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

Abstract

AA 100-250 mg/d added to replacement hydrocortisone normalized several measures of androgen excess in women with classic 21OHD and elevated serum androstenedione.

Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia

“…Additionally, GnRH antagonist has been successful in improving height in children with 21OHD and precocious puberty 117 . Abiraterone acetate, a potent CYP17A1 inhibitor indicated for testosterone suppression in patients with prostate cancer, when added to physiologic doses of hydrocortisone and fludrocortisone acetate, normalizes AD in adult women with classic 21OHD and elevated androgens 118 . Extended-release hydrocortisone preparations, which might improve compliance and limit the need for more potent glucocorticoids, are being studied 119 .…”

Current and novel approaches to children and young people with congenital adrenal hyperplasia and adrenal insufficiency

“…Abiraterone acetate, a prodrug which is metabolized to abiraterone, is a potent site-directed inhibitor of CYP17A1. A recently published phase 1 study in adult females with CAH reported that abiraterone acetate therapy administered alongside hydrocortisone replacement doses of 8 mg/m 2 /day enabled normalisation of measures of androgen excess with the potential to be used as adjunct therapy [71].…”

“…The recently published phase 1 study reported that low dose abiraterone acetate therapy administered alongside hydrocortisone replacement doses of 8 mg/m 2 /day enabled normalisation of measures of androgen excess [71]. However, the long term safety of these therapies, and their role in the management of CAH warrants future clinical studies.…”

Catalytically Relevant Electrostatic Interactions of Cytochrome P450c17 (CYP17A1) and Cytochrome b5

“…The 17,20-lyase activity of CYP17A1 is the only pathway to androgen biosynthesis known and is an important target for drug discovery. Abiraterone, galeterone, and related steroid azoles (2,36,37) are potent CYP17A1 inhibitors that markedly suppress androgen synthesis, which is desirable for treating prostate cancer (37) and androgen excess disorders such as 21-hydroxylase deficiency (38). These tight-binding heme-directed inhibitors, however, have the undesirable consequence of inhibiting 17-hydroxylase activity as well, which leads to the accumulation of upstream steroids that cause hypertension (39,40) as occurs in genetic 17-hydroxylase deficiency (41), unless combined with glucocorticoid therapy.…”