# Understanding the effects of cross-sex hormone therapy on vaginal mucosal immunity

> **NIH NIH R21** · BOSTON MEDICAL CENTER · 2024 · $222,500

## Abstract

PROJECT SUMMARY/ABSTRACT
It is estimated that more than one million people in the United States identify as transgender. Despite recent
increased visibility, transgender individuals remain marginalized and subject to health disparities, and are
underrepresented in biomedical research. It is well documented that transgender persons are disproportionately
affected by HIV compared to their cisgender counterparts, but the basis for this is incompletely understood. In
particular, we have a very limited understanding of changes in mucosal immune defenses in the vaginal
compartment in transgender men and transmasculine individuals who receive chronic testosterone therapy as
part of gender affirming hormone therapy. This is relevant to understanding HIV risks as transgender men report
heterosexual, non-heterosexual, and bisexual orientation, making transgender men who have sex with cisgender
men a unique and understudied group. Our central hypothesis is that gender affirming hormone therapy in
transgender men leads to a dysregulated innate immune microenvironment and impaired barrier function of the
vaginal mucosal compartment, increasing the risk of HIV transmission during vaginal penetration. The goal of
this project is to characterize the effects of cross hormone therapy on the vaginal compartment using a
commercially available reconstructed vaginal tissue model that has been shown to be hormonally responsive
and support infection with HIV. We propose three aims to test our hypothesis. First, we will characterize the
histology of the testosterone dominant vagina in contrast to the estradiol primed vagina, looking at barrier
function, mucin expression, and steady state cytokine/chemokine release. The effects of testosterone on
colonization with lactobacillus will also be examined. Next, we will conduct transcriptomic studies to identify the
gene expression profile of the testosterone dominant vagina to identify changes in the immunologic signaling
pathways that could negatively impact host-pathogen interactions. Finally, we will examine HIV infection in the
testosterone dominant vagina in comparison to the estradiol primed vagina to determine if HIV transmission is
increased. At the completion of this project, we will have a broader understanding of the histologic and
immunologic effects of testosterone on the vaginal compartment, identifying defensive weaknesses in the
residual lower female genital tract in transgender men with an intact vagina that increase the risk of HIV
transmission. We believe our data will help inform the development of strategies for individuals undergoing
gender affirming hormone therapy to lessen the risk of HIV and other STI acquisition across this mucosal surface.

## Key facts

- **NIH application ID:** 10906956
- **Project number:** 5R21AI178913-02
- **Recipient organization:** BOSTON MEDICAL CENTER
- **Principal Investigator:** Robin R Ingalls
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $222,500
- **Award type:** 5
- **Project period:** 2023-08-14 → 2025-03-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906956

## Citation

> US National Institutes of Health, RePORTER application 10906956, Understanding the effects of cross-sex hormone therapy on vaginal mucosal immunity (5R21AI178913-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10906956. Licensed CC0.

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