# The effects of gender-affirming sex steroids on brain development in adolescents

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $800,403

## Abstract

Transgender and gender-nonbinary (TNB) adolescents may receive gender-affirming hormone therapy (GAHT)
with estradiol or testosterone to induce desired secondary sex characteristics, relieve gender dysphoria, and
improve mental health. Because GAHT is given during a crucial phase of brain development, many parents
and caregivers raise concerns about the potential effects of GAHT on brain development. Currently, the field
lacks empirical data on the effects of GAHT on brain structure and function in TNB adolescents. To address
this gap, we will conduct an observational, longitudinal study that will enroll 80 TNB adolescents (40
transfeminine and 40 transmasculine) who are starting GAHT as a part of their clinical care, and we will study
participants before and after 12 months of GAHT using state-of-the-art neuroimaging techniques. We will
specifically evaluate the structure and functional connectivity of the dorsolateral prefrontal cortex (DLPFC)
region of the brain, which is involved in regulating core executive functions, which are key determinants of
goal-directed behaviors, academic success, and personal autonomy. To account for normal age-related
changes in these neuroimaging outcomes, we will compare changes in our cohort to developmental changes
seen in cisgender adolescents from the general population using data from the Adolescent Brain and Cognitive
Development (ABCD) study, a prospective investigation of 11,878 children recruited nationwide that has made
data freely available to researchers. We will also investigate the association of neuroimaging changes in our
cohort with changes in the three core executive functions: response inhibition, cognitive flexibility, and working
memory. In addition, we will explore the correlations between changes in neuroimaging findings and changes
in symptoms of anxiety and depression. To account for changes in these neurocognitive and psychological
outcomes that occur normally with age, we have carefully selected measures that give scores that are
standardized for age. Our study will a) evaluate the effects of GAHT (estradiol and testosterone) on DLPFC
structure and function, and b) characterize the associations of GAHT-related changes with executive function
tasks and with symptoms of anxiety and depression. Our investigation will provide pragmatic data about the
effects of GAHT on brain changes in TNB adolescents and its relation to executive function to enable clinicians
to counsel patients and families about these effects and to eventually develop approaches to optimize
cognitive and educational outcomes.

## Key facts

- **NIH application ID:** 10944835
- **Project number:** 1R01HD115921-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** CHARU BASKARAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $800,403
- **Award type:** 1
- **Project period:** 2024-08-06 → 2025-03-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10944835

## Citation

> US National Institutes of Health, RePORTER application 10944835, The effects of gender-affirming sex steroids on brain development in adolescents (1R01HD115921-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10944835. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*