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 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 [