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BRIEF RESEARCH REPORT article

Front. Physiol.

Sec. Renal Physiology and Pathophysiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1653915

This article is part of the Research TopicBalancing Act: Exploring the Impact of Steroid Hormones, Diets/Supplements, and New Drugs on Renal FunctionView all 5 articles

Cross-Sex Hormone Therapy in rats induces sex-specific adaptations of renal function and Sodium Transporters expression

Provisionally accepted
  • 1Department of Physiology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, São Paulo, Brazil
  • 2Postgraduate Program in Translational Medicine, Department of Medicine, Universidade Federal de Sao Paulo Escola Paulista de Medicina, São Paulo, Brazil
  • 3Trans Care Outpatient Clinics; Núcleo de Estudos, Pesquisa, Extensão e Assistência à Pessoa Trans Professor Roberto Farina, Universidade Federal de Sao Paulo, São Paulo, Brazil
  • 4Laboratory of Molecular and Translational Endocrinology (LEMT), Endocrinology Division, Department of Medicine, Universidade Federal de Sao Paulo Escola Paulista de Medicina, São Paulo, Brazil

The final, formatted version of the article will be published soon.

Cross-sex hormone therapy (CHT) has been used in the gender identityaffirming process. Nevertheless, the literature about the renal repercussions of this therapy is scarce. Objective: Evaluate the effects of CHT on blood pressure (BP) and renal function. Methods: Male and female Wistar rats were distributed into groups: M+H (male+hormone), M+V (male+vehicle), F+H (female+hormone), and F+V (female+vehicle). CHT: M+H received algestoneacetophenide (3mg/kg) plus estradiol-enanthate (0.18mg/kg); F+H, testosterone-cypionate (3mg/kg). The vehicle was sesame oil. After 2 months of treatment, BP and renal function [inulin clearance (GFR), ions, and acid excretions] were evaluated. Sodium transporters expression (NHE3, NCC, α-ENaC, and β-ENaC) was assessed by immunohistochemistry. Results: Compared to M+V, M+H presented reduction in BP and GFR but increase in sodium and potassium excretion. GFR did not change in F+H, but sodium and potassium excretions were reduced. Ammonium excretion was decreased in M+H but increased in F+H. The NHE3 expression decreased in M+H and increased in F+H; females showed higher expression of NCC, while CHT did not change it. The β-EnaC expression was higher in females; CHT increased it in males and females. Conclusions: CHT induces sex-specific renal adaptations. Testosterone in females reduces the excretion of sodium and other ions, which may predispose to hypertension. Conversely, estradiol+algestone in males decrease the glomerular filtration rate and alter sodium handling, suggesting maladaptive responses. The expression of sodium transporters was altered in a sex-and nephron segment-specific manner. These findings highlight the need for further studies on the renal consequences of hormone therapy in transgender individuals.

Keywords: cross-sex hormone therapy, Renal function, Sodium transporters, Glomerular function, Blood Pressure

Received: 25 Jun 2025; Accepted: 04 Aug 2025.

Copyright: © 2025 Lichtenecker, Silva, Monteiro, Borges Da Mota Silveira, Argeri, Dias da Silva and Gomes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Guiomar Nascimento Gomes, Department of Physiology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, São Paulo, Brazil

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