Iron Overload and Endometriosis: Mechanisms, Implications, and Therapeutic Targets Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Karen Pendergrass
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Karen Pendergrass
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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
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Endometriosis
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
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Endometriomas
Endometriomas
An endometrioma is a type of ovarian cyst filled with old blood, arising from endometrial tissue outside the uterus, typically causing pain and potentially impacting fertility.
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Infertility
Infertility
Infertility is the inability to conceive after 12 months of regular, unprotected sex. It affects both men and women and can be due to various physical, hormonal, or genetic factors. Treatments include medication, surgery, assisted reproductive technologies, and lifestyle changes.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Fact-checked by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What Was Reviewed?
This systematic review evaluated the role of iron in the pathophysiology of endometriosis. The review synthesized findings from 53 studies, including both human and animal research, to provide a comprehensive understanding of how excess iron contributes to oxidative stress, inflammation, and tissue damage in endometriosis. It also explored iron-related mechanisms such as ferroptosis and the implications for subfertility, symptom severity, and potential malignant transformation.
Who Was Reviewed?
The review included a total of 53 studies: 47 human studies involving 3,556 participants and 6 animal studies. The human studies primarily examined women diagnosed with endometriosis, and the included research utilized various bio-samples such as ovarian endometriomas, peritoneal fluid, and ectopic endometrial lesions. Animal studies focused on endometriosis models to explore systemic and local iron mechanics.
Key Findings
Iron overload is consistently found in endometriotic tissues and peritoneal fluid but not in systemic circulation. This localized iron accumulation stems from repeated bleeding within lesions, leading to oxidative stress and inflammation that perpetuates the ectopic growth of endometrial tissue. Dysregulated iron transport and the failure of homeostatic mechanisms contribute to this pathology, with increased expression of proteins such as divalent metal transporter-1 (DMT1) and decreased ferroportin expression in affected tissues.
Markers of oxidative stress, including lipid peroxidation and DNA damage, were significantly elevated in endometriotic lesions. Aberrant resistance to ferroptosis, an iron-dependent form of cell death, was identified as a key mechanism supporting lesion persistence. Additionally, iron-induced ferroptosis was linked to the production of pro-inflammatory and angiogenic factors like IL-8 and VEGFA, exacerbating inflammation and lesion vascularization.
Iron overload was implicated in subfertility, as higher iron concentrations in ovarian follicles and endometriomas were associated with impaired oocyte quality and development. These findings suggest that iron mechanics might influence folliculogenesis and embryo viability. Importantly, the review highlighted the therapeutic potential of iron chelators and ferroptosis modulators for managing endometriosis.
Implications of the Review
This review underscores the central role of aberrant iron metabolism in the pathogenesis of endometriosis, providing a mechanistic basis for its persistence, progression, and associated complications such as subfertility and chronic pain. Iron-related oxidative stress emerges as a critical driver of inflammation and tissue damage, making it a promising target for therapeutic intervention. Future research should explore the efficacy of iron-targeted treatments, such as chelators, and further elucidate the role of ferroptosis in endometriosis. These insights could lead to novel strategies for mitigating symptom severity and improving fertility outcomes in affected women.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Endometriomas
An endometrioma is a type of ovarian cyst filled with old blood, arising from endometrial tissue outside the uterus, typically causing pain and potentially impacting fertility.