Sex difference in the metabolism of dehydroisoandrosterone sulfate.

The metabolism of a tracer of [3H]dehydroisoandrosterone sulfate ([3H]DHAS) was studied in five normal women and six normal men. Two major sex differences were found. 1) The total urinary recovery of radioactivity was considerably greater in women (73 +/- 5.5% of the dose vs. 51 +/- 3.5; P less than 0.01), principally due to higher excretion of nonglucuronide, nonsulfate conjugates (35 +/- 2.2% of the dose vs. 21 +/- 3.9%; P less than 0.025). This finding is analogous to the sex difference in estradiol metabolism we have reported and is hypothesized to represent diversion of excretion of these conjugates in women from the biliary to the urinary excretion route because of the known lower biliary excretory capacity of women, which is a consequence of their higher estrogen levels. 2) The recovery of androsterone and etiocholanolone was considerably higher in the women (15.4 +/- 1.4% of the dose vs. 10 +/- 1.8%; P less than 0.05). Since conversion of DHAS to etiocholanolone and androsterone in vivo entails prior cleavage of DHAS to DHA, this sex difference in the recovery of androsterone and etiocholanolone is interpreted to mean that DHAS leads to DHA cleavage is considerably greater in women than in men. It is predicted that the plasma DHA to DHAS ratio should be substantially greater in women then in men.