Chlormadinone acetate pellet implantation plus short‐term oral administration in dogs with benign prostatic hypertrophy

Abstract

Eight beagles with benign prostatic hypertrophy (BPH) were treated by subcutaneous implantation of pellets containing 10 mg/kg chlormadinone acetate (CMA), a synthetic anti-androgen, plus daily oral administration of CMA at 2 mg/kg per day for 7 days as a therapy for BPH. Prostatic and testicular size were measured and prostatic and testicular biopsies were performed by laparotomy before and after CMA treatment. Plasma levels of luteininzing hormone (LH), testosterone and oestradiol were also measured. The clinical signs of BPH, for example haematuria and dysuria, resolved within 1 week of treatment. Mean prostatic volume decreased to 56% of the pretreatment value. At 40 weeks after treatment, prostatic volume had decreased by 36%. Histological examination of the prostate 1 week after treatment revealed reduction in diameter of the alveoli and in height of the glandular epithelium. Degeneration and atrophy of the glands were marked 4-12 weeks after treatment. In the testis, the diameter of seminiferous tubules and the number of germ cells in the seminiferous tubules had decreased markedly at 12 and 24 weeks after treatment. Although plasma LH concentrations did not undergo any marked fluctuations after CMA treatment, levels of testosterone and oestradiol were lower than before treatment. The results indicate that implantation of 10 mg/kg CMA, plus 7-day oral administration of 2 mg/kg CMA, bring about resolution of the clinical signs and marked reduction in prostatic volume within 1 week of treatment.

Effect of Osaterone Acetate Administration on Prostatic Regression Rate, Peripheral Blood Hormone Levels and Semen Quality in Dogs with Benign Prostatic Hypertrophy.

“…In treatment of BPH, because the prostate is an androgen (A)-dependent organ, orchidectomy [11] or treatment with anti-A agents [1,3] is performed. We previously showed that oral administration of chlormadinone acetate (CMA), which is a commercially available anti-A agent for human use, improved clincial symptoms during the early phase of BPH [4,10]. However, we also reported that the size of the prostate returned to the same size as that prior to administration 12 weeks later [10].…”

Local injection of a sustained‐release antiandrogen formulation into a target prostatic site: an experimental study

“…Daily oral administration of CMA for several weeks caused atrophy of the glandular alveoli in dogs with BPH [22]. The combination of a tablet for internal use and a pellet for s.c. use successfully achieved an early resolution in dogs with BPH [23]. In a rat model, there was a reduction of the capillary luminal area of the prostate, as assessed by transmission electron microscopy, after 5 days of CMA treatment, suggesting that the action of androgens is directly inhibited by CMA at the cellular level, and decreases blood supply to the prostate as a result [24].…”

“…There are limitations to the present study; the size and condition of the prostate are evidently different between normal rats and patients with BPH or prostatic cancer in the clinical setting. Animal experiments on prostate treatment were reported for dogs with spontaneous BPH [21–23], normal rats [24,27], and nude mice [28], using the i.v. [28] and s.c. routes [27,29].…”