Metabolism of orally administered androstenedione in young men

Androstenedione is a steroid hormone and the major precursor to testosteron e. It is available without prescription and taken with the expectation that it will be converted to testosterone endogenously and increase strength an d athletic performance. The metabolism of orally administered testosterone has not been well studied. We randomly assigned 37 healthy men to receive 0, 100, or 300 mg oral andro stenedione in a single daily dose for 7 d. Single 8-h urine collections wer e performed on the day before the start of the androstenedione administrati on and on d I and 7 to assess excretion rates of free and glucuronide-conju gated testosterone, androsterone, etiocholanolone, and dihydrotestosterone. Serum testosterone glucuronide concentrations were measured by frequent bl ood sampling over 8 h on d 1 in 16 subjects (5 each in the 0 and 100 mg gro up and 6 in the 300 mg group). In the control group, mean (+/- SE) d I and 7 excretion rates for testoster one, androsterone, etiocholanolone, and dihydrotestosterone were 3 +/- 1, 2 15 +/- 26, 175 +/- 26, and 0.4 +/- 0.1 mug/h, respectively. In the 100 mg g roup, mean d I and 7 excretion rates for testosterone, androsterone, etioch olanolone, and dihydrotestosterone were 47 +/- 11, 3,836 +/- 458,4,306 +/- 458, and 1.6 +/- 0.2 mug/h, respectively. In the 300 mg group, mean d I and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dih ydrotestosterone were 115 +/- 39, 8,142 +/- 1,362, 10,070 +/- 1,999, and 7. 7 +/- 1.5 mug/h, respectively. Urinary excretion rates of all metabolites w ere greater in both the 100 and 300 mg groups than in controls (P < 0.0001) . Urinary excretion rates of testosterone (P = 0.007), androsterone (P = 0. 009), etiocholanolone (P = 0.0005), and dihydrotestosterone (P < 0.0001) we re greater in the subjects who received 300 mg androstenedione than in thos e who received 100 mg. In the treated groups, excretion of free testosteron e accounted for less than 0.1% of the total excreted testosterone measured. Serum testosterone glucuronide levels increased significantly during frequ ent blood sampling in both the 100 and 300 mg groups compared with controls (P = 0.0005 for the 100 mg group; P < 0.0001 for the 300 mg group). The ne t mean changes in area under the curve for serum testosterone glucuronide w ere - 18 +/- 25%, 579 +/- 572%, and 1267 +/- 1675% in the groups receiving 0, 100, and 300 mg/d androstenedione, respectively. We conclude that the administration of both 100 and 300 mg androstenedione increases the excretion rates of conjugated testosterone, androsterone, eti ocholanolone, and dihydrotestosterone and the serum levels of testosterone glucuronide in men. The magnitude of these increases is much greater than t he changes observed in serum total testosterone concentrations. These findi ngs demonstrate that orally administered androstenedione is largely metabol ized to testosterone glucuronide and other androgen metabolites before rele ase into the general circulation.