Precocious Puberty and Risk of Psychiatric Disorders: A Nationwide Cohort Study Using Prospective Registry Data

CONTEXT: Early menarche within the general population has previously been linked to increased risk of mental health disorders, and such associations are likely to be even stronger in children diagnosed with extremely early puberty (precocious puberty); however, information is sparse. OBJECTIVE: Investigate the association between precocious puberty and psychiatric disorders. DESIGN: A large cohort study included individuals in the National Danish Patient Registry with a diagnosis of precocious puberty from January 1, 1995, to December 31, 2020 (n = 9315, 11% boys), comprising patients registered with an ICD-10 diagnosis of central precocious puberty (n = 2955), unspecific premature puberty (n = 3948), premature thelarche (n = 937), and premature adrenarche (n = 1475). All cases were matched with 5 randomly selected referents from the background population (n = 46 566) according to age, sex, and calendar time (at diagnosis). Incident psychiatric disorders were identified in national health registries (average follow-up time of 7.9 years). RESULTS: Precocious puberty (all cases) was associated with a statistically significant increased risk of attention-deficit/hyperactivity disorder (ADHD) (hazard ratio [HR]: 1.58; 95% CI: 1.36-1.84), anxiety (HR: 1.60; 95% CI: 1.48-1.74), autism (HR: 1.94; 95% CI: 1.67-2.25), depression (HR: 1.41; 95% CI: 1.29-1.53), eating disorders (HR: 1.23; 95% CI: 1.03-1.47), and schizophrenia (HR: 1.72; 95% CI: 1.40-2.10) compared to matched referents. Similar results were observed when stratified by sex, but with greatest effect size among boys. The associations were even stronger among individuals with central precocious puberty. CONCLUSION: Our large register-based cohort study highlights a markedly increased risk of psychiatric disorders among individuals with precocious puberty.