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No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls

Lookup NU author(s): Dr Gareth RichardsORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


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 serial radiographs of the left hand obtained clinically in 91 youth with classical CAH (49.5% female) and 70 control youth (44.3% 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: 𝜷 = -0.001 (-0.008, 0.006)]; females: 𝜷 = -0.004 [-0.015, 0.007]; males: 𝜷 = 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.

Publication metadata

Author(s): Nave G, Koppin CM, Manfredi D, Richards G, Watson SJ, Geffner ME, Yong JE, Kim R, Ross HM, Serrano-Gonzalez M, Kim MS

Publication type: Article

Publication status: Published

Journal: Hormones and Behavior

Year: 2021

Volume: 128

Print publication date: 01/02/2021

Online publication date: 09/12/2020

Acceptance date: 23/11/2020

Date deposited: 26/11/2020

ISSN (print): 0018-506X

ISSN (electronic): 1095-6867

Publisher: Elsevier


DOI: 10.1101/2020.05.07.082529


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