Gonadotropin-Releasing Hormone Agonist Therapy and Longitudinal Bone Mineral Density in Congenital Adrenal Hyperplasia

J Clin Endocrinol Metab. 2024 Jan 18;109(2):498-504. doi: 10.1210/clinem/dgad514.

Abstract

Context: Children with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used and can decrease bone mineral density (BMD).

Objective: Our aim was to investigate the effect of GnRHa therapy on BMD in a longitudinal study of patients with CAH spanning both childhood and adulthood.

Design and setting: Sixty-one patients with classic CAH due to 21-hydroxylase deficiency (20 treated with GnRHa) were followed with dual-energy X-ray absorptiometry (DXA) scans at puberty onset, attainment of adult height, and during early adulthood.

Main outcome measures: Whole body, lumbar spine, femoral neck, total hip, and distal radius BMD z-score at adult height. Longitudinal BMD and adult height were also assessed.

Results: Twenty patients received GnRHa for an average of 4.5 ± 2 years. There were no differences in BMD between GnRHa-treated and -untreated groups at adult height for all sites. Overall, the follow-up DXA during early adulthood showed decreases in BMD z-scores for whole body (P = .01), lumbar spine (P < .0001), femoral neck (P = .06), total hip (P = .009), and distal radius (P = .05). GnRHa treatment correlated with improved height outcomes compared to predicted height at puberty onset after adjusting for midparental height (P = .02). Patients in both groups achieved similar adult height.

Conclusion: In children with CAH, GnRHa does not compromise BMD. However, BMD decreases with time and during the second and third decades of life is a possible effect of chronic supraphysiologic glucocorticoids. Children with CAH who experience early puberty benefit from GnRHa treatment as evidenced by the positive effect on height.

Keywords: CAH; GnRH agonists; bone density; congenital adrenal hyperplasia; precocious puberty.

MeSH terms

  • Adrenal Hyperplasia, Congenital* / complications
  • Adrenal Hyperplasia, Congenital* / drug therapy
  • Adult
  • Body Height
  • Bone Density
  • Child
  • Gonadotropin-Releasing Hormone
  • Gonadotropins
  • Humans
  • Longitudinal Studies
  • Lumbar Vertebrae
  • Puberty, Precocious*

Substances

  • Gonadotropins
  • Gonadotropin-Releasing Hormone

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