Dehydroepiandrosterone metabolism in the female rhesus monkey: oral versus intravenous administration

Because of the biologic effects on a variety of end points reported for dehydroepiandrosterone (DHA) and its sulfate (DHAS) after oral administration, we studied the metabolism of DHA in six female rhesus monkeys after oral and after intravenous administration. We administered [4-14C]DHA p.o. and [7-3H]DHA i.v. simultaneously, drawing blood samples at increasingly longer intervals for 24 h. The mean +/- SE metabolic clearance rate of the intravenous DHA was 404 +/- 49 L/day. The mean metabolic clearance rate was 2,601 +/- 261 L/day after oral administration, and the calculated absorption was 16.3 +/- 2.5%. There was rapid conversion of p.o. DHA to DHAS, as the conversion ratio of the orally administered DHA measured in the blood as [4-14C]DHAS was 63.3 +/- 13.6, whereas the conversion ratio of intravenously administered DHA to DHAS was 9.3 +/- 2.0. Small amounts of DHA were measured in the blood as testosterone and androstenedione after both forms of administration. We conclude that there is marked metabolism in splanchnic tissue of orally administered DHA to DHAS prior to its entry into the bloodstream, and the absorption of DHA itself is minimal when administered by mouth to the rhesus monkey.