# Cross Sex Steroid Therapy and Cardiovascular Risk in the Transgender Female

> **NIH NIH F31** · UNIVERSITY OF MISSISSIPPI MED CTR · 2024 · $32,974

## Abstract

Transgender individuals comprise roughly 1% of the United States population and include those born one sex
but identify as a gender that does not align with their biological sex. Gender-Affirming Hormone Therapy (GAHT)
is used to treat these individuals to match secondary sex characteristics to their gender identity. GAHT in
transgender females (TGF), individuals born male but who identify as female, involves administration of 17β-
estradiol (E2) with an anti-androgen (AA) or castration (CTX). Although long-term studies in this population are
limited, recent studies suggest that cardiovascular (CV) risk may be elevated in GAHT-treated TGF versus cis-
gender men. However, the mechanisms involved are unknown and potential targets to ameliorate CV risk have
yet to be identified. To address this gap in knowledge, the Alexander laboratory has developed a novel model of
feminizing hormone therapy in the male rat that involves administration of E2 to mimic physiological levels
observed in age-matched female rats in conjunction with androgen suppression. My model mimics the increase
in E2, suppression of testosterone and decrease in body weight and lean mass observed in TGF individuals
indicating clinical relevance for this experimental model of GAHT. My studies will use two different rat strains,
the normotensive Sprague Dawley rat and the spontaneously hypertensive rat. Preexisting chronic disease such
as hypertension is contraindicated in GAHT. Yet, GAHT is integral for the treatment of gender dysphoria. To
date, basic research utilizing experimental models of GAHT are limited to nonexistent. Thus, a critical need
involves the use of innovative animal models to provide reliable risk assessment and in-depth investigation into
mechanisms that contribute to increased CV risk in adult TGF individuals that undergo GAHT. Therefore, my
F31 will test the following hypothesis that shifting the hormonal milieu with cross sex steroid treatment versus
natal sex, elevated estrogen coupled to testosterone suppression in the male, increases susceptibility to target
organ injury and cardiovascular risk that is enhanced with aging and involves an estrogen-induced male-specific
effect on the vasoconstrictor-vasodilator balance of the renin angiotensin system. Aim 1 will test the hypothesis
that the shift in the hormonal milieu in gender affirming hormone therapy in a rodent model of the transfemale
rat is associated with increased end organ damage and cardiovascular risk that is further exacerbated with
preexisting chronic disease. Aim 2 will test the hypothesis that increased end organ damage and cardiovascular
risk in transgender females that undergo gender affirming hormone therapy involves an estradiol induced “male
sex-specific” effect on the renin angiotensin system. This grant will also further my training potential as I learn
“gold-standard” methods for measurement of blood pressure via radiotelemetry, assessment of end organ
damage in response to myocardial is...

## Key facts

- **NIH application ID:** 10825268
- **Project number:** 1F31HL172648-01
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Breland Crudup
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $32,974
- **Award type:** 1
- **Project period:** 2023-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825268

## Citation

> US National Institutes of Health, RePORTER application 10825268, Cross Sex Steroid Therapy and Cardiovascular Risk in the Transgender Female (1F31HL172648-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10825268. Licensed CC0.

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