# Skeletal effects of early pubertal suppression and peer-concordant puberty timing in transgender and gender diverse youth

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $169,020

## Abstract

PROJECT SUMMARY/ABSTRACT
 Transgender and gender diverse (TGD) youth initiate gender-affirming medical therapy as early as Tanner
Stage 2 with gonadotropin-releasing hormone agonists (GnRHa) for puberty suppression, with variable timing
of gender-affirming sex hormones (GAH). Peak bone mass, achieved during puberty and young adulthood,
largely determines age-related fractures in later life. There is compelling evidence that pre-treatment bone
mineral density (BMD) is low in TGD youth, and that peak bone mass attainment may be attenuated in
transfeminine youth. TGD youth who initiate GnRHa in early puberty develop bone geometry distinct from
those who start in late puberty. All published longitudinal studies on bone measures in TGD youth have
initiated GAH around 16 years (Dutch Model), and no studies have described skeletal trajectories of TGD
youth who initiate GnRHa in early puberty and follow a peer-concordant puberty-timing model with GAH by 14
years. The objective of this proposal is to evaluate the trajectory of bone mass, architecture, and
strength in TGD youth who follow the peer-concordant puberty-timing model, and to assess the
determinants of skeletal health in this population. Dr. Lee will enroll 30 participants from her existing cohort
of early pubertal TGD youth who have had detailed bone measures prior to and during the first year of GnRHa.
She will determine the skeletal measures during 3 years of GAH by utilizing dual-energy X-ray absorptiometry
(DXA) to quantify BMD accrual and BMD Z-score changes (Aim 1). Dr. Lee will correlate DXA measures to
high-resolution peripheral quantitative computed tomography (HR-pQCT) for bone architecture and strength
estimate changes at weight-bearing and non-weight-bearing sites, and at diaphyseal sites to examine muscle
mass and density (Aim 2). She found that low pre-treatment BMD in early pubertal TGD youth was associated
with low physical activity and that grip strength was a positive predictor of failure load. Dr. Lee will utilize thigh-
mounted tri-axial accelerometers to measure intensity/duration of physical activity/sedentary time and hand-
grip and knee extension dynamometry to measure isometric strength to develop threshold targets for future
intervention studies (Aim 3). Dr. Lee has assembled a cross-disciplinary mentor team with the necessary
expertise to achieve these aims and receive training in the endocrinology of bone and transgender medicine,
adolescent DXA and HR-pQCT interpretation, biomechanical load evaluation and muscle strength testing,
cohort study implementation, and complex longitudinal data analysis. The proposed research will generate
data for Dr. Lee to develop a larger R01 prospective study to follow skeletal trajectories until peak bone mass
attainment in order to optimize treatment protocols to mitigate potential impairment in peak bone mass accrual,
which could impact future fracture risk. Dr. Lee is committed to rigorous investigation of skeletal development
in ...

## Key facts

- **NIH application ID:** 10591361
- **Project number:** 1K23HD107265-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Janet Yi Man Lee
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $169,020
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10591361

## Citation

> US National Institutes of Health, RePORTER application 10591361, Skeletal effects of early pubertal suppression and peer-concordant puberty timing in transgender and gender diverse youth (1K23HD107265-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10591361. Licensed CC0.

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