Preservation of androgen secretion during estrogen suppression with aminoglutethimide in the treatment of metastatic breast carcinoma

The Journal of Clinical Investigation
E SamojlikR J Santen

Abstract

We evaluated the comparative effects of aminoglutethimide (AG) on androgen and estrogen levels estrone ([E1], estradiol [E2], plasma dehydroepiandrosterone-sulfate [DHEA-S], testosterone [T], dihydrotestosterone [DHT], delta 4-androstenedione [delta 4-A]), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin in postmenopausal patients with breast cancer randomly allocated to either AG treatment or bilateral surgical adrenalectomy as a control group. In response to either treatment, the plasma levels of E1 fell 62-75% (P less than 0.001) and urine E1 85.7-88.7% (P less than 0.001) in all study days over a 12-wk period. Similarly, the concentrations of E2 in plasma and urine fell 40-72% without statistically significant differences between the two treatment modalities. The relatively weak androgen, DHEA-S, was reduced by 92% (877.3 +/- 184.6 to 71.8 +/- 14.5 ng/ml) at 12 wk in women treated with AG, but suppressed nearly 99% (1,151 +/- 262 to 5.8 +/- 3.3 ng/ml) in adrenalectomized women. At all time points after treatment, the DHEA-S levels were significantly higher in patients receiving AG. Plasma concentrations of the potent androgens, T and DHT, were also relatively preserved during AG treatment. T level...Continue Reading

References

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Citations

Jan 1, 1986·Breast Cancer Research and Treatment·S J SantnerR J Santen
Oct 1, 1989·Journal of Steroid Biochemistry·P E LønningD Ekse
Nov 1, 1995·Critical Reviews in Oncology/hematology·E Lønning, E A Lien
Dec 20, 1980·Lancet·M L Friedlander
Dec 20, 1980·Lancet·S Kohl, L K Pickering
Jul 10, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P E Lønning
Apr 30, 2013·Endocrine-related Cancer·Per Eystein Lønning, Hans Petter Eikesdal
Jan 1, 1990·Journal of Enzyme Inhibition·R J Santen
Jul 16, 2008·Expert Opinion on Drug Metabolism & Toxicology·Per Eystein Lønning, Jürgen Geisler
Oct 30, 2009·Acta Oncologica·Per Eystein Lønning
Oct 8, 2009·The Journal of Steroid Biochemistry and Molecular Biology·P E Lønning, J Geisler
Jan 1, 1986·Critical Reviews in Oncology/hematology·A M Brodie, R J Santen
Sep 1, 1984·Cancer Treatment Reviews·R C Stuart-Harris, I E Smith
Dec 1, 1983·Clinical Endocrinology·A VermeulenJ C Heuson
Aug 28, 2014·Steroids·Per Eystein Lønning
May 1, 1988·Journal of Andrology·A IranmaneshG Lizarralde
Jul 5, 2017·Frontiers in Pharmacology·Tea Lanišnik RižnerCsilla Özvegy-Laczka
Aug 1, 1980·The American Journal of Physiology·R J SantenE Badder
Apr 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jürgen Geisler, Per Eystein Lønning

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