Digit ratio (2D:4D) and congenital adrenal hyperplasia (CAH): Systematic literature review and meta-analysis

The ratio of length between the second and fourth fingers (2D:4D) is commonly used as an indicator of prenatal sex hormone exposure. Several approaches have been used to try to validate the measure, including examining 2D:4D in people with congenital adrenal hyperplasia (CAH), a suite of conditions characterised by elevated adrenal androgen production secondary to defective steroidogenesis. We present here a systematic review that examines the relationship between these two variables. Twelve articles relating to nine CAH cohorts were identified, and 2D:4D comparisons have been made between cases and controls in eight of these cohorts. Altogether, at least one 2D:4D variable has been compared between n=251 females with CAH and n=358 unaffected females, and between n=108 males with CAH and n=204 unaffected males. A previous meta-analysis (Honekopp & Watson, 2010) reported lower right hand (R2D:4D) and left hand (L2D:4D) digit ratios in patients with CAH relative to sex- matched controls. Our meta-analysis showed the same direction of results; however, the effects were only statistically significant for R2D:4D in males and L2D:4D in females (R2D:4D: females, p = 0.072, g = 0.591; males, p = 0.019, g = 0.513; L2D:4D: females, p = 0.020, g = 0.245; males, p = 0.334, g = 0.218), and the average effect size had reduced by 46.70%. We also found no evidence to suggest the right-left difference in 2D:4D (D[R-L]) is associated with prenatal sex hormone exposure.