Central Precocious Puberty and Psychiatric Disorders

Abstract

Importance: Within the physiological range, early pubertal timing is associated with an increased risk of mental health issues. Previous studies examining the associations of central precocious puberty (CPP) with mental health have yielded inconclusive results.

Objective: To describe the risk for development of psychiatric disorders in patients with CPP and to identify periods during which patients with CPP are at heightened risk of developing psychopathological conditions.

Design, setting, and participants: In this population-based, retrospective cohort study, patients with CPP and matched controls were identified from German health insurance data (approximately 6.5 million individuals) and followed from January 2010 to June 2023. Individuals were included if they had continuous insurance coverage for at least 2 years during the study period. Data were analyzed from July 2024 to March 2025.

Exposure: Diagnosis of CPP.

Main outcomes and measures: Diagnosis of depression, anxiety disorders, oppositional defiant and conduct disorders (ODD/CD), and attention deficit/hyperactivity disorder (ADHD). Incidence rates for psychiatric disorders before and after the diagnosis of CPP were compared between patients and controls exactly matched for sex, birth year interval, insurance period, and obesity.

Results: After the application of validation criteria, 1094 patients with idiopathic CPP (438 born from 2010-2014 [40.0%]; 999 female [91.3%]; 249 [22.8%] with obesity) were identified and compared with 5448 controls (2184 born between 2010-2014 [40.1%]; 4975 female [91.3%]; 1242 with obesity [22.8%]). Compared with controls, patients with CPP were more likely to receive a diagnosis of any mental disorder (270 patients [24.7%] vs 920 controls [16.9%]; adjusted risk ratio [aRR], 1.48; 95% CI, 1.31-1.67), depression (82 patients [7.5%] vs 252 controls [4.6%]; aRR, 1.73; 95% CI, 1.37-2.20), anxiety disorders (88 patients [8.0%] vs 312 controls [5.7%]; aRR, 1.45; 95% CI, 1.16-1.82), ODD/CD (87 patients [8.0%] vs 243 controls [4.5%]; aRR, 1.76; 95% CI, 1.39-2.23), and ADHD (123 patients [11.2%] vs 397 controls [7.3%]; aRR, 1.53; 95% CI, 1.27-1.86). Temporal trends showed increased incidence rates for ODD/CD even before the diagnosis of CPP. For depression and ADHD, incidence rates remained increased for at least 8 years after the initial CPP diagnosis.

Conclusions and relevance: In this retrospective cohort study of patients with CPP, CPP was associated with an increased risk of psychiatric disorders, with evidence supporting long-term mental health outcomes, suggesting that caretakers of children with CPP should be vigilant for the emergence of psychiatric symptoms to initiate psychiatric care at an early stage.

Figure 1.. Identification of Cases and Controls

This figure depicts the application of inclusion and exclusion criteria and identification of valid cases and controls, who were matched for birth year interval, sex, obesity, and insurance period. For each of the diagnoses, the respective International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes are given. The preobservation period refers to the first year of documentation of insurance coverage (ie, either the year 2010, the first year after birth for persons born in 2010 or later, or, in cases with a change of insurance, the first year after enrollment in 1 of the insurance companies covered by the database). Due to the uncertainty of whether a coded diagnosis within the preobservation period referred to a new or preexisting condition, cases with either a coded diagnosis of central precocious puberty (CPP) or 1 of the psychiatric outcomes of interest within the preobservation period were excluded. Please note that the targeted 1:5 ratio between cases and controls was not fully achieved, with fewer than 5 matched controls available for 11 cases of CPP. ^aCategories are not mutually exclusive. ^bDue to restrictions of the database provider, the number of individuals with 1 of these diagnoses was limited to individuals born after the year 2000.

Figure 2.. Risk for Psychiatric Disorders in Patients With Central Precocious Puberty (CPP) Compared With Controls

The risk was defined by the probability that one of the psychiatric diseases of interest was diagnosed in the observation period. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes are given. The adjusted relative risk (aRR) refers to the results of the log-binomial regression model, including the number of routine child and youth examinations as a surrogate marker for health care utilization as a covariate. ADHD indicates attention deficit/hyperactivity disorder; ODD/CD, oppositional defiant and conduct disorders.

Figure 3.. Temporal Trends of Incidence Rates of Psychiatric Diseases

This figure illustrates the incidence rates per 1000 person-years for depression (A), anxiety disorders (B), oppositional defiant and conduct disorders (ODD/CD; C), and attention deficit/hyperactivity disorder (ADHD; D) for patients with central precocious puberty (CPP) and matched controls. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes are given. The dashed lines represent the raw incidence rates per year from the first diagnosis of CPP (ie, 2 years represents the incidence rate for the time frame from the ninth quarter to the 12th quarter after the quarter with the first CPP diagnosis). The solid line represents the 3-year centered moving average (ie, 2 years represents the incidence rate for the time frame from the fifth quarter to the 16th quarter after the first CPP diagnosis). The absolute numbers of events and person-years contributed by patients and controls are given in eTables 2 to 5 in Supplement 1. For incidence rate ratios comparing patients with CPP and controls, see eFigures 10 to 13 in Supplement 1.