Preliminary comparison of net gain in final adult height of girls with early menarche treated with or without gonadotropin-releasing hormone agonist

Background: Early menarche is associated with both physical and psychosocial problems. Based on psychological and physical health considerations, for girls with early menarche, some parents and physicians may elect to use gonadotropin-releasing hormone agonists (GnRHa) to delay menstruation. This study aimed to explore the effects of GnRHa treatment on the final height of girls with early menarche and build the models to predict the final adult height (FAH).

Methods: Girls who experienced menarche between the ages of 8 and 10 years and were diagnosed with idiopathic central precocious puberty (ICPP) at Tianjin Medical University General Hospital between July 2017 and August 2023 were included in this study. Participants were divided into two groups based on treatment strategy: GnRHa-treated and GnRHa-untreated groups. Laboratory parameters including growth factors and basal gonadotropins were tested at diagnosis. The heights and weights of the participants were measured every three months. Bone radiographs of the left hand and wrist were assessed by professional appraisers to determine the bone age (BA), which was measured every 6 months after diagnosis.

Results: Clinical data of 176 girls who experienced early menarche were retrospectively analyzed. For participants in the GnRHa-treated group (n=87), growth velocity (GV) showed significant differences between the first 6 months and second 6 months of treatment (P=0.01; 5.82±2.3 vs. 4.79±2.31 cm, respectively). The height standard deviation score (SDS) and BA (P<0.001) decreased during treatment. The predicted adult height was higher at the end of treatment, but was not statistically different from that at diagnosis (P=0.73). In the linear regression analysis, no significant relationships were observed between GnRHa treatment and net gain (NG) in final height [Model A, adjusted for BA and chronological age (CA) at baseline: P=0.43; Model B, adjusted for Model A plus HtSDS-BA, HtSDS, and BMISDS: P=0.65; Model C, adjusted for Model B plus LH, FSH, and IGF-1: P=0.82]. The generalized additive model (GAM) for NG in final height in GnRHa-treated participants included three independent risk factors: LH/FSH [estimated degrees of freedom (edf) =5.36, P=0.02], GV (edf =4.11, P=0.007), and the bone maturation ratio (BMR) (edf =4.79, P=0.02). GAM performed better than multivariate linear (stepwise) regression in predicting the FAH in GnRHa-treated girls with early menarche.

Conclusions: For girls who experienced menarche between the ages of 8 and 10 years, GnRHa treatment suppressed GV and skeletal maturity. The GAM provides a theoretical basis for pediatric endocrinologists in deciding whether to apply GnRHa treatment, determining the time to withdraw GnRHa treatment, and predicting the FAH of girls with early menarche.