In-utero androgen exposure and 2nd to 4th digit length ratio-comparisons between healthy controls and females with classical congenital adrenal hyperplasia.

Abstract

Soft tissue measurements from the hand reveal lower second to fourth finger digit ratios (2D:4D) in males compared with females. The relatively longer 4th finger observed in males may be related to increased fetal exposure to androgens influencing the expression of Hox genes. We have measured 2D:4D ratios in 69 healthy females [median age 9.3 (range 1.9-17) years], 77 control males [median age 13.86 (2.1-20.3) years] and in 66 females with classical virilizing congenital adrenal hyperplasia (CAH) (median age 8.5 (1.1-16.2) years] who are known to be exposed to high concentrations of androgens in utero. Measurements were determined from X-rays of the left hand using vernier callipers. Intra-observer variability in measurement technique was 0.01%. Control males had a significantly lower mean (SD) 2D:4D ratio [0.918 (0.029)] compared with female patients [0.927 (0.029), ANOVA P = 0.02]. No difference in 2D:4D ratio was observed between CAH females [0.925 (0.021)] and control females [0.927 (0.029)]. In contrast, 2D:4D ratio in males were significantly lower compared with CAH females (P = 0.03). 2D:4D ratios determined directly from radiographs of the left hand confirm significant differences between males and females. However, female patients with virilizing CAH do not have a male digit ratio pattern suggesting that in the left hand digit ratio development is not influenced by in-utero exposure to androgens.