Abiraterone Acetate to Lower Androgens in Women With Classic 21-Hydroxylase Deficiency

Context: Chronic supraphysiological glucocorticoid therapy controls the androgen excess of 21-hydroxylase deficiency (21OHD) but contributes to the high prevalence of obesity, glucose intolerance, and reduced bone mass in these patients. Abiraterone acetate (AA) is a prodrug for abiraterone, a poten...

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Published in:The journal of clinical endocrinology and metabolism 2014-08, Vol.99 (8), p.2763-2770
Main Authors: Auchus, Richard J, Buschur, Elizabeth O, Chang, Alice Y, Hammer, Gary D, Ramm, Carole, Madrigal, David, Wang, George, Gonzalez, Martha, Xu, Xu Steven, Smit, Johan W, Jiao, James, Yu, Margaret K
Format: Article
Language:English
Subjects:
17-alpha-Hydroxyprogesterone - blood
Abiraterone Acetate
Adrenal Hyperplasia, Congenital - blood
Adrenal Hyperplasia, Congenital - drug therapy
Adult
Androgen Antagonists - administration & dosage
Androgen Antagonists - adverse effects
Androgen Antagonists - pharmacokinetics
Androgens - blood
Androstadienes - administration & dosage
Androstadienes - adverse effects
Androstadienes - pharmacokinetics
Androstenedione - blood
Androstenedione - urine
Androsterone - analogs & derivatives
Androsterone - urine
Biological and medical sciences
Desoxycorticosterone - blood
Dose-Response Relationship, Drug
Endocrine Care
Endocrinopathies
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
Humans
Hydrocortisone - administration & dosage
Medical sciences
Treatment Outcome
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
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Summary:Context: Chronic supraphysiological glucocorticoid therapy controls the androgen excess of 21-hydroxylase deficiency (21OHD) but contributes to the high prevalence of obesity, glucose intolerance, and reduced bone mass in these patients. Abiraterone acetate (AA) is a prodrug for abiraterone, a potent CYP17A1 inhibitor used to suppress androgens in the treatment of prostate cancer. Objective: The objective of the study was to test the hypothesis that AA added to physiological hydrocortisone and 9α-fludrocortisone acetate corrects androgen excess in women with 21OHD without causing hypertension or hypokalemia. Design: This was a phase 1 dose-escalation study. Setting: The study was conducted at university clinical research centers. Participants: We screened 14 women with classic 21OHD taking hydrocortisone 12.5–20 mg/d to enroll six participants with serum androstenedione greater than 345 ng/dL (>12 nmol/L). Intervention: AA was administered for 6 days at 100 or 250 mg every morning with 20 mg/d hydrocortisone and 9α-fludrocortisone acetate. Main Outcome Measure: The primary endpoint was normalization of mean predose androstenedione on days 6 and 7 (< 230 ng/dL [
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2014-1258