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Updated: Aug 5, 2026
06:24
Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies
Published on: January 10, 2025
Beyond the Human Binary: Decoding Hormone-Immune Plasticity in Transgender Health
Giuseppa Cembalo1, Margherita Turrini1, Simone Baldi1
1Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Biology
|July 28, 2026
Summary
Gender-affirming hormone therapy reveals how hormones like testosterone and estradiol dynamically shape immune responses and microbial communities. This highlights the plasticity of human immunity beyond a simple male-female binary.
Area of Science:
- Endocrinology
- Immunology
- Reproductive Health
- Microbiome Research
Background:
- Traditional views of sex and gender differences in immunity often rely on a binary model.
- Endocrine signaling, particularly sex steroids, plays a dynamic role in immune function.
- Gender-affirming hormone therapy (GAHT) provides a model to study immune plasticity and sex steroid effects.
Purpose of the Study:
- To explore how estradiol and testosterone regulate immune set-points across various immune compartments.
- To investigate the interplay between hormonal signaling, cellular metabolism, and immune responses.
- To examine the impact of GAHT on mucosal barriers, reproductive microbiome, and associated health implications.
Main Methods:
- Review of existing evidence linking endocrine trajectories, immune function, and reproductive biology.
- Analysis of genomic and non-genomic signaling pathways of androgen and estrogen receptors.
- Examination of hormonal effects on cellular metabolism, including glutaminolysis and metabolome shifts.
- Assessment of GAHT's influence on vaginal and gut microbial communities and mucosal immunity.
Main Results:
- Testosterone dampens type I interferon responses and alters monocyte profiles; estradiol promotes macrophage polarization and T helper 1 responses.
- Androgen signaling acts as a metabolic brake on Th17 cells, influencing glutaminolysis and epigenetic remodeling.
- GAHT alters vaginal and gut microbial communities, impacting mucosal immunity and reproductive tract homeostasis.
- Hormonal context significantly influences immune set-points and plasticity.
Conclusions:
- Human immunity is highly responsive to endocrine context, demonstrating significant plasticity.
- GAHT offers insights into hormone-driven immune adaptation and its implications for reproductive health.
- A more inclusive framework is needed to understand human immune diversity, considering endocrine, environmental, and social factors.
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