Influence of aminoglutethimide on plasma levels of estrone sulphate and dehydroepiandrosterone sulphate in postmenopausal breast cancer patients.
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 (E1S). In the present study we used a novel, highly sensitive radioimmunoassay to measure plasma E1S during treatment with AG. Treatment with AG decreased plasma levels of E1S 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 E1 and E2 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 micromol/l (mean suppression to 59.6% of pretreatment values), whereas the ratios of E1S/E1 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 E1S 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.
Geisler
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Department of Oncology, Haukeland University Hospital, Bergen, Norway.
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000616:Aminoglutethimide / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D018567:Breast Neoplasms, Male / Q000097:blood / Q000188:drug therapy; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D011863:Radioimmunoassay
D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D000616:Aminoglutethimide; D004970:Estrone; D019314:Dehydroepiandrosterone Sulfate; C017296:estrone sulfate