Pharmacotherapeutic strategies for the management of congenital adrenal hyperplasia.

INTRODUCTION

Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess adrenal androgen production. Current management relies on adrenal hormone replacement, however, achieving adequate androgen suppression often requires supraphysiologic glucocorticoid dosing with a risk of long-term morbidity.

AREAS COVERED: This review discusses current evidence on pharmacotherapeutic strategies for 21OHD, including evolving glucocorticoid formulations and delivery methods, as well as both established and emerging non-glucocorticoid therapies. The articles included in this review were identified through a PubMed search conducted up to April 2026.

EXPERT OPINION: Glucocorticoids remain the cornerstone of therapy but are inherently limited by dose-dependent adverse effects. Emerging non-glucocorticoid agents such as the corticotropin-releasing factor type 1 (CRF1) receptor and melanocortin type 2 receptor (MC2R) antagonists represent the most clinically advanced strategy to reduce androgen excess, while enabling glucocorticoid dose reduction, and are likely to redefine standard care. Upstream targeting of the hypothalamic-pituitary-adrenal axis is expected to supersede downstream anti-androgen approaches. Future management will likely involve combination pharmacotherapies directed at the hypothalamic axis. Eventual use of CYP21A2 gene therapies may offer disease modification.