In Vivo 4-androstene-3,17-dione and 4-androstene-3β, 17β-diol Supplementation in Young Men

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To determine if known androgenic hormone precursors for testosterone in the androgen pathway would be readily transformed to testosterone, eight male subjects [mean age 23.8 (SEM 3) years, bodymass 83.1 (SEM 8.7) kg, height 175.6 (SEM 8.5) cm] underwent a randomized, double-blind, cross-over, placebo-controlled oral treatment with 200 mg of 4-androstene-3,17-dione (Δ4), 4-androstene-3β,17β-diol (Δ4Diol), and placebo (PL). The periods of study were separated by 7 days of washout. Blood was drawn at baseline and subsequently every 30 min for 90 min after treatment. Analysis revealed mean area-under-the-curve (AUC) serum Δ4 concentrations to be higher during Δ4 treatment [2177 (SEM 100) nmol.l-1] than Δ4Diol [900 (SEM 96) nmol.l-1] or PL [484 (SEM 82) nmol.l-1; P < 0.0001]. The Δ4 treatment also revealed a significant effect on total testosterone with a mean AUC [1632.5 (SEM 121) nmol.l-1] that was greater than PL [1418.5 (SEM 131) nmol.l-1; P < 0.05] but not significantly different from those observed after Δ4Diol treatment [1602.9 (SEM 119) nmol.l-1; P = 0.77]. Free testosterone concentrations followed a similar pattern where mean AUC for the Δ4 treatment [6114.0 (SEM 600) pmol.l-1] was greater than after PL [4974.6 (SEM 565) pmol.l-1; P < 0.06] but not significantly different from those observed after Δ4Diol [5632.0 (SEM 389) pmol.l-1; P = 0.48]. The appearance and apparent conversion to total and free testosterone over 90 min was stronger for the Δ4 treatment (r = 0.91, P < 0.045) than for Δ4Diol treatment (r = 0.69, NS) and negatively correlated for PL (r = -0.90, P < 0.02). These results would suggest that Δ4, and perhaps Δ4Diol, taken by month are capable of producing in vivo increases in testosterone concentrations in apparently healthy young men as has already been observed in women after treatment with Δ4.