne (SBD) enthält. Neuere biochemische Untersuchungen zeigten jedoch, dass dieses Molekül tatsächlich über zwei SBDs verfügt. Dies macht neue Gleichungen (Calc2) für die Berechnung von FT und BAT notwendig.

Methoden und Ergebnisse: Calc2 wurde hergeleitet – zur Anwendung kam die kürzlich publizierte SHBG-Testosteron-Assoziationskonstante – und mit anderen Methoden für FT und/oder BAT verglichen (z. B. mit einer herkömmlichen Rechenvariante [CalcV], mit der Ammoniumsulfat-Präzipitation [zur Messung von BAT], basierend auf mittels Massenspektrometrie bestimmtem Total-Testosteron [TT], und mit einem sich als zufriedenstellend erweisenden Radioimmunoassay [RIA] für FT). Das mit Calc2 ermittelte BAT deckte sich, im Gegensatz zum CalcV-BAT, mit dem mit der Ammoniumsulfat-Präzipitation gefundenen BAT. Einen analogen Befund ergab ein Vergleich von FT-Quotienten, bestimmt mittels RIA, Calc2 bzw. CalcV. Überdies: Den auf Methoden wie der Gleichgewichtsdialyse beruhenden Literaturdaten scheinen die Calc2-Daten größtenteils besser zu entsprechen als die CalcV-Daten.

Schlussfolgerungen: Vieles deutet darauf hin, dass Calc2 es erlaubt, TT, SHBG und Albumin zu messen und daraus FT und BAT zuverlässig herzuleiten, was direkte FT- und BAT-Messungen in den meisten Fällen unnötig macht. Schließlich wurde Calc2 präsentiert als ein leicht handhabbares, für den klinischen Einsatz geeignetes Nomogramm (Vorentwurf).

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Correspondence: Prof. Dr. med. Andreas R. Huber, Center for Laboratory Medicine, Cantonal Hospital Aarau, Tellstraße, 5001 Aarau, Switzerland Tel.: +41-62-838-53-02 Fax: +41-62-838-53-99

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Published Online: 2006-12-12
Published in Print: 2006-12-01

©2006 by Walter de Gruyter Berlin New York

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