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 cohort study followed from Jan 1st, 1995, to December 31st, 2020. Setting Register-based. Participants All individuals with a diagnosis of precocious puberty in the National Danish Patient Registry (n=9,315, 11% boys) were included. 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). Intervention Precocious puberty including patients registered with an ICD10 diagnosis of central precocious puberty (n=2,955), unspecific premature puberty (n=3,948), premature thelarche (n=937), and premature adrenarche (n=1,475). Main outcome measures Incident psychiatric disorders 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 ADHD (Hazard Ratio (HR): 1.58, 95% confidence interval (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 amongst individuals with precocious puberty.