Idiopathic premature adrenarche (IPA) has been linked to later metabolic and reproductive dysfunction, but long-term outcomes into adolescence and adulthood remain incompletely characterized. This systematic review and meta-analysis sought to determine the relationship between IPA and subsequent metabolic risk and hyperandrogenism in premenarcheal adolescent and adult females. Primary endpoints prespecified in the review included body mass index (BMI), markers of insulin resistance (fasting insulin and HOMA-IR), and clinical and biochemical measures of hyperandrogenism.
The authors performed a systematic review and meta-analysis of observational studies. Databases were searched through February 2025 for studies reporting outcomes in females previously diagnosed with IPA after they reached menarche. Data were pooled using random-effects meta-analytic models. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to assess the certainty of the body of evidence for each outcome.
Twenty-one studies met inclusion criteria and were included in the quantitative synthesis. The pooled sample comprised 635 females with a history of IPA and 307 age-matched control participants. The included studies were observational in design; further details on individual study design, follow-up duration, geographic distribution, and participant selection were not reported in the abstract and require consultation of the full text for granular appraisal.
Compared with controls, females with prior IPA had a higher mean BMI. The pooled mean difference reported was 1.4 kg/m2 (95% CI 1.0–1.9), indicating a small but consistent increase in BMI among the IPA group. Markers of insulin resistance were also elevated in the IPA group: fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were higher versus controls, supporting persistence of insulin resistance after menarche in those with earlier IPA.
Clinical and biochemical indices of androgen excess were increased in individuals with prior IPA. The meta-analysis found higher Ferriman–Gallwey scores (a clinical hirsutism scale), elevated dehydroepiandrosterone sulfate (DHEA-S), and higher Free Androgen Index (FAI) in the IPA group compared with controls. These findings point toward a lasting tendency for hyperandrogenism in women who experienced IPA.
Secondary analyses reported additional markers consistent with an early cardiometabolic risk pattern among women with prior IPA. Specifically, the IPA group showed higher triglyceride concentrations, lower high-density lipoprotein (HDL) levels, increased leptin, and greater carotid intima-media thickness. Collectively, these secondary findings suggest an early atherogenic and adiposity-linked phenotype accompanying the insulin-resistant and hyperandrogenic profile.
The authors applied the GRADE framework to rate confidence in pooled estimates. Most outcomes in the review were rated as low certainty. The abstract does not list detailed GRADE ratings for each outcome or the specific reasons (for example, risk of bias, inconsistency, indirectness, imprecision, or publication bias) behind downgrading; those details are available in the full article.
Pooling data from 21 observational studies, the review concludes that females with a history of idiopathic premature adrenarche are at increased long-term risk of insulin resistance and hyperandrogenism, with early signals of an adverse cardiometabolic profile (dyslipidemia, higher leptin, increased carotid intima-media thickness). These results support consideration of long-term monitoring of metabolic and reproductive health in this population to enable early detection and management of cardiometabolic and hyperandrogenic sequelae.
The abstract highlights that GRADE assessment produced mostly low-certainty ratings, implying limitations in the underlying evidence base. The abstract does not provide full methodological detail on heterogeneity between studies, duration of follow-up, confounding adjustment, or other limitations; readers interested in these specifics should consult the full-text manuscript for a detailed risk-of-bias assessment, sensitivity analyses, and study-level characteristics.