Disease relevance of ATAMESTANE

• Placebo controlled double-blind study to test the efficacy of the aromatase inhibitor atamestane in patients with benign prostatic hyperplasia not requiring operation. The Schering 90.062 Study Group [1].

High impact information on ATAMESTANE

• Inhibition experiments with atamestane, an inhibitor of aromatase cytochrome P450, revealed specific, dose-responsive, and competitive inhibition of both brain and placental aromatase activities [2].
• METHODS: Two hundred and ninety-two patients with clinical symptoms of BPH were randomly allocated to one of the following treatments for 48 weeks: placebo or the selective aromatase inhibitor, atamestane, at a daily dose of 100 mg or 300 mg [3].
• CONCLUSIONS: The conclusion from this study is that the reduction in estrogen concentration using the selective aromatase inhibitor atamestane has no effect on clinically established BPH [3].
• Comparison of the effects of the irreversible aromatase inhibitor exemestane with atamestane and MDL 18962 in rats with DMBA-induced mammary tumours [4].
• Anti-androgen effects of the aromatase inhibitor, atamestane [5].

Chemical compound and disease context of ATAMESTANE

• Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia: results of a double-blind, placebo-controlled, randomized clinical trial using two doses of the aromatase-inhibitor atamestane. Atamestane Study Group [3].
• 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 [6].

Biological context of ATAMESTANE

• There seem to be two principal routes by which atamestane is metabolized: one route is characterized by the attack of 17 beta-hydroxysteroid dehydrogenase, the other route includes hydroxylation of the 1-methyl group with subsequent attack by 5 beta-reductase, followed by a hydroxylation at position C-6 [7].

Anatomical context of ATAMESTANE

• This study evaluated the effect of atamestane (a competitive inhibitor of P-450 aromatase) on granulosa luteal cells from polycystic and normal ovaries [8].
• Treatment with atamestane (10 micromol/l) determined a strong inhibition of basal aromatase activity in both types of cells; however, its effect was markedly more pronounced in granulosa cells from normal ovary than in granulosa cells from polycystic ovaries (PCO; P < 0.01) [8].

Associations of ATAMESTANE with other chemical compounds

• In addition, the increase in intraprostatic estrogen concentrations and immunohistochemically detectable estrogen receptor content induced by androstenedione in intact dogs is completely reversed by simultaneous treatment with atamestane [9].
• Female Sprague-Dawley rats bearing DMBA-tumors were treated s.c. once daily either with 30 or 150 mg/kg atamestane or with 0.1 or 0.5 mg/kg CGS 16949A for 4 weeks [10].

Gene context of ATAMESTANE

• These effects can be antagonized by aromatase inhibitors, such as atamestane [9].
• Atamestane: an aromatase inhibitor for the treatment of benign prostatic hyperplasia. A short review [11].
• In all species tested so far, atamestane lacks other intrinsic hormonal or antihormonal activities and shows no inhibition of other cytochrome-P450 dependent enzymes of adrenal steroidogenesis [11].

Analytical, diagnostic and therapeutic context of ATAMESTANE

• MATERIALS AND METHODS: In a double-blind study 160 patients from 14 centers were randomized between 2 groups to receive either placebo or the aromatase inhibitor atamestane (1-methyl-androsin-1,4 diene-3 17-dione, 400 mg. daily for 48 weeks) [1].
• In an open multicenter study 49 men (mean age 70.1 years, range 55 to 84) with obstructive BPH were treated with atamestane (3 x 200 mg/day) for 3 months [12].
• Since recent studies in animal models and in men have shown that estrogens might be causally linked to the onset and maintenance of BPH, we examined the effect of 1-methyl-androsta-1,4-diene-3,17-dione (Atamestane), a newly developed aromatase inhibitor, in men with BPH [12].
• In this study, the efficacy of atamestane in suppressing tumor growth was evaluated in comparing with that of a non-steroidal aromatase inhibitor (CGS 16949A, Ciba-Geigy) and ovariectomy [10].

References