Dehydroepiandrosterone: kinetics of metabolism in normal men and women

The single injection and constant infusion techniques were utilized to study the kinetics of dehydroepiandrosterone (DHEA) metabolism and its peripheral conversion to several other C19-steroids including C19-steroid sulfates. The MCRs (mean +/- SEM) for normal men and normal women were 1866 +/- 144 and 1901 +/- 87 liters/24 h, respectively. The single injection technique yielded values for rate constants (units) and volumes of distribution (1) as follows: K1, 42.6 +/- 7.7 for men and 37.1 +/- 5.0 for women; K2, 64.3 +/- 11.2 for men and 55.5 +/- 5.0 for women; K2, 64.3 +/- 11.2 for men and 55.5 +/- 5.0 for women; V1, 38.5 +/- 6.0 for men and 33.7 +/- 2.5 for women; V2, 30.4 +/- 7.3 for men and 27.5 +/- 9.9 for women. The constant infusion technique yielded values for the conversion ratios for the transformation of DHEA to several products: delta 5-androstene-3 beta, 17 beta-diol to DHEA of 0.10 +/- 0.01 for men and 0.16 +/- 0.03 for women, delta 4-androstenedione to DHEA of 0.04 +/- 0.01 for men and 0.07 +/- 0.02 for women, DHEA sulfate (DHEAS) to DHEA of 6.36 +/- 0.81 for men and 10.09 +/- 0.87 for women, delta 5-androstene-3 beta, 17 beta-diol sulfate to DHEA of 0.42 +/- 0.06 for men and 0.50 +/- 0.04 for women, and androsterone sulfate to DHEA of 1.11 +/- 0.13 for men and 2.06 +/- 0.18 for women. The ratios for the conversion to DHEA sulfate and androsterone sulfate were significantly higher for women than men. The plasma concentrations of DHEA were 8.50 +/- 0.95 and 8.75 +/- 1.01 ng/ml for men and women, respectively. The calculated production rates for DHEA were 16.34 +/- 2.66 and 16.19 +/- 1.78 mg/24 h for men and women, respectively. There was no sex difference in the binding of DHEA to plasma proteins and this is reflected in the lack of sex difference in the MCRs. Calculations indicate that DHEA is a major precursor of circulating delta 5-diol.