Abstract
The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: □ = -0.001 (−0.008, 0.006)]; females: □ = -0.004 [-0.015, 0.007]; males: □ = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.
Competing Interest Statement
M.E.G. receives consultant fees from Daiichi Sankyo, Ferring, Millendo Therapeutics, Novo Nordisk, Nutrition & Growth Solutions, Pfizer, Sandoz, and Tolmar; receives royalties from McGraw-Hill and UpToDate; and serves on data safety monitoring boards for Ascendis, Millendo, and Tolmar.
Footnotes
Reprint requests should be addressed to Gideon Nave
Funding Sources: This work was supported by funding support from the Abell Foundation to M.E.G. in the collection of the data and from the National Institutes of Health K23HD084735 (NIH/NICHD) to M.S.K. in the writing of the report. G.N thanks Carlos and Rosa de la Cruz for ongoing support.
Declaration of interests: M.E.G. receives consultant fees from Daiichi Sankyo, Ferring, Millendo Therapeutics, Novo Nordisk, Nutritional Growth Solutions, Pfizer, Sandoz, and Tolmar; receives royalties from McGraw-Hill and UpToDate; and serves on data safety monitoring boards for Ascendis, Millendo, and Tolmar.