Serum levels of LH, FSH and testosterone (T) were measured by radioimmunoassays in 36 patients with advanced prostate cancer before and during androgen ablation therapies. Both leuprolide acetate (LH-RH agonist: LHRH-A) and diethylstilbestrol diphosphate (DES-DP) administration decreased serum LH significantly to an undetectable level (LHRH-A: P < 0.01, DES-DP: P < 0.05). LHRH-A and DES-DP diminished serum FSH to 20% of the pre-treatment level (P < 0.005) and to an undetectable level (P < 0.001), respectively. LHRH-A and DES-DP decreased serum T to the castration level and an undetectable level, respectively (P < 0.001). Serum levels of the same 3 hormones before and after DES-DP administration were measured in 8 patients who received DES-DP after LHRH-A treatment or castration because of relapse of the disease. DES-DP lowered serum FSH further than LHRH-A to an undetectable level (P < 0.005) and diminished T further than previous treatments to an undetectable level (P < 0.05 vs. LHRH-A, P < 0.01 vs. castration). These results suggest that 1) DES-DP is able to reduce T production from extra-testicular site(s), and achieve the minimal serum T level, and 2) this DES-DP action appears to be one of the mechanisms of the effectiveness of the estrogen on refractory prostate cancer after castration or LHRH-A. In addition, basal (independent of LH-RH) FSH secretion in elderly men is about 20% of total FSH secretion and DES-DP inhibits the basal FSH secretion at the level of the pituitary.
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