Effects of adrenal androgens during the prenatal period on the second to fourth digit ratio in school-aged children

• 2D/4D was significantly lower in boys than in girls in school-aged children.
• Adrenal steroid hormones levels in cord blood related to sex differences in digits.
• 2D/4D negatively correlated with level of DHEA in cord blood in males.
• No correlations with 2D/4D were observed in the other adrenal steroid hormones.
• Sex differences in digits may be influenced by intracrinological processes.

ObjectivesWe investigated the relationship between the levels of adrenal steroid hormones in cord blood and the second to fourth digit ratio (2D/4D), which is regarded as an indirect method to investigate the putative effects of prenatal exposure to androgens, in school-aged children.Materials and methodsOf the 514 mother-child pairs who participated in the prospective cohort study of birth in Sapporo between 2002 and 2005, the following adrenal steroid hormone levels in 294 stored cord blood samples (135 males and 159 females) were measured; cortisol, cortisone, androstenedione and dehydroepiandrosterone (DHEA). A total of 190 out of 350 children who were currently school-aged and contactable for this survey sent back photocopies of their palms for 2D/4D measurements.Results2D/4D in all right hands, left hands, and mean values was significantly lower in males than in females (p < 0.01). DHEA levels were significantly higher in females. A multivariate regression model showed that 2D/4D negatively correlated with DHEA in males only (p < 0.01). No correlations were observed in the other adrenal steroid hormones tested in males or in any adrenal steroid hormones in females.ConclusionDHEA is mainly secreted in large amounts by the adrenal gland and is transformed into active sex-steroid hormones in peripheral tissues. The present study demonstrated that sex differences in digits were influenced by adrenal androgens during the prenatal period, possibly through intracrinological processes for androgen receptors located in fetal cartilaginous tissues.