Received on February 10, 2007
Accepted on September 18, 2007

Endocrinology and Metabolism

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, and Institut National de la Santé et de la Recherche Médicale Unité 841 Eq07, Centre Hospitalier Universitaire Henri Mondor, Faculté de Médecine, Créteil, France
² Unité de Recherche Clinique Paris Centre, Hôpital Tarnier, Paris, France
³ Institut Interrégional pour la Santé, La Riche, France
⁴ AP-HP, Laboratoire d'Hormonologie, Hôpital St. Antoine, Paris, France
⁵ AP-HP, Laboratoire de Biochimie, Hôpital Lariboisière, Paris, France
⁶ Institut Universitaire de Technologie de Cachan, Cachan, France
⁷ Université Pierre et Marie Curie, Paris, France
⁸ Institut National de la Santé et de la Recherche Médicale Unité 841 Eq07, Centre Hospitalier Universitaire Henri Mondor, Faculté de Médecine, Créteil, France

^* To whom correspondence should be addressed. 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.