Influence of Gonadotropin Hormone Releasing Hormone Agonists on Interhemispheric Functional Connectivity in Girls With Idiopathic Central Precocious Puberty

Purpose: The pubertal growth suppressive effects of gonadotropin hormone releasing hormone agonists (GnRHa) are well-known, although it remains unclear if long-term GnRHa treatment influences the brain function of treated children. The present study investigated the differences in the homotopic resting-state functional connectivity patterns in girls with idiopathic central precocious puberty (ICPP) with and without GnRHa treatment using voxel-mirrored homotopic connectivity (VMHC). Methods: Eighteen girls with ICPP who underwent 12 months of GnRHa treatment, 40 treatment-naïve girls with ICPP, and 19 age-matched girls with premature thelarche underwent resting-state functional magnetic resonance imaging using a 3T MRI. VMHC method was performed to explore the differences in the resting-state interhemispheric functional connectivity. The levels of serum pubertal hormones, including luteinizing hormone (LH), follicular-stimulating hormone, and estradiol, were assessed. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales, and VMHC values of different brain regions were performed with the data of the GnRHa treated group. Results: Significant decreases in VMHC of the lingual, calcarine, superior temporal, and middle frontal gyri were identified in the untreated group, compared with the control group. Medicated patients showed decreased VMHC in the superior temporal gyrus, when compared with the controls. Compared to the unmedicated group, the medicated group showed a significant increase in VMHC in the calcarine and middle occipital gyrus. Moreover, a positive correlation was observed between basal LH levels and VMHC of the middle occipital gyrus in medicated patients. Conclusions: These findings indicate that long-term treatment with GnRHa was associated with increased interhemispheric functional connectivity within several areas responsible for memory and visual process in patients with ICPP. Higher interhemispheric functional connectivity in the middle occipital gyrus was related to higher basal LH production in the girls who underwent treatment. The present study adds to the growing body of research associated with the effects of GnRHa on brain function.