Journal of Clinical Endocrinology & Metabolism, Vol 63, 297-302, Copyright © 1986 by Endocrine Society

ARTICLES

Serum luteinizing hormone (LH) biological activity in castrated patients with cancer of the prostate receiving a pure antiandrogen and in estrogen-pretreated patients treated with an LH-releasing hormone agonist and antiandrogen

R St. Arnaud, R Lachance, A Dupont and F Labrie

We recently reported almost complete disappearance of serum LH biological activity in previously untreated patients with advanced prostatic cancer receiving combined therapy with a LHRH agonist and a pure antiandrogen. This decrease in LH bioactivity was most likely responsible for the fall of circulating testosterone to castration levels during such treatment. Since patients previously treated with high doses of estrogens or orchiectomy before receiving combined therapy had a less favorable response to the new treatment, we measured serum LH levels by RIA and the mouse interstitial cell bioassay in these 2 groups of patients. Serum samples were obtained from 14 men with advanced prostatic cancer treated from 9-41 months (24 +/- 9 months) with diethylstilbestrol before receiving 500 micrograms/day LHRH agonist ([D-Trp6]LH/RH ethylamide) in combination with 3 daily oral doses of 250 mg pure antiandrogen flutamide and from 21 men castrated for at least 9 months (32 +/- 26 months) before receiving the antiandrogen alone. In previously castrated patients, both bio- and immunoactive LH serum levels were elevated and did not change during at least 3 months of antiandrogen treatment. In estrogen-pretreated men, however, bioactive LH concentrations declined from 1.2 +/- 0.5 (+/- SEM) to 0.04 +/- 0.01 ng/ml after 1 month of combined treatment and remained low thereafter, while serum LH levels, measured by RIA, did not significantly decline (1.4 +/- 0.5 vs. 0.9 +/- 0.1 ng/ml on days--2 and 30, respectively). This decrease in LH biopotency caused the biological to immunological activity ratio to fall from 0.5 +/- 0.2 before the onset of the combined therapy to 0.05 +/- 0.01 after 3 months. Thus, estrogen pretreatment did not prevent the ability of the LHRH agonist-antiandrogen combination to decrease serum LH biological activity. Moreover, the absence of an effect in castrated patients receiving antiandrogen alone indicates that the LHRH agonist, and not flutamide, was responsible for the effects of the combined therapy.