A pure antiandrogen does not interfere with the LHRH agonist-induced blockade of testicular androgen secretion in the dog.
Daily subcutaneous administration of 50 micrograms of the luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6]LHRH ethylamide in adult dogs causes a transient increase in the serum testosterone (T) concentration which reaches a maximum at 200% above control on days 2-4 of treatment and progressively decreases to 7% of the pretreatment value on day 21, the last time interval studied. After a transient increase, the concentration of serum bioactive luteinizing hormone (LH) was progressively decreased on days 11 and 19, thus suggesting that in analogy with human findings, the loss of LH bioactivity is responsible for the inhibition of testicular steroidogenesis induced in the dog by LHRH agonists. Of major significance is the finding that the changes in serum T levels observed during the first 3 weeks of treatment, as well as the complete inhibition of the intratesticular concentration of sex steroids observed at the end of this period of treatment with the LHRH agonist were not affected by simultaneous administration of flutamide (125 mg per os every 8 h). Such findings indicate that at the dose used, the LHRH agonist is in full control of gonadotropin secretion, thus completely overcoming feedback influences. Since the administration of the antiandrogen flutamide does not decrease the efficacy of the LHRH agonist as blocker of testicular androgen biosynthesis, the present data support the use of a pure antiandrogen in order to neutralize the effect of the transient rise in testicular androgen secretion which always accompanies the first days of treatment with LHRH agonists in patients with advanced prostate cancer.
Lacoste
D
D
Medical Research Council Group in Molecular Endocrinology, Laval University Medical Center, Quebec, Que., Canada.
St-Arnaud
R
R
Bélanger
A
A
Labrie
F
F
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D003692:Delayed-Action Preparations / Q000494:pharmacology*; D004285:Dogs; D005485:Flutamide / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000813:Anilides; D003692:Delayed-Action Preparations; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005485:Flutamide; D007986:Luteinizing Hormone