Emerging mechanism-driven therapies for endometriosis: From GnRH antagonists to microbiome and device-based strategies (Review)

Thomas KS, Krupa Sara Thomas, Krupa Thomas, Subrahmaniyan Sujitha Lekshmi, Lekshmi SS, Subrahmaniyan Lekshmi, Gurrala Harshitha, Harshitha Gurrala, Gurrala H, Ramzan MR, Mohamed Ramzan, Mohamed Rayyan Ramzan, Ahmed Khalid Osman, Ahmed Osman, Osman AK, Sherin Z, Ziya Sherin
Medicine international · 2026 · vol. 6(6) , pp. 1–20 · doi:10.3892/mi.2026.341 · PMID:42923893 · W7214621016
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This review outlines emerging mechanism-driven therapies for endometriosis, including GnRH antagonists, microbiome treatments, and device-based strategies, while highlighting the need for rigorous trials to address evidence gaps.

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This review article examines emerging mechanism-driven therapeutic strategies for endometriosis, a chronic estrogen-driven condition characterized by pelvic pain and infertility. The authors discuss novel interventions such as GnRH antagonists, selective progesterone receptor modulators, anti-inflammatory agents, microbiome-based therapies, and device-based neuromodulation aimed at overcoming current treatment limitations like progesterone resistance. While these innovations offer promising alternatives to conventional hormone suppression and surgery, the paper notes that evidence is currently limited by small study sizes and significant disease heterogeneity. This paper is centrally about endometriosis — specifically reviewing new pharmacological, biological, and technological approaches to managing the disease.

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Abstract

Millions of women of reproductive age suffer from endometriosis, a chronic, estrogen-driven condition that causes pelvic pain, dysmenorrhea and infertility. Conventional therapy focuses on symptom suppression with hormone medications or the surgical excision of lesions; however, it is not curative. Recent developments in the understanding of the pathophysiology of endometriosis have revealed novel immunological and molecular mechanisms that are being used in experimental therapies. The present review outlines developing techniques, including targeted endocrine modulators, epigenetic treatments, anti-inflammatory and immunomodulatory drugs, antioxidants, anti-angiogenic medicines, and microbiome-based therapy. Prominent examples are new oral gonadotropin-releasing hormone receptor antagonists, selective progesterone receptor modulators and aromatase inhibitors that aim to overcome progesterone resistance. Alternative methods, such nutraceuticals and biologic and small-molecule inhibitors (such as metabolic drugs and anti-cytokine therapies) are being explored. Novel supplemental options are provided by device-based neuromodulation and improved surgical techniques (such as advanced laparoscopy, robotic excision, image-guided surgery, nerve-sparing techniques and adhesion barriers). While many of these innovations are promising, current evidence is limited by small studies and disease heterogeneity. Future directions emphasize rigorous trials with standardized outcomes, including fertility measures and combinations of therapies to achieve personalized, long-term relief.
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Print ISSN: 2754-3242 Online ISSN: 2754-1304 International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease. International Journal of Oncology is an international journal devoted to oncology research and cancer treatment. Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery. Oncology Reports is an international journal devoted to fundamental and applied research in Oncology. Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine. Oncology Letters is an international journal devoted to Experimental and Clinical Oncology. Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology. International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis. Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology. Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition. Publishes open-access research on using epigenetics to advance understanding and treatment of human disease. An International Open Access Journal Devoted to General Medicine. Review Open Access - Authors: - Article Number: 57|Published online on: September 28, 2026https://doi.org/10.3892/mi.2026.341 - Expand metrics + Millions of women of reproductive age suffer from endometriosis, a chronic, estrogen‑driven condition that causes pelvic pain, dysmenorrhea and infertility. Conventional therapy focuses on symptom suppression with hormone medications or the surgical excision of lesions; however, it is not curative. Recent developments in the understanding of the pathophysiology of endometriosis have revealed novel immunological and molecular mechanisms that are being used in experimental therapies. The present review outlines developing techniques, including targeted endocrine modulators, epigenetic treatments, anti‑inflammatory and immunomodulatory drugs, antioxidants, anti‑angiogenic medicines, and microbiome‑based therapy. Prominent examples are new oral gonadotropin‑releasing hormone receptor antagonists, selective progesterone receptor modulators and aromatase inhibitors that aim to overcome progesterone resistance. Alternative methods, such nutraceuticals and biologic and small‑molecule inhibitors (such as metabolic drugs and anti‑cytokine therapies) are being explored. Novel supplemental options are provided by device‑based neuromodulation and improved surgical techniques (such as advanced laparoscopy, robotic excision, image‑guided surgery, nerve‑sparing techniques and adhesion barriers). While many of these innovations are promising, current evidence is limited by small studies and disease heterogeneity. Future directions emphasize rigorous trials with standardized outcomes, including fertility measures and combinations of therapies to achieve personalized, long‑term relief. Copy and paste a formatted citation Spandidos Publications style Thomas KS, Lekshmi SS, Gurrala H, Ramzan MR, Osman AK and Sherin Z: Emerging mechanism‑driven therapies for endometriosis: From GnRH antagonists to microbiome and device‑based strategies (Review). Med Int 6: 57, 2026. APA Thomas, K.S., Lekshmi, S.S., Gurrala, H., Ramzan, M.R., Osman, A.K., & Sherin, Z. (2026). Emerging mechanism‑driven therapies for endometriosis: From GnRH antagonists to microbiome and device‑based strategies (Review). Medicine International, 6, 57. https://doi.org/10.3892/mi.2026.341 MLA Thomas, K. S., Lekshmi, S. S., Gurrala, H., Ramzan, M. R., Osman, A. K., Sherin, Z."Emerging mechanism‑driven therapies for endometriosis: From GnRH antagonists to microbiome and device‑based strategies (Review)". Medicine International 6.6 (2026): 57. Chicago Thomas, K. S., Lekshmi, S. S., Gurrala, H., Ramzan, M. R., Osman, A. K., Sherin, Z."Emerging mechanism‑driven therapies for endometriosis: From GnRH antagonists to microbiome and device‑based strategies (Review)". Medicine International 6, no. 6 (2026): 57. https://doi.org/10.3892/mi.2026.341

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