Post-COVID-19 rise in central precocious puberty: an integrative Review

The COVID-19 pandemic was associated with a marked increase in central precocious puberty (CPP), particularly among girls, with pooled estimates showing higher odds during pandemic than pre-pandemic periods. The available evidence supports a reproducible epidemiological signal, but it does not establish a single causal mechanism. This narrative review synthesizes epidemiological findings, clinical features, and proposed mechanisms, including sedentary behavior, weight gain, increased screen exposure, sleep and melatonin rhythm disruption, psychological stress, altered healthcare-seeking behavior, and environmental endocrine-disrupting chemicals (EDCs). Recent high-throughput toxicology data indicate that selected environmental compounds, including musk ambrette and some quaternary ammonium compounds (QACs), can activate human KISS1R- or GnRHR-related signaling in experimental systems. However, pediatric exposure levels, internal dose, target-tissue concentrations, and disease-level causality remain unproven. We therefore frame these chemical findings as a hypothesis-generating exposomic perspective rather than as an established explanation for pandemic-era CPP. A cautious integrative model may help reconcile the strong female predominance, limited mean BMI shift, and temporal association with lockdown-related exposures, while defining testable priorities for future cohort, exposure, and mechanistic studies.