Association between 2D:4D digit ratios and metabolic markers and hormonal parameters in children with premature adrenarche: A cross-sectional study from Türkiye.

Background: The appearance of pubic or axillary hair before the age of eight in girls or nine in boys, without other signs of puberty, is defined as premature adrenarche (PA) and may be an early sign of the metabolic syndrome. The second to fourth digit ratio (2D:4D), thought to reflect prenatal androgen exposure, has been associated with a variety of behavioral, metabolic, and hormonal conditions.

Objective: To evaluate the relationship between 2D:4D digit ratios and anthropometric, metabolic, and hormonal parameters in children with PA.

Methods: This cross-sectional study evaluated a Turkish sample of 49 children diagnosed with PA and 41 healthy controls, who were matched for age and gender. Anthropometric measurements, pubertal staging, biochemical and hormonal profiles, and bilateral 2D:4D ratios were recorded. Insulin resistance was assessed using the HOMA-IR, FGIR and QUICKI indices. Correlations between digit ratios and metabolic/hormonal markers were analyzed.

Results: Children with PA had significantly higher Body Mass Index (BMI), waist circumference, fasting glucose, insulin, HOMA-IR and DHEA-S levels, and lower QUICKI and FGIR values compared to controls (p < 0.05). No significant differences were found in 2D:4D ratios between groups. However, in the PA group, the left-hand 2D:4D ratio showed a negative correlation with DHEA-S and systolic blood pressure standard deviation scores (SDS) and a positive correlation with the waist-to-hip ratio (WHR), suggesting early hormonal and cardiovascular alterations in PA. In multivariable regression analysis, only DHEA-S found as an independent negative predictor of the left-hand 2D:4D ratio.

Conclusion: Although 2D:4D ratios may not distinguish between PA and controls, the left-hand 2D:4D ratio may serve as a subtle anthropometric marker reflecting hormonal and metabolic variations in children with PA. In multivariable regression, only DHEA-S remained an independent negative predictor of the left-hand 2D:4D ratio, highlighting the role of adrenal androgens in shaping digit ratio patterns in PA. Given the well-established link between PA and an increased risk of developing metabolic syndrome during adolescence, analysing digit ratios may provide additional value in the early assessment of metabolic risk.