Comments on “Comparative Analysis of Girls With Slowly Progressive Central Precocious Puberty vs. Rapidly Progressive Central Precocious Puberty: Single-Center Experience”

Dear Editor,

I read with great interest the recent article by Dincer et al. ^[1] entitled “Comparative Analysis of Girls With Slowly Progressive Central Precocious Puberty vs. Rapidly Progressive Central Precocious Puberty: Single-Center Experience.” The authors present a single-center experience involving a large cohort of 406 girls, providing useful information on the clinical and laboratory parameters that differentiate these two distinct clinical courses. I commend the authors for their clear delineation of the diagnostic criteria and their practical emphasis on the bone age-to-chronological age (BA/CA) ratio as a predictive marker of rapid progression. The identification of a specific cutoff value of 1.18 for the BA/CA ratio offers a potentially useful tool for clinicians navigating the often-challenging decision of whether to initiate gonadotropin-releasing hormone agonist (GnRHa) therapy or pursue conservative observation.^[1]

While the findings of Dincer et al. ^[1] are significant, I believe it is essential to interpret them within the broader context of evolving epidemiological trends in pubertal timing. As noted in a systematic review and meta-analysis by Eckert-Lind et al., ^[2] there has been a worldwide secular trend toward earlier thelarche, with the age of onset decreasing by nearly three months per decade from 1977 to 2013. This downward shift in the timing of initial pubertal signs presents a clinical conundrum: distinguishing between pathological precocity requiring intervention and the lower end of the shifting physiological norm. The SP-CPP group included 252 patients, compared to 154 patients in the RP-CPP group in the study by Tetik Dincer et al. [1]. This may reflect the fact that many girls presenting with early pubertal signs do not show rapid progression requiring treatment.

The distinction between SP-CPP and RP-CPP is pivotal because the management approaches differ fundamentally. International perspectives, such as the updated review by Cheuiche et al., ^[3] emphasize that the primary goals of treating CPP are the preservation of final adult height and the alleviation of psychosocial stress. However, in cases of SP-CPP, in which height potential is often preserved without intervention, the risk of overtreatment must be carefully weighed. Similarly, the 2022 Clinical Practice Guidelines by the Korean Society of Pediatric Endocrinology recommend a meticulous observation period of 3 to 6 months to evaluate the tempo of pubertal progression before confirming a diagnosis or initiating therapy.^[4] This “watchful waiting” approach aligns with the retrospective findings of Dincer et al., ^[1] which suggest that initial clinical snapshots, specifically thelarche stage and bone age advancement, are strong predictors of the subsequent clinical course.

Furthermore, the decision to treat should consider long-term health outcomes beyond immediate auxological parameters. While GnRHa therapy is the gold standard for RP-CPP, its long-term safety profile is important to consider when using it in borderline or slowly progressive cases. Karavani et al. ^[5] examined adult women previously diagnosed with CPP and found no statistically significant difference in the prevalence of polycystic ovary syndrome (PCOS) or metabolic comorbidities between those treated with GnRHa and those who were not. These findings are reassuring and support the safety of treatment when indicated; however, they also implicitly support the safety of nonintervention in SP-CPP cases, as untreated women did not show a higher prevalence of the assessed metabolic or reproductive outcomes compared with their treated counterparts.^[5] Thus, accurate stratification of patients using tools such as the BA/CA ratio proposed by Tetik Dincer et al. ^[1] becomes even more critical to avoid unnecessary medicalization of healthy children.

While the BA/CA ratio cutoff of 1.18 is a promising metric, I suggest that external validation in multicenter cohorts is necessary before it can be universally adopted. The interplay between obesity and bone maturation is a known confounder in pediatric endocrinology. Although Tetik Dincer et al. ^[1] reported comparable obesity rates between their SP-CPP and RP-CPP groups, the literature indicates that a higher body mass index (BMI) is associated with earlier pubertal development.^[2] Consequently, the specificity of a BA/CA threshold might vary across populations with different nutritional statuses or obesity prevalence. Additionally, while the study effectively highlights the static BA/CA ratio, the dynamic assessment of growth velocity remains a cornerstone of diagnosis. As highlighted in the Korean guidelines, accelerated growth velocity is a key indicator of rapid progression that warrants treatment.^[4] Integrating the static BA/CA marker with dynamic growth velocity data could potentially improve predictive sensitivity for identifying RP-CPP.

An additional methodological consideration relates to the potential for incorporation bias. Since bone age advancement was one of the clinical features considered during the classification of rapidly progressive CPP, the subsequent identification of the BA/CA ratio as an independent predictor of RP-CPP may partly reflect overlap between the predictor and the outcome definition. Future prospective studies using progression criteria less dependent on bone age advancement may help clarify the true predictive value of the BA/CA ratio.

In conclusion, the study by Dincer et al. ^[1] makes a substantial contribution to the field by providing a pragmatic, evidence-based parameter for stratifying girls with central precocious puberty. Their research underscores the importance of a customized diagnostic strategy that effectively distinguishes between rapidly progressive cases that necessitate intervention and slowly progressive variants that can be monitored safely. I advocate for future studies to confirm the suggested BA/CA cutoff across various populations and to delve deeper into the relationship between secular trends in puberty, obesity, and diagnostic thresholds. These initiatives will improve risk stratification methods and bolster evidence-based, personalized decision-making in the treatment of girls exhibiting early pubertal development.

Conflict of Interest

The authors declare that there is no conflict of interest.

Financial Disclosure

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Use of AI for Writing Assistance

No artificial intelligence-assisted technologies were used in the preparation of this manuscript.