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Journal of Andrology, Vol 10, Issue 4 259-262, Copyright © 1989 by The American Society of Andrology

JOURNAL ARTICLE

Effect of MK-906, a specific 5 alpha-reductase inhibitor, on serum androgens and androgen conjugates in normal men

R. S. Rittmaster, E. Stoner, D. L. Thompson, D. Nance and K. C. Lasseter
Department of Medicine, Dalhousie University, Halifax, Nova Scotia.

To determine the hormonal effects of MK-906, an orally active 5 alpha-reductase inhibitor, on serum androgens and androgen conjugates, 12 healthy men were given 10, 20, 50, and 100 mg MK-906 2 weeks apart in randomized order in a 4-period crossover design. Serum testosterone (T), dihydrotestosterone (DHT), androstanediol glucuronide, and androsterone glucuronide were measured before and 24 hours after each dose. The effect of MK-906 on glucuronyl transferase activity, the enzyme responsible for androstanediol glucuronide and androsterone glucuronide formation, was assessed in vitro using rat prostate tissue. Serum T levels were unchanged after all doses. Serum DHT, androstanediol glucuronide, and androsterone glucuronide were suppressed by 70, 40, and 56%, respectively, after the 10-mg dose, and by 82, 52, and 66% after the 100-mg dose (P less than 0.02 for the comparison between the 10 and 100-mg doses for all three steroids), respectively. Baseline serum T and DHT levels were strongly correlated (R = 0.89, P = 0.0002), as were androstanediol glucuronide and androsterone glucuronide levels (R = 0.78, P = 0.003), but there was no correlation between DHT levels and the levels of either conjugated steroid. MK-906 had no effect on glucuronyl transferase activity in vitro. It was concluded that single doses of MK-906 suppress both conjugated and unconjugated 5 alpha-reduced androgens. While all three steroids appeared to be good markers of systemic 5 alpha-reductase inhibition, further research will be needed to determine which steroid best reflects tissue DHT levels in patients receiving these inhibitors.


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