Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia.
BACKGROUND
The n-hexane lipido-sterol extract of Serenoa repens (LSESr, Permixon, Pierre Fabre Medicament, Castres, France), a phytotherapeutic agent used in the treatment of benign prostatic hyperplasia (BPH), has a multisite mechanism of action including inhibition of types 1 and 2 5alpha-reductase and competitive binding to androgen receptors in prostatic cells. Here, the response of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF) in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is analyzed.


METHODS
BPH samples were sectioned in periurethral, subcapsular, and intermediate regions: in each region T, DHT, and EGF were determined by radioimmunoassay after purification on celite columns or Sep-pak C18 cartridges.


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 tissue, respectively). In the LSESr-treated group, a statistically significant reduction was observed, mainly in the periurethral region of DHT (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 confirms the capacity of this drug to inhibit in vivo 5alpha-reductase in human pathological prostate. A marked decrease of EGF, associated with DHT reduction, was also observed. These biochemical effects, similar to those obtained with 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 preferential reduction of DHT and EGF content in the periurethral region is involved in the clinical improvement of the obstructive symptoms in BPH during LSESr therapy.
Department of Urology, University of Rome La Sapienza, Italy.
F
F
Di Silverio
S
S
Monti
A
A
Sciarra
P A
PA
Varasano
C
C
Martini
S
S
Lanzara
G
G
D'Eramo
S
S
Di Nicola
V
V
Toscano
D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D042944:Cholestenone 5 alpha-Reductase; D013196:Dihydrotestosterone / Q000097:blood*; D004815:Epidermal Growth Factor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000503:physiopathology; D028024:Serenoa; D013739:Testosterone / Q000097:blood*
D000726:Androgen Antagonists; D010936:Plant Extracts; D013196:Dihydrotestosterone; D013739:Testosterone; D004815:Epidermal Growth Factor; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase; C040972:saw palmetto extract