Fetal Testosterone Hypothesis

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Fetal Testosterone and ASD


The Fetal Testosterone Hypothesis, which is also known as the Extreme Male Brain Hypothesis, says that factors during fetal life shape the brain as either a 'male' brain type or 'female' brain type. Male brains are more developed at "systemizing" while female brains are more developed at "empathizing." Systemizing refers to the ability to understand systems in terms of rules. This includes some traditional spatial tests and abstract mathematical systems, technical systems such as tools, natural systems such as the weather or biologic phylogenies, and structured social systems (e.g., dominance hierarchies). Empathizing includes appropriate emotional responding to another person but also includes the cognitive ability to model and predict people’s emotions, mental states, and behavior using a theory of mind and the ability to read people’s emotions and mental states in their face, voice, and body language. In this framework, autism occurs when an individual’s systemizing ability is intact or superior, whereas their empathizing ability is impaired.1


Some past studies supporting the fetal testosterone hypothesis used tests that did not correlate with fetal testosterone exposure indicators. One example is the Mental rotation test, where the subject is asked to compare two 3 Dimensional objects and state if they are the same images. Mental Rotation test is not ideal for testing elevated fetal Testosterone (fT). This is because mental rotation is not correlated with 2D:4D and girls with elevated exposure to fT as a result of congenital adrenal hyperplasia (CAH) are not faster or more accurate at mental rotation. Futhermore, researchers should distinguish between sex differences which arise from differences in neonatal testosterone and prenatal levels because no one has yet shown that the two are necessarily correlated.2

It is difficult to find any cognitive measure that is also a measure of fT exposure. If a cognitive task were to be used in this way, the focus should be on tasks where multiple different methodologies implicate fT, including studies of females with CAH, males with androgen insensitivity, correlations with digit ratio, and correlations with amniotic testosterone levels.Additionally, digit ratios should be used cautiously as a measure because there is evidence which suggests that ratios may not be stable in children and that there is a large variation with ethnicity. Additionally, there is the possibility that differences in digit ratio may be related to genes that are not affected by fetal testosterone.2

Tests for Fetal Testosterone theory

The effects of prenatal hormones on human sex differences have been difficult to study because it is clearly unethical to manipulate hormone levels in human fetuses. A role for fetal testosterone in human development is suggested by studies of the following:

  1. Individuals with disorders of sexual development
  2. Individuals who have been exposed to chemicals that mimic or block endogenous hormones
  3. Opposite-sex dizygotic twins
  4. Individuals whose fetal testosterone has been measured in umbilical cord blood
  5. Maternal testosterone levels during pregnancy
  6. Individuals whose fetal testosterone has been measured in fluid obtained at amniocentesis1

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1. Knickmeyer RC, Baron-Cohen S.Fetal testosterone and sex differences in typical social development and in autism. J Child Neurol. 2006 Oct;21(10):825-45. PMID 17005117

2. Knickmeyer RC, Baron-Cohen S, Auyeung B, Ashwin E.How to test the extreme male brain theory of autism in terms of foetal androgens? J Autism Dev Disord. 2008 May;38(5):995-6 PMID 18327635