Estradiol and High‐Dose Dihydrotestosterone Treatment Causes Changes in Cynomolgus Monkey Prostate Volume and Histology Identical to Those Caused by Testosterone Alone

Abstract

ABSTRACT: To evaluate the effects of testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) on the regulation of prostate growth and tissue composition, the following study was conducted in a nonhuman primate model. Fifteen adult, long‐term castrated cynomolgus monkeys were randomly assigned to receive implants filled with T (0.19 ± 0.01 g), DHT alone (0.21 ± 0.01 g), or (99%) DHT + (1%) E2 (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 E2), and red blood cell count were measured. Five adult, intact monkeys served as controls for prostate volume and histology. At the end of the study, histological analysis of an ultrasound‐guided prostate biopsy was performed. T levels increased significantly in the T group compared with baseline (P < 0.01) and with the DHT and DHT + E2 groups (P < 0.05). Both groups receiving DHT showed higher DHT levels than did animals in the T group (P 0.001). E2 levels in all groups increased over time (P < 0.05), although significant differences (P < 0.01) could only be detected between the DHT + E2 and the DHT group. Prostate volume in all groups increased (at baseline: T = 1.03 ± 0.12 ml, DHT = 1.08 ± 0.15 ml, DHT + E2 = 1.13 ± 0.09; at day 252: T = 5.83 ± 1.00, DHT = 4.72 ± 0.9, DHT + E2 = 5.05 ± 0.62) over time (P < 0.001), whereas no differences could be detected between the groups. Prostate biopsy could be performed successfully in 15 out of 20 monkeys. Prostate tissue evaluation between the treatment groups and the evaluated intact monkeys revealed no differences in the status of secretory epithelia, nuclear chromatin, excretory vacuoles, interstitial stroma, smooth muscles, and total functional status, whereas the prostate of a long‐term castrated monkey showed severe atrophy. Thus, both androgens fully restored prostate volume and ejaculatory function. Highly supraphysiological DHT serum levels are not associated with abnormal volumetric or histological changes of the prostate. Comparing the DHT group with the DHT + E2 group, an additional stimulatory effect of normal or slightly elevated estrogens on the prostate cannot be found in the presence of highly supraphysiological DHT levels.