Is prenatal testosterone-estrogen balance related to adolescent idiopathic scoliosis? A case-control study using...

Adolescent idiopathic scoliosis (AIS) exhibits a marked sexual dimorphism, with females up to ten times more likely than males to develop curves exceeding 30°, strongly implicating sex hormone signalling in its pathogenesis. The digit ratio (2D:4D), a marker of prenatal testosterone-estrogen balance, has been associated with several musculoskeletal conditions; however, its relationship with AIS has not been investigated.

We hypothesized that AIS patients would exhibit higher 2D:4D ratios indicative of relatively higher prenatal estrogen exposure, and aimed to evaluate the relationship between AIS and the 2D:4D ratio.

88 patients with AIS and 88 age- and sex-matched controls (mean age 14.9 ± 1.5 years; 78.4% female) were included. Second and fourth digit lengths were measured on both hands using a digital caliper. The 2D:4D ratio was calculated for each hand and compared between groups using the independent samples t-test and Mann-Whitney U test.

Both right and left 2D:4D ratios were significantly higher in the AIS group than controls (right:1.004 ± 0.032 vs. 0.960 ± 0.031, p < 0.001, Cohen's d = 1.40; left:1.003 ± 0.036 vs. 0.959 ± 0.030, p < 0.001, d = 1.33), consistent across both sexes. No significant correlation was found between 2D:4D and Cobb angle (right: r = 0.010, p = 0.929; left:r = -0.109, p = 0.350).

AIS patients exhibit significantly higher 2D:4D ratios than matched controls, suggesting that relatively high prenatal estrogen exposure may be associated with AIS development. The absence of correlation with Cobb angle indicates that prenatal hormonal balance may influence disease onset rather than curve severity. The 2D:4D ratio represents a potential biomarker for investigating prenatal hormonal influences in AIS.