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 contribution to the formation of 3 alpha-diol G. Design: Prospective study in various 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 men. Interventions: All subjects received IV dihydrotestosterone (DHT) infusions as well as percutaneous administration of DHT. Serum was obtained at multiple time points before and after each administration of DHT. Main Outcome Measures: Comparison of serum levels of DHT, 3 alpha-androstanediol (3 alpha-diol), 3 alpha-diol G, and androsterone glucuronide in the three groups. Results: Steady-state levels of DHT were similar in the three groups and were also similar after the two different routes of administration. However, ratios of 3 alpha-diol G to DHT were significantly greater after percutaneous gel than after IV administration in all three groups. This also was the case for the ratio of unconjugated serum 3 alpha-diol to DHT. Levels of androsterone glucuronide were similar with the different routes of administration. Conclusion: Using nonoral routes of administration and, in attempting to assess in vivo metabolism of DHT, our data confirm that the skin is the major site of unconjugated 3 alpha-diol and 3 alpha-diol G formation. Serum 3 alpha-diol G, therefore, appears largely to reflect skin DHT metabolism.