Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency

Richard J. Auchus, Elizabeth O. Buschur, Alice Y. Chang, Gary D. Hammer, Carole Ramm, David Madrigal, George Wang, Martha Gonzalez, Xu Steven Xu, Johan W. Smit, James Jiao, Margaret K. Yu

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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 [-8 nmol/L)] in greater than 80% of participants. Secondary end points included serum 17-hydroxyprogesterone and testosterone (T), electrolytes, plasma renin activity, and urine androsterone and etiocholanolone glucuronides. Results: With 100 mg/d AA, mean predose androstenedione fell from 764 to 254 ng/dL (26.7- 8.9 nmol/L). At 250 mg/d AA, mean androstenedione normalized in five participants (83%) and decreased from 664 to 126 ng/dL (23.2- 4.4 nmol/L), meeting the primary end point. Mean androstenedione declined further during day 6 to 66 and 38 ng/dL (2.3 and 1.3 nmol/L) at 100 and 250 mg/d, respectively. Serum T and urinary metabolites declined similarly. Abiraterone exposure was strongly negatively correlated with mean androstenedione. Hypertension and hypokalemia were not observed. Conclusion: AA 100-250 mg/d added to replacement hydrocortisone normalized several measures of androgen excess in women with classic 21OHD and elevated serum androstenedione.

Original languageEnglish (US)
Pages (from-to)2763-2770
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number8
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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