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

The metabolic clearance rate (MCRT) and production rate (PRT) 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 MCRT (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 PRT 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 MCRT (812 ± 64 liters/d; P < 0.01) and the PRT (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 MCRT and PRT 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 (MCRT, P < 0.01; PRT, P < 0.001) and to a lesser extent in the older men (MCRT, P < 0.05; PRT, 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 MCRT and PRT, which can be used to study androgen metabolism repeatedly after physiological or pharmacological interventions.