The Production, Origin and Role of Dehydroepiandrosterone and Δ5-Androstenediol as Androgen Prehormones in Hirsute Women1

Abstract
Blood production rates (PB) of dehydroepiandrosterone (DHEA) and Δ5-androstenediol (Δ5-diol) were measured in a group of 22 women with hirsutism. The PBDHEA averaged 14.9 mg/day (2½ times normal), and was reflected by differences in plasma DHEA concentrations, when compared with normal women. PBΔ5-diol in the hirsute women averaged 1.27 mg/day and was also 2½-fold elevated; however, since the metabolic clearance rates of Δ5-diol were 2-fold elevated, the plasma Δ5-diol levels in the hirsute group were only slightly high when compared with normal women. The peripheral metabolism of DHEA was investigated by determining its blood transfer constants (ρ) to Δ5-diol, androstenedione (Δ4-dione) and testosterone (T). Circulating DHEA accounted for 1/3 of the total Δ5-diol produced in normal women, and for ½ of the Δ5-diol produced in the hirsute group. DHEA accounted for 6–7% of Δ4-dione in both normal and hirsute women. The ρBBDHEA→T averaged 0.4% in normal women and 0.6% in hirsute women, thus accounting for only 82 μg/day or 8% of the total testosterone production in the latter group. Androstenediol metabolism was similiarly examined by measuring its ρ constants to DHEA, Δ4-dione and T. The ρBBΔ5-dilol→T was 0.023 in normal women, and 0.011 in hirsute women, accounting for only 12–14 Mg of PBT in both groups. Thus, neither DHEA nor Δ5-diol were significant prehormones of testosterone in normal or hirsute women. Adrenal vein catheterizations revealed DHEA concentrations that were 110 times greater than peripheral blood, whereas ovarian venous effluents contained 6-fold gradients of DHEA. Thus, DHEA overproduction in hirsute women was largely adrenal in origin. Androstenediol gradients were noted in ovarian venous samples in 4 of 5 hirsute women.