ORIGINAL RESEARCH article
Front. Med.
Sec. Obstetrics and Gynecology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1538368
This article is part of the Research TopicAdvancements in Diagnostic and Management Strategies for Gynecological PathologiesView all 18 articles
Exploring the Therapeutic Potential of H1-Antihistamines in Endometriosis: A Gene Regulation Perspective
Provisionally accepted
- 1University of Minnesota Twin Cities, Minneapolis, United States
- 2University of Missouri–Kansas City, Kansas City, Missouri, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Recent studies emphasize the role of immune dysregulation and inflammation in endometriosis (ES). While hormonal therapy remains the primary treatment, emerging research explores synergistic inflammation-targeting approaches. In this study, we investigate the potential of H1antihistamines (H1-As) in ES management from a gene-regulation viewpoint. We perform differential gene expression analysis on two gene-sequencing datasets from ES patients, primarily focusing on inflammatory signaling (NF-κB, TNF, Cytokine-Cytokine Receptor) and histamine synthesis/metabolism (HSM) pathways, with consideration of disease severity and hormonal therapy usage. Consistent with the literature, our findings highlight the dysregulation of several genes involving proinflammatory pathways such as Interleukins, COX-2, Chemokine Ligands, cellular adhesion molecules, neuroangiogenesis. We also note dysregulation of genes in the HSM pathway, indicative of a microenvironment that favors histamine availability and inflammatory persistence through enhanced histamine synthesis and reduced breakdown, and a reduced potential to clear reactive aldehyde species. We also find hormonal therapy minimally affects the dysregulation of most pro-inflammatory and histaminic pathway genes, and their amplified dysregulation is noted in early-stage disease. By putting our findings in the context of existing evidence on histamine-mediated modulation of inflammatory pathways via the H1 histamine receptor (HRH1), we present a comprehensive discussion on H1-As's potential therapeutic value in endometriosis management due to their anti-inflammatory, mast-cell stabilizing properties.
Keywords: Endometriosis, Endometrium, Gene Expression, Inflammation, H1-antihistamines
Received: 02 Dec 2024; Accepted: 12 Jun 2025.
Copyright: © 2025 Mantha and Gajendran. 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: Kameswara Bharadwaj Mantha, University of Minnesota Twin Cities, Minneapolis, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.