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Testosterone Metabolic Clearance and Production Rates Determined by Stable Isotope Dilution/Tandem Mass Spectrometry in Normal Men: Influence of Ethnicity and Age

Division of Endocrinology, Department of Medicine (C.W., A.L., G.L., L.H., R.S.S.), Harbor-University of California Los Angeles (UCLA) Medical Center and Research and Education Institute, Torrance, California 90509; and Olympic Analytical Laboratory, Department of Molecular and Medical Pharmacology (D.H.C., B.S., E.D.), UCLA, Los Angeles, California 90025

Address all correspondence and requests for reprints to: Christina Wang, M.D., General Clinical Research Center, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, California 90509. E-mail: wang{at}gcrc.rei.edu.

The metabolic clearance rate (MCR_T) and production rate (PR_T) of testosterone (T) were measured using constant infusion of trideuterated (d₃) T and quantitating serum d₃T by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Serum unlabeled T (d₀T) was measured by LC-MS-MS, and serum total T (d₃T + d₀T) was measured by RIA. Mean MCR_T (measured by LC-MS-MS) in young white men (1272 ± 168 liters/d) was not significantly different from young Asian men (1070 ± 166 liters/d). Mean PR_T was also not significantly different between the two ethnic groups (whites, 9.11 ± 1.11 mg/d; Asians, 7.22 ± 1.15 mg/d; P = 0.19 using d₀T data). Both the mean MCR_T (812 ± 64 liters/d; P < 0.01) and the PR_T (3.88 ± 0.27 mg/d; P < 0.001) were significantly lower in middle-aged white men when compared with their younger counterparts. The mean MCR_T and PR_T calculated using serum total T or d₀T data showed a diurnal variation, with levels at midday significantly higher than those measured in the evening in the young (MCR_T, P < 0.01; PR_T, P < 0.001) and to a lesser extent in the older men (MCR_T, P < 0.05; PR_T, P < 0.05 using total T and P < 0.001 using d₀T data). We conclude that using LC-MS-MS to detect d₃T in serum after constant infusion of stable isotope-labeled T allows the measurements of MCR_T and PR_T, which can be used to study androgen metabolism repeatedly after physiological or pharmacological interventions.

This work was supported by National Institutes of Health Grants RO1 CA-71053 and RO1 DK-61006 (to C.W., D.H.C., and R.S.S.); M01 RR00425 to the General Clinical Research Center at Harbor-UCLA Medical Center; and by the United States Anti-Doping Agency and the National Collegiate Athletic Association (to D.H.C.).

Abbreviations: CV, Coefficient of variation; d₀T, unlabeled T; d₃, trideuterated; GC, gas chromatography; LC, liquid chromatography; LC-MS-MS, LC-tandem MS; MCR, metabolic clearance rate; MCR_T, metabolic clearance rate of T; MS, mass spectrometry; PR, production rate; PR_T, production rate of T; T, testosterone.

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