Intramuscular and subcutaneous gonadotropin-releasing hormone agonist tests for central precocious puberty in girls: a randomized controlled trial

Background: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis. Although the standard intravenous gonadotropin-releasing hormone (GnRH) stimulation test is often inaccessible, a subcutaneous (SC) GnRH analogue (GnRHa) test is used. However, the conventional SC route presents logistical challenges including prolonged observation times and the need for multiple blood draws. Thus, identifying a more efficient administration route could optimize clinical workflows and enhance patient comfort. This study aimed to determine whether intramuscular (IM) administration is comparable to SC administration by analyzing the time to peak luteinizing hormone (LH) levels. Purpose: To evaluate and compare the time to peak LH levels and diagnostic timing of IM versus SC GnRH stimulation tests in girls with CPP. Methods: This randomized controlled trial enrolled 92 girls with suspected CPP. Participants were assigned via 2:1 block randomization to receive 100 mcg triptorelin acetate via SC (n=62) or IM (n=30) injection. Serial blood samples for LH and follicle-stimulating hormone were collected at 0, 30, 60, 90, and 120 minutes. Results: There were no significant differences between the 2 groups in demographic characteristics. Peak LH responses were most frequent at 30 minutes in both groups (IM, 33.3%; SC, 35.5%; P=0.88). The mean LH levels at 30, 60, 90, and 120 minutes did not differ significantly between groups. Diagnostic confirmation of CPP occurred within 30 minutes in 96.7% and 96.8% of patients in the IM and SC groups, respectively. Conclusion: The IM GnRH stimulation test was comparable to the standard SC test in terms of LH response magnitude and timing.