EFFECTS OF LONG-TERM TREATMENT WITH SERENOA-REPENS (PERMIXON(R)) ON THE CONCENTRATIONS AND REGIONAL DISTRIBUTION OF ANDROGENS AND EPIDERMALGROWTH-FACTOR IN BENIGN PROSTATIC HYPERPLASIA

BACKGROUND. The n-hexane lipido-sterol extract of Serenoa repens (LSES r, Permixon(R), Pierre Fabre Medicament, Castres, France), a phytother apeutic agent used in the treatment of benign prostatic hyperplasia (B PH), has a multisite mechanism of action including inhibition of types 1 and 2 5 alpha-reductase and competitive binding to androgen recepto rs in prostatic cells. Here, the response of testosterone (T), dihydro testosterone (DHT), and epidermal growth factor (EGF) in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is analyzed. ME THODS. BPH samples were sectioned in periurethral, subcapsular, and in termediate regions: In each region T, DHT, and EGF were determined by radioimmunoassay after purification on celite columns or Sep-pak C18 c artridges. RESULTS. In the untreated group, T, DHT, and EGF presented the highest concentrations in the periurethral region (615 +/- 62 (SE) pg/g tissue, 7,317 +/- 551 pg/g tissue, and 20.9 +/- 3.3 ng/g tissue, respectively) with respect to the peripheral subcapsular region (425 +/- 45 pg/g tissue, 4,215 +/- 561 pg/g tissue, and 10.8 +/- 1.4 ng/g t issue, respectively). In the LSESr-treated group, a statistically sign ificant reduction was observed, mainly in the periurethral region of D HT (2,363 +/- 553 pg/g tissue, P < 0.001) and EGF (6.98 +/- 2.48 ng/g tissue, P < 0.01), with increased T values (1,023 +/- 101 pg/g tissue, P < 0.001). CONCLUSIONS. The decrease of DHT and the rise of T in BPH tissue of patients treated with Permixon(R) confirms the capacity; of this drug to inhibit in vivo 5 alpha-reductase in human pathological prostate. A marked decrease of EGF, associated with DHT reduction, was also observed. These biochemical effects, similar to those obtained w ith finasteride, are particularly evident in the periurethral region, whose enlargement is responsible for urinary obstruction, with respect to the subcapsular region. A possible speculation is that the prefere ntial reduction of DHT and EGF content in the periurethral region is i nvolved in the clinical improvement of the obstructive symptoms in BPH during LSESr therapy. (C) 1998 Wiley-Liss, Inc.