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Three-Month Treatment With a Long-Acting Gonadotropin-Releasing Hormone Agonist of Patients With Benign Prostatic Hyperplasia: Effects on Tissue Androgen Concentration, 5-Reductase Activity and Androgen Receptor Content^*

GIANNI FORTI, ROBERTO SALERNO, GLORIANO MONETI, SONIA ZOPPI, GIANNA FIORELLI, TARCISIO MARINONI, ALESSANDRO NATALI, ALFIERO COSTANTINI, MARIO SERIO, LUCIANO MARTINI and MARCELLA MOTTA

Endocrinology Unit, Department of Clinical Physiopathology, (G.Fo., G.Fi), Department of Urology, (A.N., A.C.), and Department of Pharmacology (G.M.), University of Florence Florence, Italy
the Institute of Endocrinology, University of Milan (S.Z., T.M., L.M., M.M.) Milan, Italy

Address all correspondence and requests for reprints to: G. Forti, M.D., Endocrinology Unit, Department of Clinical Physiopathology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.

The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men. We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5-androstan-3,17β-diol (3-diol); 2) prostatic 5-reductase activity; and 3) the prostatic content of androgen receptors (AR). Plasma T, DHT, and 3-diol levels also were measured. Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied. The mean DHT and 3-diol concentrations in the prostatic tissue of the treated men were about 10/ of those in untreated men (n = 19; P < 0.01 for DHT and P < 0.05 for 3-diol), and the mean intraprostatic T concentration in the treated men was about 25/ of that in the control group (0.10 > P > 0.05). The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50/ lower (P < 0.05) than that by prostatic tissue of the untreated men (n = 9). The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P < 0.05), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P < 0.05) than that in the prostatic tissue of the untreated men (n = 8). The mean plasma T levels in treated men decreased from 4.77 ± 1.79 (SD) ng/mL (16.5 ± 6.2 nmol/L) to 0.27 ± 0.42 ng/mL (0.9 ± 1.5 nmol/L) after 1 month of therapy and remained in the castrate range thereafter.

We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3-diol to about one tenth of the levels in untreated men. Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients. The decrease in prostatic 5a-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations.

^* This work was supported by the CNR through the Special Projects Oncology (contracts 86.00415.44 and 87.01343.44) and Preventive and Rehabilitative Medicine (contract 87.00373.56), a grant from the Associazione Italians per la Ricerca sul Cancro, and a Grant from the University of Florence.

Fellow of the Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.

Received April 12, 1988.

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