Inhibition of basal and adrenocorticotropin-stimulated plasma levels of adrenal androgens after treatment with an antiandrogen in castrated patients with prostatic cancer.
The basal plasma levels of cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and testosterone were studied in 20 patients with advanced prostatic cancer receiving combined treatment with an LHRH agonist and an antiandrogen [5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)-phenyl]-2 4-imidazolidinedione]. After 60 days of combined antihormonal therapy, plasma levels of testosterone decreased from 5.44 +/- 0.44 (SEM) to 0.136 +/- 0.052 ng/ml (2.5% of control). Somewhat unexpectedly, the plasma concentrations of the adrenal androgens DHEA and DHEA-S were reduced to 45 +/- 7 and 64 +/- 4% of control, respectively. The maximal reduction in plasma adrenal androgen levels occurred between 2 and 4 weeks of treatment. Whereas the increase in serum cortisol, 17-hydroxypregnenolone, and 17-hydroxyprogesterone concentrations 2 1/2 h after the injection of 0.25 mg human ACTH 1-24 was not affected by the combined treatment, the increment of DHEA and androstenedione after the same stimulus was reduced from 3.1 +/- 0.98 and 0.73 +/- 0.11 to 1.48 +/- 0.5 and 0.31 +/- 0.05 ng/ml, respectively. The reduced levels of serum DHEA and DHEA-S were not due to the LHRH agonist by itself, since similarly low levels of serum DHEA and DHEA-S were found in patients surgically castrated and receiving the same antiandrogen. These data suggest that treatment with an antiandrogen in castrated men inhibit the formation of adrenal androgens due to a blockade at the level of 17, 20-desmolase. The efficiency of the new combined antihormonal therapy (castration and antiandrogen) aimed at complete androgen neutralization in prostate cancer is thus further facilitated.
D000324:Adrenocorticotropic Hormone; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000097:blood*; D002064:Buserelin / Q000627:therapeutic use*; D002369:Castration; D003131:Combined Modality Therapy; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D000728:Androgens; D007093:Imidazoles; D048289:Imidazolidines; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D003687:Dehydroepiandrosterone; C021277:nilutamide; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D002064:Buserelin; D006854:Hydrocortisone