· CPP incidence in Korea has risen steadily over the past decade. Early childhood obesity shows a strong, independent association with CPP, with the highest risk observed in obese boys. These findings highlight the importance of early weight management to reduce CPP risk.

Central precocious puberty (CPP), which is characterized by the early activation of the hypothalamic–pituitary-gonadal axis, has been increasingly reported worldwide in recent decades [1]. In Denmark, for instance, the incidence of CPP in girls rose sixfold from 2.6 to 14.6 per 10,000 between 1998 and 2017, while in boys, it increased fifteenfold from 0.1 to 2.1 per 10,000 during the same period [2].

Among various contributing factors, childhood obesity has emerged as a significant modifiable risk factor for CPP [3,4]. Obesity-related hormonal changes, such as increased leptin levels and insulin resistance, influence the timing of pubertal onset by affecting gonadotropin-releasing hormone (GnRH) secretion [5,6].

In South Korea, the prevalence of childhood obesity continues to rise. A recent study indicated that overweight and obesity rates have increased, especially among South Korean boys [7]. This upward trend raises concerns about obesity’s role in accelerating pubertal development and contributing to the increasing burden of CPP [8].

The present study aims to investigate the prevalence of CPP in the Korean pediatric population using data from the National Health Insurance Service (NHIS). Furthermore, by linking this dataset with the national Infant/Toddler Health Check-up Program (ITHCP), we explore the association between early childhood body mass index (BMI) and the subsequent development of CPP. This study seeks to provide population-level evidence on the influence of early growth patterns on pubertal timing, which may contribute to risk stratification and early intervention strategies.

CPP was defined as the development of secondary sexual characteristics before age 8 in girls (e.g., thelarche) and before age 9 in boys, reflecting early activation of the hypothalamic-pituitary-gonadal axis. Diagnosis was confirmed using a GnRH stimulation test, with a peak luteinizing hormone (LH) level ≥5 IU/L considered pubertal.

We utilized 2 nationwide datasets: NHIS claims data from 2012 to 2020 and ITHCP data from 2013 to 2016. NHIS includes comprehensive diagnostic codes and prescription records for the entire Korean population, while ITHCP contains longitudinal anthropometric and screening data for children aged 2–6 years.

CPP was operationally defined as children who (1) had International Classification of Diseases, 10th Revision codes E22.8 or E30; (2) were officially registered under the NHIS CPP registry program; (3) initiated treatment with a GnRH agonist—leuprolide acetate, triptorelin pamoate, or triptorelin acetate—before age 8 in girls and before age 9 in boys; and (4) received treatment for at least 1 year under NHIS reimbursement. This definition was intended to exclude cases of early puberty that did not meet diagnostic or treatment duration thresholds.

From 2012 to 2020, 616,923 children were identified in the NHIS database with puberty-related diagnoses. After excluding those with missing age or sex data, age beyond the CPP diagnostic window at treatment initiation, and those with confounding medical conditions (e.g., epilepsy, cerebral palsy, psychiatric disorders, growth hormone deficiency, thyroid disease, diabetes, tumors, rare diseases), a final cohort of 195,892 children (21,548 males; 174,344 females) was retained (Fig. 1).

The annual incidence of CPP was calculated per 100,000 population and stratified by sex and year. Trends in incidence between 2012 and 2020 were assessed using the Cochran-Armitage trend test.

The ITHCP initially included 3,763,208 children aged 2–6 years between 2013 and 2016. We selected children who had undergone at least 3 of the 8 scheduled health check-ups. Those with congenital or chronic diseases (e.g., epilepsy, psychiatric illness, endocrine disorders, rare diseases) were excluded, resulting in 1,468,004 eligible participants.

Data from NHIS and ITHCP were matched using encrypted individual identifiers, allowing longitudinal tracking of each child's early BMI and later CPP diagnosis. In total, 35,766 children (1,814 males; 33,952 females) were successfully linked and included in the final analysis cohort (Fig. 1).

Children were classified by BMI percentile using Korean age- and sex-specific growth standards into 4 categories: underweight (<5th percentile), normal weight (5th–84th percentile, reference group), overweight (85th– 94th percentile), and obese (≥95th percentile).

To evaluate the association between early BMI and CPP, we performed multivariable logistic regression analyses stratified by sex. Odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated to estimate risk across BMI categories.

All analyses were conducted using IBM SPSS Statistics ver. 23.0 (IBM Co., USA). A P-value of <0.05 was considered statistically significant.

This study was reviewed and approved by the Institutional Review Board of the National Health Insurance Service Ilsan Hospital (IRB No. 2022-09-011).

From 2012 to 2020, the incidence of CPP in boys aged 6–8 years increased from 4.3 to 33.7 per 100,000 (Fig. 2, blue line). When a broader definition that includes early puberty (ages 6–9 years) was used, the incidence rose from 9.5 to 119.8 per 100,000 over the same period (Fig. 2, orange line).

In girls aged 5–7 years, the incidence of CPP increased from 301.0 per 100,000 in 2012 to 594.2 per 100,000 in 2020 (Fig. 3, blue line). When early puberty cases (ages 5–8 years) were included, the incidence rose from 594.6 to 1800.3 per 100,000 (Fig. 3, orange line).

As shown in Fig. 4, annual incidence rates of CPP increased steadily from 2012 to 2020 in both sexes. In boys, the incidence rose from 4.1 to 55.1 per 100,000 (P for trend <0.0001), and in girls from 270.6 to 919.9 per 100,000 (P for trend <0.0001).

