Central precocious puberty (CPP) is characterized by the premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, leading to the early onset of secondary sexual characteristics before the age of 8 in girls and 9 in boys, along with an advanced skeletal age [1-3]. Recent studies across various countries have observed an elevation in CPP incidence [4]. Particularly in South Korea, the annual incidence has escalated dramatically—a 17.2-fold increase between 2008 and 2020. The rise has been particularly pronounced among boys, with an 83.3-fold increase [5]. The gonadotropin-releasing hormone (GnRH) stimulation test is considered the gold standard for assessing HPG axis activation and CPP diagnosis [1,6-8]. A luteinizing hormone (LH) concentration of ≥5.0 IU/L following intravenous GnRH stimulation is generally recognized as indicative of HPG axis activation [1].

However, GnRH (gonadorelin, Relefact, Manufacturer, Sanofi-Aventis, Gentilly, France), which was previously a common choice for this test, has recently faced commercial limitations, leading to the increased use of the GnRH agonist (GnRHa, triptorelin acetate, Decapeptyl, Manufacturer, Ferring, Saint Prex, Switzerland) as a preferred alternative. Several studies have shown that the triptorelin stimulation test offers diagnostic accuracy comparable to the gonadorelin stimulation test in girls [6-9]. However, to the best of our knowledge, no studies have yet confirmed whether this holds true for boys. Furthermore, there is a lack of data on the timing of peak LH levels following GnRHa stimulation in boys.

This retrospective study analyzed boys evaluated for precocious puberty at the Division of Pediatric Endocrinology at Hanyang University Hospital in Seoul and Guri, between March 2019 and August 2024. The study included all patients who underwent a GnRH or GnRHa stimulation test and showed advanced bone age (BA), with testicular volumes confirmed to be ≥4 mL before the age of 9. For patients whose initial visit occurred at age 9 or older, inclusion criteria were based on clinical suspicions of a testicular volume ≥4 mL before age 9, based on findings of a volume of ≥6 mL before age 9.5 or ≥8 mL before age 10.

A total of 55 boys met these criteria: 23 underwent a GnRH stimulation test, and 32 underwent a GnRHa stimulation test. From these, 17 boys from each group (totaling 34) were matched in a 1:1 ratio using propensity score matching based on BA. After matching, the standardized mean difference was 0.026, indicating negligible covariate imbalance between the 2 groups, and multiple regression analysis showed no significant differences in any clinical characteristics between the groups (P>0.05). Differences between the 2 groups were evaluated using the Mann-Whitney U-test.

The clinical characteristics, including age, height, weight, body mass index, testicular volume, and basal levels of LH, and testosterone, showed no significant differences between the 2 groups, except for follicle-stimulating hormone, which has relatively less clinical relevance (Table 1).

In these 2 groups, a significant difference in peak LH levels was observed. In the gonadorelin group, the peak LH level was 9.70 mIU/mL, whereas it was 19.55 mIU/mL in the triptorelin group (Table 2).

Additionally, the timing of the peak LH levels differed between the 2 groups. In the gonadorelin test group, 12 out of 17 participants exhibited a peak at 45 minutes. In contrast, in the triptorelin test group, LH levels tended to continuously increase over time, indicating that the peak occurred at least 90-minute poststimulation. This finding suggests that a longer stimulation period beyond 90 minutes might be necessary to accurately capture the peak LH value in triptorelin tests.

The recent increase in the incidence of CPP coincided with the shift from the gonadorelin stimulation test to the triptorelin stimulation test in 2021 [10], suggesting a cautious hypothesis that the higher peak LH values observed in the triptorelin tests may have contributed to a greater likelihood of CPP diagnosis. In this study, the peak LH values in boys during stimulation tests using triptorelin were significantly higher than those obtained with gonadorelin tests. Thus, even when positive results are obtained using the triptorelin test, cautious interpretation is essential.

The diagnosis of CPP requires a positive result in the GnRH or GnRHa stimulation test which is necessary but not sufficient on its own. For an accurate diagnosis, it is crucial to confirm clinical evidence.

The limitations of our study include the small sample size for each group, and the fact that gonadorelin and triptorelin stimulation tests were not performed on the same individuals.

In conclusion, the triptorelin stimulation test shows limitations as a reliable alternative to the traditional gonadorelin stimulation test in boys. Results from the triptorelin test should be interpreted with caution due to these differences.