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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 m(2) [range, 239-448]) than in women (153 liters/24 hr per m(2) [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 5alpha-androstan-3alpha,17beta-diol (3alpha-diol) and 5alpha-androstan-3beta,17beta-diol (3beta-diol) were identified in plasma during dihydrotestosterone and testosterone infusions. The conversion ratio of dihydrotestosterone to 3alpha-diol (C(BB) (DHT-3alpha)) was greater than the conversion ratio to the 3beta-isomer (C(BB) (DTH-3beta)) in all the patients studied. Both C(BB) (DHT-3alpha) and C(BB) (DHT-3beta) 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 3alpha-diol and 3beta-diol.