Atamestane is a new, competitive, and irreversible inhibitor of
estrogen biosynthesis. Its
pharmacologic action has been evaluated in mice, rats, rabbits, dogs, monkeys, and humans. In rats,
atamestane leads to a decrease of pregnant mare serum
gonadotropin-stimulated ovarian
estrogen production, and inhibits
androstenedione-induced
estrogenic effects such as uterine growth and abortion. In all species tested,
atamestane lacks other intrinsic hormonal or antihormonal activities, and shows no inhibition of other
cytochrome P450-dependent
enzymes of adrenal steroidogenesis. However, it inhibits
estrogen-related negative feedback. The extent and consequences of the induced counterregulation of the pituitary-hypothalamic axis show major sex- and species-specific differences.
Atamestane is highly effective in inhibiting
estrogen-induced hyperplastic changes in the fibromuscular stroma of the prostate in
androstenedione-treated dogs and monkeys. In male volunteers and patients with
benign prostatic hyperplasia (BPH),
atamestane induces an expected reduction of serum (and BPH tissue)
estrogen concentrations without significant changes in
androgen levels. In conclusion, all available results indicate that
atamestane is a selective (no inhibition of adrenal function), pure (no endocrine side effects), and highly effective steroidal
aromatase inhibitor, with an excellent safety profile. Based on the discussion of its clinical potential,
atamestane seems to be a promising compound for the management of BPH.