Alterations in the urine excretion of estrogen metabolites in breast cancer women treated with aminoglutethimide

Abstract

The effect of aminoglutethimide treatment on urine estrogen glucuronide excretion was investigated using injections of [4- 14C]estradiol (4 women) or [4- 14Cestrone (2 women). Each patient received 25 μCi of either [4- 14C]estradiol or [4- 14C]estrone as a bolus injection before initiation of aminoglutethimide treatment, and an equal injection following 3–20 weeks on treatment with aminoglutethimide 250 mg q.i.d. with hydrocortisone (50 mg b.i.d. for 2 weeks, then 25 mg b.i.d.). Urine was collected for 24–72 h following each injection. Aminoglutethimide treatment caused significant alterations in the metabolite profiles of estradiol and estrone but with large interindividual variations. [ 14C]Estriol glucuronide excretion was increased by a median value of 48.6%. [ 14C]16α-Hydroxyestrone glucuronide and [ 14C]16-epi-estriol glucuronide excretion was increased by median values of 16.3 and 37.7% respectively, and [ 14C]2-hydroxyestriol glucuronide excretion was increased by a median value of 115.9%. Contrary, excretion of the catechol estrogen glucuronides (2- and 4-hydroxylated metabolites) were reduced (mean reduction of 14.8 and 67.3% respectively). The amount of urine radioactivity excreted as [ 14C]estradiol and [ 14C]estrone glucuronide were consistently reduced by aminoglutethimide treatment (median reduction of 36.8 and 38.2% respectively). These findings suggest aminoglutethimide to stimulate the estrone 16α-hydroxylase and possibly the estrone 16β-hydroxylase located in the hepatic endoplasmic reticulum.