INFLUENCE OF AMINOGLUTETHIMIDE ON PLASMA-LEVELS OF ESTRONE SULFATE AND DEHYDROEPIANDROSTERONE-SULFATE IN POSTMENOPAUSAL BREAST-CANCER PATIENTS

The aromatase inhibitor aminoglutethimide (AG) is widely used in the t reatment of advanced breast cancer in postmenopausal women. Apart from the inhibition of estrogen synthesis, previous studies by our group h ave shown that AG selectively enhances plasma clearance of the estroge n conjugate estrone sulphate (E1S). In the present study we used a nov el, highly sensitive radioimmunoassay to measure plasma E1S during tre atment 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 E-1 and E-2 we re 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 mu mol/l (mean suppression to 59.6% of pretreatment values) , whereas the ratios of E1S/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 E1S more ext ensively compared to previous studies. The simultaneous suppression of the DHEAS/DHEA ratio suggests that AG may influence the disposition o f steroid sulphates in general. (C) 1997 Elsevier Science Ltd. All rig hts reserved.