The metabolic clearance rate and origin of plasma dihydrotestosterone in man and its conversion to the 5α-androstanediols

Abstract

Dihydrotestosterone metabolism was studied with a constant infusion technique in three men, three women, five hirsute women, and four estrogen-treated hirsute women. The mean dihydrotestosterone metabolic clearance rate was higher in men (336 liters/24 hr per m² [range, 239-448]) than in women (153 liters/24 hr per m² [range, 108-184]). The metabolic clearance rates in hirsute patients were intermediate between those men and women and were decreased by estrogen treatment. These observations demonstrate similarities in the metabolic rates of testosterone and dihydrotestosterone. The conversion of plasma testosterone and androstenedione to dihydrotestosterone was studied in men and hirsute women. Approximately 4 and 2% of plasma testosterone and androstenedione, respectively, were converted to plasma dihydrotestosterone in both groups. From these observations it was determined that a major fraction of plasma dihydrotestosterone was derived from these plasma precursors rather than from glandular secretion. Both 5α-androstan-3α,17β-diol (3α-diol) and 5α-androstan-3β,17β-diol (3β-diol) were identified in plasma during dihydrotestosterone and testosterone infusions. The conversion ratio of dihydrotestosterone to 3α-diol (C_BB^DHT-3α) was greater than the conversion ratio to the 3β-isomer (C_BB^DTH-3β) in all the patients studied. Both C_BB^DHT-3α and C_BB^DHT-3β were higher in men (mean values of 0.151 [range, 0.110-0.222] and 0..031 [range, 0.022-0.042]) than in women (means of 0.044 [range, 0.037-0.048] and 0.012 [range 0.010-0.013]). A smaller fraction of testosterone was converted to 3α-diol and 3β-diol.