Effects of aminoglutethimide on delta 5-androstenediol metabolism in postmenopausal women with breast cancer.
delta-5-Androstene-3 beta, 17 beta-diol has potential estrogenic activity because it is known to bind to receptors and translocate to the nucleus of certain estrogen target tissues. Its role in the biology of breast cancer is unclear. Aminoglutethimide plus hydrocortisone ("medical adrenalectomy") has been used to treat postmenopausal women with metastatic breast cancer. We studied delta 5-androstene-3 beta, 17 beta-diol metabolism in postmenopausal women with breast cancer before and during aminoglutethimide-plus-hydrocortisone therapy, utilizing the constant infusion technique. The metabolic clearance rate for five subjects was 799 +/- 89 liters/24 hr (470 +/- 47 liters/24 hr/sq m) before and 751 +/- 93 liters/24 hr (444 +/- 57 liters/24 hr/sq m) during therapy. Plasma delta 5-androstene-3 beta, 17 beta-diol and delta 5-androstene-3 beta, 17 beta-diol free index decreased despite absence of change in the metabolic clearance rate. Increased dehydroepiandrosterone/delta 5-androstene-3 beta, 17 beta-diol conversion ratios in individual patients suggested an increase in 17 beta-hydroxysteroid dehydrogenase activity during therapy. There were no alterations in the formation of the estrogen precursors testosterone and delta 4-androstene-3,17-dione.
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000616:Aminoglutethimide / Q000627:therapeutic use*; D015114:Androstenediol / Q000378:metabolism*; D000734:Androstenediols / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007700:Kinetics; D008593:Menopause; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D000734:Androstenediols; D000616:Aminoglutethimide; D015114:Androstenediol; D006854:Hydrocortisone