Is the second to fourth digit ratio (2D:4D) a biomarker of sex-steroids activity?

The second-to-fourth digit ratio (2D:4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, and has been reported to be smaller in males than in females. This gender difference in digit length ratios has been linked with the in utero balance of androgens to oestrogen. This sexual dimorphism in 2D:4D ratios is apparent by 2 years of age and seems to be established early in life, possibly by the 14th week of gestation. Digits in females attain their maximum length at about 2.2 years (dextral subjects) or 5.1 years (sinistral subjects) earlier than those in males and increase slightly with age. It has also been reported that the 2D:4D ratio is correlated negatively with prenatal testosterone levels. This tentative theory is partially supported by lower 2D:4D in girls with congenital adrenal hyperplasia (CAH), higher 2D:4D in individuals with complete androgen insensitivity syndrome (CAIS) and a relationship between 2D:4D and polymorphisms in the androgen receptor. In contrast, individuals with Klinefelter syndrome (KS), who have reduced testosterone secretion throughout life, have a mean 2D:4D value similar to those found in female population norms. Nevertheless, its validity has not yet been conclusively demonstrated and is currently debated. In this context, our aim was to review and debate the relationship between 2D:4D ratio and sex-steroids activity in children, adolescents and young adults.