Effect of MK-906, a specific 5 alpha-reductase inhibitor, on serum androgens and androgen conjugates in normal men.
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.
Rittmaster
R S
RS
Department of Medicine, Dalhousie University, Halifax, Nova Scotia.
Stoner
E
E
Thompson
D L
DL
Nance
D
D
Lasseter
K C
KC
D058891:5-alpha Reductase Inhibitors; D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000097:blood*; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000097:blood; D000736:Androstenes / Q000494:pharmacology*; D000738:Androsterone / Q000031:analogs & derivatives / Q000097:blood; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D018120:Finasteride; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism; D051381:Rats; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D000728:Androgens; D000736:Androstenes; D001378:Azasteroids; D013260:Steroids, Heterocyclic; D013196:Dihydrotestosterone; C027927:androsterone glucuronide; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D013739:Testosterone; D018120:Finasteride; D000738:Androsterone; D014453:Glucuronosyltransferase