Hormones, context, and “brain gender”: a review of evidence from congenital adrenal hyperplasia
Abstract
Brain organization theory suggests that steroid hormones during fetal development permanently organize the brain for gender, including patterns of sexuality, cognition, temperament, and interests that differ by sex. This widely-accepted theory has important implications for health, ranging from medical management of infants with intersex conditions to suggested etiologies for sex differences in autism, depression, and other mental health problems. Studies of genetic females with congenital adrenal hyperplasia (CAH), in which high prenatal androgens have been linked to both atypical genitals and "masculine" patterns of gender and sexuality, are particularly important. Based on a comprehensive review of research on CAH, this article demonstrates that such studies have neglected four broad categories of variables that plausibly affect psychosexual development: (1) physiological effects of CAH, including complex disruption of steroid hormones from early development onwards; (2) intensive medical intervention and surveillance, which many women with CAH describe as traumatic; (3) direct effects of genital morphology on sexuality (versus indirect effects that "masculine" genitals may have on gender socialization); and (4) expectations of masculinization that likely affect both the development and evaluation of gender and sexuality in CAH. Complex and iterative interactions among postnatal biological variables, medical interventions, and social context provide a more plausible explanation for atypicalities in psychology and behavior that have been reported for genetic females with CAH than the conventional explanation that early androgens have "masculinized" their brains.
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Intravenous injections of AAVrh10-CAG-human CYP21A2-HA vector restored near-normal adrenal function; cells in the zona fasciculata but not the zona glomerulosa or capsule were efficiently transduced two weeks after a single AAV injection, with reduction of progesterone and ACTH levels.
“Intravenous injections of AAVrh10-CAG-human CYP21A2-HA vector endowed with adrenocortical tropism efficiently restored near-normal adrenal function; cells in the zona fasciculata, but not in the zona glomerulosa or capsule, were efficiently transduced two weeks after a single AAV injection, and this was concomitant with a reduction of progesterone and ACTH levels (519).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [519]
Restoration of proper steroidogenesis by AAV gene therapy was only transient.
“However, the restoration of proper steroidogenesis was only transient.”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [519]
Cites
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“The routine genital inspection at clinical visits “has been likened to sexual abuse” (Berenbaum, 2004; 8) and “women with CAH often remember childhood visits to their physician as highly intrusive” (Speiser et al., 2010; 4149).”
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Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
Claahsen - van der Grinten, H. L., Speiser, P. W., Ahmed, S. F., Arlt, W., Auchus, R. J., Falhammar, H., Flück, C. E., Guasti, L., Huebner, A., Kortmann, B. B. M., et al. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab016 · Cited by 556 · see citing works
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Characteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
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- Authors
- Jordan-Young, R. M.
- Affiliations
- Columbia University (US)
- Corresponding author
- Jordan-Young, Rebecca M.
- Venue
- Social Science & Medicine
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 74
- Issue
- 11
- Pages
- 1738-1744
- ISSN
- 0277-9536 (ISSN-L)
- OpenAlex
- W2092617949
- Cited by
- 79
- References
- 8
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 9 · 2013: 11 · 2012: 3
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Social Science & Medicine (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Robert Wood Johnson Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Social Sciences › Psychology › Social Psychology › LGBTQ Health, Identity, and Policy
- Social Sciences › Gender Studies › Gender and Feminist Studies
- Keywords
- congenital adrenal hyperplasia, prenatal androgens, sex differences, psychosexual development, gender development, medical surveillance, genital morphology, masculinization, intersex, autism spectrum disorder, depression, social environment
- MeSH terms
- Adrenal Hyperplasia, Congenital, Brain, Female, Hormones, Humans, Male, Models, Theoretical, Sexuality, Sexual Development
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