Fig. 5 presents the average age-specific incidence of CPP from 2012 to 2020, stratified by sex. In girls, CPP incidence increased steadily beginning at age 5, with a sharp rise observed through age 8. In boys, the incidence showed a more gradual upward trend beginning at age 7 and extending through age 9. Trend analysis revealed statistically significant increases across ages in both sexes (P for trend <0.0001).

Multivariable logistic regression demonstrated a significant association between early childhood BMI and CPP (Table 1). Compared to the normal-weight group (5th–84th percentile), underweight children (<5th percentile) had reduced odds of CPP (OR: 0.788 in males, 0.657 in females; both P<0.0001). Overweight children (85th–94th percentile) had higher odds (OR: 1.744 in males, 1.544 in females), and the obese group (≥95th percentile) showed the highest risk (OR: 2.573 in males, 2.025 in females; all P<0.0001).

This study examined nationwide trends in the incidence of CPP in Korea and analyzed the relationship between early childhood BMI and CPP development using linked data from NHIS and ITHCP. Between 2012 and 2020, CPP incidence steadily increased in both sexes, with a sharper rise observed in girls. In boys aged 6–8 years, the incidence rose more than sevenfold, while in girls aged 5–7 years, it nearly doubled during the same period. These findings are consistent with previous population-based studies from other countries reporting a rising burden of CPP over recent decades [1,2,9].

Age-specific analysis revealed that in girls, the incidence of CPP began to rise from age 5 and peaked at age 8, whereas in boys, a gradual increase was observed starting at age 7. While these patterns reflect the natural distribution of pubertal onset, they also highlight potential diagnostic clustering around guideline-based cutoff ages. Although administrative criteria such as age thresholds and treatment history help standardize CPP identification, distinguishing CPP from early but normal pubertal development remains a clinical challenge, particularly in older age groups. In this context, experienced clinical judgment is still essential, and consultation with a pediatric endocrinologist is recommended to ensure accurate diagnosis and appropriate management.

Multivariable analysis demonstrated a strong association between early childhood obesity and the risk of CPP [1,7]. Compared to normal-weight children (5th– 84th percentile), those in the overweight (85th–94th percentile) and obese (≥95th percentile) categories had significantly higher odds of developing CPP regardless of sex. Notably, the magnitude of association was greater in boys than in girls, with obese boys showing 2.57-fold higher risk compared with their normal-weight counterparts. Importantly, this study suggests that increased BMI during the growth period between ages 2 and 6 may contribute to earlier pubertal onset, emphasizing the importance of early weight trajectory as a predictive factor.

While the impact of adiposity on pubertal timing in girls is well documented, the mechanisms underlying the observed association in boys are less clearly understood and may be bidirectional [3,10]. Increased fat mass can promote earlier puberty through several pathways, including elevated leptin and insulin levels and increaTable sed aromatase activity, which converts androgens to estrogens and may stimulate the hypothalamic-pituitary-gonadal axis [3,11,12]. However, other studies have suggested that severe obesity in boys may suppress testosterone levels and delay pubertal progression [13]. Additionally, obese boys may show lower peak LH responses in GnRH stimulation testing, complicating the clinical diagnosis of CPP. These findings indicate that while obesity appears to be a significant risk factor for CPP in boys at the population level, individual hormonal profiles and the degree of adiposity may produce heterogeneous outcomes [13]. Further mechanistic studies are required to clarify these pathways.

Fig. 5 demonstrates the average age-specific distribution of CPP incidence over a 9-year period. The observed age-related increase in diagnosis suggests consistent clustering of CPP cases near the guideline-based age thresholds. In girls, the majority of cases were diagnosed between ages 6 and 8, while in boys, diagnoses increased gradually from age 7 onward. These findings imply that diagnostic activity is concentrated around ages where clinical suspicion for CPP is highest, potentially reflecting both biological onset patterns and heightened clinical vigilance.

Notably, the steep rise observed in incidence when broader age ranges are included, such as 6–9 years in boys and 5–8 years in girls, suggests that early puberty cases may be increasingly captured under the label of CPP. This diagnostic overlap becomes more prominent near the upper end of the age criteria, where distinguishing true CPP from normal early pubertal onset is clinically challenging [14-16]. Since administrative definitions based on age, diagnosis codes, and treatment claims may not fully align with biological or developmental markers, these trends raise concerns regarding diagnostic accuracy and the potential for overtreatment [16].

In this context, the clinical role of pediatric endocrinologists becomes particularly crucial. Accurate diagnosis of CPP requires not only biochemical confirmation and radiologic evaluation, but also detailed assessment of pubertal progression and growth trajectory. Particularly in borderline cases, physician expertise is essential to distinguish physiologic variants from pathologic pubertal activation. Therefore, clinical decision-making should be guided by experienced specialists to ensure appropriate and individualized management to minimize both under- and overtreatment.

This study has several strengths, including the use of 2 large-scale, population-based databases and a clearly defined operational algorithm for CPP identification. However, some limitations must be acknowledged. First, data on socioeconomic status, birth weight, and small-for-gestational-age status were not available and thus could not be adjusted for in the models. Second, the use of administrative diagnostic codes and prescription history may have led to misclassification, although the requirement for ≥1 year of GnRH agonist treatment was used to reduce false positives.

In conclusion, the incidence of CPP increased significantly in both boys and girls over the past decade in Korea. Early childhood obesity, particularly BMI increases during ages 2 to 6, was a strong and independent risk factor for CPP, with a stronger association observed in boys. These findings underscore the importance of early weight management strategies and public health efforts to mitigate the rising burden of precocious puberty. Further studies are needed to explore the mechanistic differences in how obesity influences pubertal timing by sex and to refine risk prediction using a broader set of clinical and sociodemographic variables.