METABOLISM OF DIHYDROTESTOSTERONE TO 5-ALPHA-ANDROSTANE-3-ALPHA,17-BETA-DIOL GLUCURONIDE IS GREATER IN THE PERIPHERAL COMPARTMENT THAN IN THE SPLANCHNIC COMPARTMENT

Objective: To compare the peripheral versus the splanchnic contributio n to the formation of 3 alpha-diol G. Design: Prospective study in var ious groups of women and men. Setting: Reproductive Endocrine service of our University Medical Center. Patients: Six normal ovulatory women , five hirsute women with polycystic ovary syndrome, and six normal me n. Interventions: All subjects received IV dihydrotestosterone (DHT) i nfusions as well as percutaneous administration of DHT. Serum was obta ined at multiple time points before and after each administration of D HT. Main Outcome Measures: Comparison of serum levels of DHT, 3 alpha- androstanediol (3 alpha-diol), 3 alpha-diol G, and androsterone glucur onide in the three groups. Results: Steady-state levels of DHT were si milar in the three groups and were also similar after the two differen t routes of administration. However, ratios of 3 alpha-diol G to DHT w ere significantly greater after percutaneous gel than after IV adminis tration in all three groups. This also was the case for the ratio of u nconjugated serum 3 alpha-diol to DHT. Levels of androsterone glucuron ide were similar with the different routes of administration. Conclusi on: Using nonoral routes of administration and, in attempting to asses s in vivo metabolism of DHT, our data confirm that the skin is the maj or site of unconjugated 3 alpha-diol and 3 alpha-diol G formation. Ser um 3 alpha-diol G, therefore, appears largely to reflect skin DHT meta bolism.