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