Effects of long-term administration of androgens and estrogen on rhesus monkey prostate: Possible induction of benign prostatic hyperplasia

Rhesus monkeys were used to investigate the role of androgenic steroids and estradiol in the induction of hyperplastic changes in stromal and glandula r prostate tissues. Adult male rhesus monkeys were procured from the wild a nd, after routine quarantine procedures, were randomly divided into 5 group s of 5 animals each. Gluteus maximus muscles were injected with 2.5 mg of a ndrostenedione (Group II), 2.5 mg of dihydrotestosterone (DHT) or 0.25 mg o f estradiol (Group ill), 2.5 mg androstanediol (Diol; Group IV), or Diol in combination with 0.25 mg of estradiol (Group V). Group I consisted of untr eated controls. Animals were injected with steroids 3 times a week for 2 ye ars. Treatment with androstenedione (Group II) resulted in stromal hyperpla sia in the caudal lobe and an increase in epithelial cell height in all zon es except in the central zone of the caudal lobe. In monkeys treated with D HT and estradiol (Group III), stromal hyperplasia in both robes, a decrease in tubular size, and degranulation and vacuolation of epithelial cells wer e noticed. Injection of Diol alone (Group IV) or in combination with estrad iol (Group V) resulted in a widening of stroma in the central and periphera l zones of cranial and caudal lobes, whereas the tubular size de-creased. D iol also induced epithelial cell hypercellularity in the central and periph eral zones of the caudal lobe and in the peripheral zone of the cranial lob e. Prostate-specific antigen levels in Group IV animals gradually increased from 6 months of treatment and were maximal after 18 months of injections. Serum estradiol levels increased to detectable levels in all groups except Group IV. Serum testosterone levels decreased to very low or undetectable levels in all groups, whereas prostate-specific acid phosphatase increased in all treated groups. Prolactin levels were elevated in all treated groups except in animals injected with androstenedione. These results indicate th at repeated long-term injections of androstenedione or DHT and estradiol in duced stromal hyperplasia, which may be an estrogen-related effect. Androst anediol-induced hypercellularity and stratification of glandular epithelium is comparable to human prostatic intraepithelial neoplasia. These results also suggest that the rhesus monkey is a suitable animal model for experime ntal induction of prostate diseases.