The role of steroid hormones in the sexual differentiation of the human brain.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing clinical, neuroimaging, and animal model literature without systematic search methodology
PubMed 34708466 · doi:10.1111/jne.13050
What was done
This narrative review synthesizes clinical, neuroimaging, and animal model evidence regarding steroid hormones and sex chromosomes in the sexual differentiation of the brain. It evaluates observational and neuroimaging data from individuals with altered androgen levels or actions, specifically congenital adrenal hyperplasia and complete androgen insensitivity syndrome (CAIS), and discusses gender incongruence.
What was found
The abstract reports no quantitative values or effect sizes. It qualitatively describes that prenatal androgens drive typical male neural and psychosexual differentiation in humans, with no apparent role for estrogens in masculinizing the human brain, contrasting with rodent models. Female neural characteristics are noted to potentially develop under prepubertal estradiol, while CAIS data suggest sex chromosome gene contributions, and gender incongruence is associated with altered sexual differentiation of the brain.
Why it matters
The review summarizes human neurodevelopmental endocrine mechanisms, emphasizing direct prenatal androgen action rather than estrogen-mediated aromatization in human brain masculinization.
Limits
The abstract provides no sample sizes, effect sizes, or quantitative data. As a narrative review, it lacks systematic search methodology. Human conclusions rely heavily on atypical endocrine models (CAH, CAIS), which may not fully generalize to typical population development.
Cited by
- supports The vast majority of individuals with complete androgen insensitivity syndrome identify as women and are sexually attracted to men.