Selective inhibition of androstenedione‐induced prostate growth in intact beagle dogs by a combined treatment with the antiandrogen cyproterone acetate and the aromatase inhibitor 1‐methyl‐androsta‐1,4‐diene‐3,17‐dione (1‐methyl‐ADD)

Abstract

Interference with estrogenic and androgenic actions might result in an inhibitory effect of benign prostatic hyperplasia (BPH). In the present study the effects of the treatment of intact, adult beagle dogs with the antiandrogen cyproterone acetate (CPA) and the aromatase inhibitor 1-methyl-ADD either alone or in combination on androstenedione-induced prostate growth and on testes, epididymides, and the pituitary was investigated. 1-Methyl-ADD induced a marked counterregulatory increase in the serum testosterone and dihydrotestosterone (DHT) concentrations leading to hyperplasia of the glandular part of the prostate. However, the aromatase inhibitor antagonized the androstenedione-induced (estrogen-related) stimulation of the fibromuscular stroma of the prostate. CPA caused a complete atrophy of the prostate that was also present after treatment with both the aromatase inhibitor and CPA in spite of a striking elevation of the serum testosterone and DHT levels and in spite of the antagonization of the inhibition of testes and epididymal weight induced by androstenedione plus CPA. This indicates a selective inhibition of the prostate of intact beagle dogs treated with CPA and 1-methyl-ADD.

Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats

“…Unlike similar effects in this model with the steroidal AI exemestane, our previous study [30] showed these bone preserving effects are not blocked by the androgen receptor blocker flutamide [33] and thus appear to be non-androgenic [4,30,34,35]. The mechanism of bone preserving effects of ATA remains unexplained.…”

Effects of a new steroidal aromatase inhibitor, TZA-2237, and/or chlormadinone acetate on hormone-induced and spontaneous canine benign prostatic hyperplasia

“…Administration of a 5a-reductase inhibitor, ®nasteride, and an aromatase inhibitor, arimidex, resulted in a signi®cant increase in prostate volume, accompanied by a 3-to 10-fold increase in serum testosterone levels and a signi®cant increase in testicular volume. In connection with the synergistic effects of Atamestane and antiandrogen cyproterone acetate (CPA), it would appear that CPA in combination with Atamestane induced a selective and complete inhibition of the androgenic effects at the level of the prostate, while CPA did not negatively in¯uence the function of the testis, the epididymidis or the pituitary (45). These experimental ®ndings demonstrated that estrogen deprivation with antiandrogen might represent a useful treatment for human BPH.…”

The effects of atamestane and toremifene alone and in combination compared with letrozole on bone, serum lipids and the uterus in an ovariectomized rat model

“…ATA significantly increased BMD, bone mechanical strength and trabecular bone volume in OVX rats. But these bone preserving effects are not blocked by the androgen receptor blocker flutamide (FLT) [38] and thus appear to be non-androgenic [2,39,40]. ATA had no stimulatory effect on the uterine epithelium in OVX rats indicating an absence of an intrinsic estrogenic signal.…”