If high testosterone activity (especially relative to estrogen) is a risk factor for both sexes, both men and women with ASDs should have lower 2D:4D ratios. A mouse study also demonstrated that inactivation of androgen or estrogen receptors leads to higher or lower 2D:4D ratios, respectively. showed that the 2D:4D ratio of the right hand was negatively correlated with the ratio of testosterone to estrogen in amniotic fluid, indicating that individuals exposed to a higher testosterone:estrogen ratio tend to have lower 2D:4D ratios. The ratio is affected by both the amount of sex hormone exposure and sex hormone sensitivity. As an alternative indirect measure, the ratio of the second to fourth digit length (2D:4D) is frequently used to estimate prenatal sex hormone activity. However, it is unknown whether women with ASDs were exposed to high testosterone levels in utero.Īlthough measurement of amniotic fluid can be used to directly assess prenatal sex hormone exposure, the low prevalence of ASDs in women would require a large cohort study. Indeed, a recent study demonstrated that testosterone levels in the amniotic fluid samples of mothers of male babies later diagnosed with ASDs were elevated relative to those of TD male babies. Based on this hypothesis, excessive fetal testosterone exposure in men with ASDs causes “extreme male” cognition (superior systemizing and poorer empathizing) relative to TD men. This androgen exposure is thought to masculinize cognition, resulting in higher systemizing ability (i.e., understanding things as systems in terms of rules) and lower empathizing ability (i.e., understanding and responding to the mental states of others). In typically developing (TD) individuals, male fetuses are exposed to at least 2.5-fold higher levels of testosterone than female fetuses between weeks 8 and 24 of gestation. However, the etiology of ASDs in women is largely unknown.īaron-Cohen and colleagues proposed the extreme male brain (EMB) theory, in which the activities of sex hormones such as testosterone and estrogen during the prenatal period is one of the risk factors for ASDs. Based on such sex-biased prevalence ratios, a number of studies have investigated men-specific hormonal or genetic candidates for ASD risk factors. Previous studies have shown that the prevalence ratio for ASDs is four times greater in men than in women. Therefore, the present findings suggest that high prenatal testosterone could be a risk factor both for Japanese men and women with ASDs, elucidating one potential etiology of ASDs in women.Īutism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by difficulties in social communication and interaction and restricted, repetitive patterns of behavior, interests, or activities. However, a recent animal study showed that testosterone injection to dam leads to a higher right 2D:4D ratio especially for female offspring, which might be mediated by abnormal adipose accumulation in the fingertip. It has been posited that high prenatal testosterone levels lead to a lower 2D:4D ratio. We found a reverse direction of abnormality in the right 2D:4D ratio for men and women with ASDs. This group difference was not found for the left 2D:4D or right–left 2D:4D ratios. The higher right 2D:4D ratios in women could not be explained by age or full-scale intelligent quotients. No significant correlations were found between the 2D:4D ratios and the autism-spectrum quotient scores in any group. In contrast, the right 2D:4D ratios in women with ASDs were higher compared to those of TD women. In our cohort, men with ASDs tended to have lower right-hand 2D:4D ratios relative to TD men. We also examined the relationship between the 2D:4D ratio and the autism-spectrum quotient score of each group.

We measured digit lengths and compared the 2D:4D ratios among the four groups. The study included 35 Japanese men with ASDs, 17 Japanese women with ASDs, 59 typically developed (TD) Japanese men, and 57 TD Japanese women. Therefore, this study compared the 2D:4D ratios of women with and without ASDs to determine if prenatal sex hormone activity could be a risk factor for ASDs in women. The ratio of the length of the second to fourth digits (2D:4D) is considered to be a biomarker of the prenatal ratio of testosterone to estrogen. However, it is unclear whether prenatal sex hormone activity is a risk factor for women.

The extreme male brain theory proposes that excessive prenatal testosterone activity could be a risk factor for ASDs. The prevalence of autism spectrum disorders (ASDs) is higher in men than in women.

Higher 2d 4d ratio women