From Premature Adrenarche to Adult Metabolic Risk and Hyperandrogenism: A Systematic Review and Meta-Analysis
Thais Milioni Luciano, Mariana Peduti Halah, Luís Eduardo Cruvinel Pinto, Mayara Souza Ribas Castor, Vânia dos Santos Nunes-Nogueira, Sonir Rauber AntoniniAbstract
Context
Idiopathic premature adrenarche (IPA) has been associated with a higher risk of metabolic and reproductive dysfunction, but long-term/adult outcomes remain incompletely known.
Objective
To assess the relationship between IPA and metabolic syndrome, as well as polycystic ovarian syndrome, in premenarcheal adolescent and adult women.
Methods
We conducted a systematic review and meta-analysis of observational studies reporting outcomes in females with IPA after menarche. Databases were searched through February 2025. Primary outcomes included BMI, insulin resistance markers, and clinical and biochemical markers of hyperandrogenism. Data were pooled using random-effects models. The GRADE approach was applied to assess the certainty of evidence.
Results
A total of 21 studies comprising 635 females with IPA and 307 age-matched controls were included. Compared to controls, IPA individuals showed significantly higher BMI (MD: 1.4; CI: 1.0 to 1.9), fasting insulin, and HOMA-IR, indicating persistent insulin resistance. Markers of hyperandrogenism, including Ferriman-Gallwey score, DHEAS, and FAI, were also elevated. Secondary analyses revealed higher triglycerides, lower HDL, increased leptin, and greater carotid intima-media thickness, supporting an early pattern of cardiometabolic risk. GRADE assessment rated most outcomes as low certainty.
Conclusion
Women with a history of IPA are at increased risk of long-term insulin resistance and hyperandrogenism, with early signs of adverse cardiometabolic profiles. These findings support the need for long-term monitoring in this population.