The prenatal sex steroid theory of autism after 25 years

We first proposed the prenatal sex steroid theory of autism 25 years ago in order to account for a number of then-unexplained observations around autism, including (1) why autism is diagnosed more often in males than in females; and (2) apparent ‘male-type’ shifts in cognitive traits associated with autism, such as empathising and systemising. Here we review 25 years of research testing this theory. Early studies found that higher prenatal testosterone levels were associated with slower social, language and empathy development, greater attention to detail, stronger systemizing, and more autistic traits. Subsequent studies suggested that both prenatal androgens and estrogens are associated with autism. New methods in genetics and using stem-cell-derived neural organoids have further indicated the importance of sex steroid hormones for neurodevelopment, as well as atypical patterns in autism. These new findings support and open new lines of research into the prenatal sex steroid theory of autism.