Aromatase Inhibitor Increases the Height of Patients with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Objective: Patients with 21-hydroxylase deficiency (21OHD) typically suffer from short stature due to early exposure to adrenal-derived androgen. The aim of this study was to investigate whether adding aromatase inhibitor (AI) to gonadotropin-releasing hormone (GnRH) analogue (GnRHa) and recombinant human growth hormone (rhGH) therapy would increase the height of patients with 21OHD. Methods: This retrospective study included 15 patients with 21OHD. The AI/GnRHa/rhGH group consisted of 9 patients, who were treated with AI for at least 12 months in addition to GnRHa/rhGH therapy. The other 6 patients, who received GnRHa/rhGH therapy only, were defined as the GnRHa/rhGH group. Results: Patients were 6.3 ± 1.7 years old, and 7/15 of patients were male. Among them, 12 patients exhibited simple virilization type, and 3 patients were salt-wasting type. In the AI/GnRHa/rhGH group, patients were 6.6 ± 2.0 years old when AI therapy was initiated. Their bone age was 5.9 ± 2.2 years ahead of their chronological age. They received the AI letrizole for an average of 25.1 months (range, 12 to 37 months). In the GnRHa/rhGH group, the patients were 5.9 ± 0.9 years old when they started GnRHa/rhGH therapy, and their bone age was 6.2 ± 1.7 years ahead of their chronological age. Patients received GnRHa/rhGH therapy for an average of 24.5 months (range, 12 to 41 months). The predicted final height increased from 145.9 ± 7.9 to 158.0 ± 8.4 cm in the AI/GnRHa/rhGH group (P = .001, compared with the baseline) and from 141.7 ± 2.7 to 150.7 ± 4.7 cm in the GnRHa/rhGH group (P = .001, compared with the baseline). Bone age progression was 0.15 ± 0.05 per year versus 0.44 ± 0.13 per year in the two groups, respectively (P = .032). Conclusion: Addition of letrizole to GnRHa/rhGH therapy significantly delays bone maturation and may increase the final height.