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Determination of Bioavailable Testosterone [Non–Sex Hormone–Binding Globulin (SHBG)-Bound Testosterone] in a Population of Healthy French Men: Influence of Androstenediol on Testosterone Binding to SHBG

¹ Assistance Publique-Hôpitaux de Paris (AP-HP), Biological Center of Investigations, University Hospital Group, Sud Henri Mondor, Faculté de Médecine, Créteil, France.
² Institut National de la Santé et de la Recherche Médicale Unité 841 Eq07, Centre Hospitalier Universitaire Henri Mondor, Faculté de Médecine, Créteil, France.
³ Unité de Recherche Clinique Paris Centre, Hôpital Tarnier, Paris, France.
⁴ Institut Inter-Régional pour la Santé, La Riche, France.
⁵ AP-HP, Laboratoire d’Hormonologie, Hôpital St. Antoine, Paris, France.
⁶ AP-HP, Laboratoire de Biochimie, Hôpital Lariboisière, Paris, France.
⁷ Institut Universitaire de Technologie de Cachan, Cachan, France.
⁸ Université Paris VI, Pierre et Marie Curie, Paris, France.

^aAddress correspondence to this author at: Centre de Recherches Chirurgicales, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil Cedex, France. Fax 33-1-49-81-35-52; e-mail giton{at}univ-paris12.fr.

Background: Bioavailable testosterone (BT) is measured [assayed BT (aBT)] or calculated (cBT) in the diagnosis of hypogonadism in men. The cBT depends, however, on the values of the association constants of total testosterone (TT) for sex hormone–binding globulin (SHBG; K_s) and albumin (K_a), and its use therefore remains controversial.

Methods: In 503 selected, untreated healthy men, 20–74 years old, we measured TT, dihydrotestosterone (DHT), and androstenediol (5-diol) by GC-MS, SHBG by RIA, and BT after ammonium sulfate precipitation or by calculation according to the law of mass action.

Results: A slight decrease in TT, significant decreases in BT and 5-diol, no variation in DHT, and an increase in SHBG were observed with age. In young males (39 years), the lower normal limits were between 2.30 and 2.72 nmol/L for aBT and 8.50 nmol/L for TT. For K_s = 1 x 10⁹ L/mol and K_a = 3.6 x 10⁴ L/mol, the lower cBT limit was found to be 2-fold higher than for aBT. With optimized K_s = 1.9 x 10⁹ L/mol and K_a = 2.45 x 10⁴ L/mol, cBT values close to aBT were obtained. When 5-diol was included in the model as a competitive SHBG inhibitor, the correlation between cBT and aBT was better and the cBT:aBT ratios vs 5-diol were less biased.

Conclusion: Lower normal serum aBT concentration in normal men appears to be between 2.30 and 2.72 nmol/L. Much higher serum cBT concentrations are associated with use of different association constants that may be inappropriate. When using the optimized binding constants, taking age-related 5-diol values into consideration slightly improves prediction of cBT.