A luteinizing hormone-releasing hormone (LH-RH) analogue was administered for 3 to 32 months to 15 prostatic cancer patients in stage B-D (B:3, C:8, D:4).
Intratesticular, intratubular and prostatic androgen levels were measured by radioimmunoassay before and after LH-RH analogue therapy. The measurement of serum prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) levels was also conducted. Thereafter, we assessed the effect of the LH-RH analogue on androgen levels and the relation of prostatic tissue 5α-dihydrotestosterone (DHT) level to the clinical response.
The results were as follows:
1) Johnsen's mean germinal epithelium count was significantly decreased from 7.7±2.1 (mean±S.D.) to 4.3±2.3, and the wall thickness of seminiferous tubules was increased from 5.93±1.31 to 11.9±3.64μm.
2) Plasma testosterone (T), intratesticular and intratubular androgen levels were significantly decreased (plasma T: from 4.40±1.84 to 0.61±0.32ng/ml, intratesticular T: from 335.3±170.3 to 4.6±3.8ng/g.t.w., DHT: from 25.3±11.7 to 3.7±2.7ng/g.t.w., intratubular T: from 50.8±36.6 to 0.10±0.99ng/g.t.w. and DHT: 7.54±3.20 to 0.63±0.90ng/g.t.w.).
3) Crude nuclear DHT levels in prostatic tissue fell from 15.3±9.3 (N=8) to 0.37±0.54pg/mg protein (N=3) and the level was non-detectable in 5 of 8 cases.
4) Complete remission was achieved in 1 patient, partial response in 5, objective stable in 8, and objective progression in 1 patient, according to Shimazaki's criteria.
Moreove, the clinical response in patients with high pretreatment prostatic tissue DHT levels (over 10pg/mg protein or 2ng/g.t.w.) is good to LH-RH analogue therapy.
Therefore, the LH-RH analogue seems to have a strong inhibitory effect on both intratesticular and intratubular androgen levels and appears to be an appropriate agent for treating prostatic cancer patients with high prostatic tissue DHT levels.
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