Document Detail


The endocrine effects of long-term treatment with mifepristone (RU 486).
MedLine Citation:
PMID:  1646217     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer.
Authors:
S W Lamberts; J W Koper; F H de Jong
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  73     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1991 Jul 
Date Detail:
Created Date:  1991-07-12     Completed Date:  1991-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  187-91     Citation Subset:  AIM; IM; J    
Affiliation:
Department of Medicine, Erasmus University, Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / blood
Adult
Aged
Androgens / biosynthesis*
Androstenedione / blood
Brain Neoplasms / drug therapy*
Circadian Rhythm
Corticotropin-Releasing Hormone / diagnostic use
Dexamethasone / diagnostic use
Estradiol / blood
Estrogens / biosynthesis*
Female
Humans
Hydrocortisone / blood,  urine
Male
Meningioma / drug therapy*
Middle Aged
Mifepristone / adverse effects*,  therapeutic use
Nausea / chemically induced
Vomiting / chemically induced
Chemical
Reg. No./Substance:
0/Androgens; 0/Estrogens; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; 50-28-2/Estradiol; 63-05-8/Androstenedione; 84371-65-3/Mifepristone; 9002-60-2/Adrenocorticotropic Hormone; 9015-71-8/Corticotropin-Releasing Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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