Estradiol and high-dose dihydrotestosterone treatment causes changes in cynomolgus monkey prostate volume and histology identical to those caused by testosterone alone

Citation
A. Kamischke et al., Estradiol and high-dose dihydrotestosterone treatment causes changes in cynomolgus monkey prostate volume and histology identical to those caused by testosterone alone, J ANDROLOGY, 20(5), 1999, pp. 601-610
Citations number
30
Categorie Soggetti
da verificare
Journal title
JOURNAL OF ANDROLOGY
ISSN journal
01963635 → ACNP
Volume
20
Issue
5
Year of publication
1999
Pages
601 - 610
Database
ISI
SICI code
0196-3635(199909/10)20:5<601:EAHDTC>2.0.ZU;2-D
Abstract
To evaluate the effects of testosterone (T), dihydrotestosterone (DHT), and estradiol (E-2) on the regulation of prostate growth and tissue compositio n, the following study was conducted in a nonhuman primate model. Fifteen a dult, long-term castrated cynomolgus monkeys were randomly assigned to rece ive implants filled with T (0.19 +/- 0.01 g), DHT alone (0.21 +/- 0.01 g), or (99%) DHT + (1%) E-2 (0.21 +/- 0.01 g). Prior to and at 4-week intervals during the treatment phase of 252 days, prostate volumes (PV), body weight , ejaculate weight, hormone levels (of T, DHT, and E-2), and red blood cell count were measured. Five adult, intact monkeys served as controls for pro state volume and histology. At the end of the study, histological analysis of an ultrasound-guided prostate biopsy was performed. T levels increased s ignificantly in the T group compared with baseline (P < 0.01) and with the DHT and DHT + E-2 groups (P < 0.05). Both groups receiving DHT showed highe r DHT levels than did animals in the T group (P < 0.001). E-2 levels in all groups increased over time (P < 0.05), although significant differences (P < 0.01) could only be detected between the DHT + E-2, and the DHT group. P rostate volume in all groups increased (at baseline: T = 1.03 +/- 0.12 ml, DHT = 1.08 +/- 0.15 ml, DHT + E-2 = 1.13 +/- 0.09; at day 252. T = 5.83 +/- 1.00, DHT = 4.72 +/- 0.9, DHT + E-2 = 5.05 +/- 0.62) over time (P < 0.001) , whereas no differences could be detected between the groups. Prostate bio psy could be performed successfully in 15 out of 20 monkeys. Prostate tissu e evaluation between the treatment groups and the evaluated intact monkeys revealed no differences in the status of secretory epithelia, nuclear chrom atin, excretory vacuoles, interstitial stroma, smooth muscles, and total fu nctional status, whereas the prostate of a long-term castrated monkey showe d severe atrophy. Thus, both androgens fully restored prostate volume and e jaculatory function. Highly supraphysiological DHT serum levels are not ass ociated with abnormal volumetric or histological changes of the prostate. C omparing the DHT group with the DHT + E-2 group, an additional stimulatory effect of normal or slightly elevated estrogens on the prostate cannot be f ound in the presence of highly supraphysiological DHT levels.