Influence of aminoglutethimide on plasma levels of estrone sulphate and dehydroepiandrosterone sulphate in postmenopausal breast cancer patients

• Published in: The Journal of steroid biochemistry and molecular biology 1997-09, Vol.63 (1), p.53-58
• Main Authors: Geisler, Jürgen, Lien, Ernst Asbjørn, Ekse, Dagfinn, Lønning, Per Eystein
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aminoglutethimide - pharmacology; Antineoplastic Agents, Hormonal - pharmacology; Biological and medical sciences; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms, Male - blood; Breast Neoplasms, Male - drug therapy; Dehydroepiandrosterone Sulfate - blood; Enzyme Inhibitors - pharmacology; Estrone - analogs & derivatives; Estrone - blood; Female; General and cellular metabolism. Vitamins; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Postmenopause - blood; Radioimmunoassay
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(97)00071-X

The aromatase inhibitor aminoglutethimide (AG) is widely used in the treatment of advanced breast cancer in postmenopausal women. Apart from the inhibition of estrogen synthesis, previous studies by our group have shown that AG selectively enhances plasma clearance of the estrogen conjugate estrone sulphate (E 1S). In the present study we used a novel, highly sensitive radioimmunoassay to measure plasma E 1S during treatment with AG. Treatment with AG decreased plasma levels of E 1S from a mean pretreatment value of 372.4 to 50.6 pmol/l (mean suppression to 14.5% of pretreatment values) whereas plasma levels of E 1 and E 2 were suppressed to 40.7 and 32.8% of pretreatment values, respectively. Dehydroepiandrosterone sulphate levels decreased from a mean value of 0.8 to 0.5 μmol/l (mean suppression to 59.6% of pretreatment values), whereas the ratios of E 1S E 1 and DHEAS DHEA decreased to 30.8% ( P < 0.001) and 55.5% ( P < 0.005) of pretreatment values, respectively. In conclusion, we found that AG suppressed plasma levels of E 1S more extensively compared to previous studies. The simultaneous suppression of the DHEAS DHEA ratio suggests that AG may influence the disposition of steroid sulphates in general.