Endometriosis Linked to Trace Element Imbalance and Oxidative Stress in New Study

Women with endometriosis show a distinctive pattern of altered blood chemistry, according to a new case-control study from Banaras Hindu University in Varanasi, India. In a cohort of 120 women, those with surgically or histopathologically confirmed endometriosis had significantly higher serum levels of arsenic, lead, mercury, copper, and iron, and significantly lower levels of zinc and selenium, than healthy fertile controls. These trace-element differences were accompanied by marked shifts in oxidative-stress biomarkers and inflammatory cytokines, painting a picture of what the researchers describe as an interconnected redox-inflammatory profile associated with the disease.

The study, published in Frontiers in Endocrinology, enrolled 60 women with endometriosis and 60 healthy controls between January 2024 and January 2025 at the Maternal and Child Health Centre of Sir Sunder Lal Hospital. All participants with endometriosis had laparoscopic or histopathological diagnoses and were staged using the revised American Society for Reproductive Medicine classification, with disease severity spread across stages I through IV. Roughly half of the cases fell into the moderate-to-severe category, ovarian endometrioma was present in 48 percent of patients, peritoneal lesions in 32 percent, and deep infiltrating endometriosis in 20 percent. Every woman with endometriosis in the cohort also presented with infertility, a detail that matters for interpreting the results.

The analytical approach combined two established laboratory techniques. Serum concentrations of eight trace elements—arsenic, lead, cadmium, mercury, copper, iron, zinc, and selenium—were measured using graphite furnace atomic absorption spectrophotometry with a direct dilution method, calibrated against certified standard reference solutions and quality-control measurements with coefficients of variation kept below five percent. Oxidative-stress biomarkers, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), along with six inflammatory cytokines, were quantified with enzyme-linked immunosorbent assays. Statistical comparisons were tailored to the data: trace elements and oxidative-stress markers, which showed non-normal distributions, were analyzed with the Mann-Whitney U test, while cytokine variables that met normality assumptions were compared using unpaired t-tests.

The trace-element results were striking in their breadth. Arsenic, lead, mercury, copper, and iron were all significantly elevated in the endometriosis group, with effect sizes ranging from moderate to large—lead showed the strongest separation, with an effect size of 0.57, while iron and selenium each reached 0.50. Zinc and selenium, both central to antioxidant defense, were significantly depleted in cases. Only cadmium failed to distinguish the groups, showing no statistically significant difference. Because zinc and selenium support antioxidant enzymes while toxic metals such as lead, mercury, and arsenic can increase oxidative and inflammatory burden, the pattern suggests a double burden: more pro-oxidant elements and fewer antioxidant ones.

The oxidative-stress measurements reinforced that interpretation. MDA, a marker of lipid peroxidation, was significantly higher in cases, as was 8-OHdG, which reflects oxidative damage to DNA. SOD, an enzymatic antioxidant, was also elevated—so much so that the effect size reached 0.86, the largest in the study. Glutathione, the cell’s principal non-enzymatic antioxidant, was significantly reduced. The authors suggest that the concurrent rise in SOD and fall in glutathione may reflect differential responses of enzymatic and non-enzymatic antioxidant defenses under oxidative stress, though they caution that all biomarkers were measured at a single time point.

Inflammatory profiling added a third layer. The cytokines TNF-α, IL-6, IL-1β, and IL-10 were all significantly elevated in the endometriosis group, while IFN-γ was significantly reduced. TGF-β trended higher in cases but did not reach statistical significance. The elevation of TNF-α, IL-1β, and IL-6 is consistent with the persistent inflammatory environment long described in endometriosis, and the researchers interpret the increased IL-10 as a possible compensatory anti-inflammatory response, though such interpretations remain speculative given the cross-sectional design.

Perhaps the most intriguing findings came from the correlation analysis, which the authors explicitly frame as exploratory. Within the endometriosis group, copper showed a moderate positive correlation with IL-1β, arsenic correlated positively with TGF-β, and iron showed a negative correlation with glutathione—consistent with the idea that higher iron burden accompanies depleted antioxidant capacity. Zinc was also positively correlated with TGF-β. Among the oxidative and inflammatory markers themselves, 8-OHdG correlated negatively with IL-10, hinting at a relationship between oxidative DNA damage and anti-inflammatory regulation. Notably, lead showed negative correlations with both MDA and TGF-β, a counterintuitive result the authors urge readers not to interpret as any protective effect of lead; they attribute it instead to complex biological regulation, differing exposure patterns, or residual confounding.

The study’s limitations are substantial and the authors are unusually candid about them. The endometriosis group was significantly younger than the controls (29.13 versus 32.40 years on average), and age can influence trace-element status, oxidative stress, and cytokine profiles, so residual confounding by age cannot be excluded. Because all cases had infertility while all controls were fertile, some biomarker differences may relate to infertility status rather than endometriosis itself—a selection bias the researchers acknowledge directly. Menstrual-cycle phase was not standardized, which matters because hormonal variation across the cycle can shift inflammatory and oxidative markers. Detailed dietary, occupational, and environmental exposure histories were not comprehensively quantified, even though such exposures strongly shape serum metal concentrations. The single-center design further limits generalizability.

Two methodological caveats deserve particular emphasis. First, the cross-sectional case-control design cannot determine whether the observed trace-element abnormalities contribute to the development of endometriosis or arise as a consequence of the disease process—no causal claims are possible. Second, no formal correction for multiple comparisons was applied to the correlation analysis, so the nominal p-values reported for the many pairwise associations should be treated as hypothesis-generating rather than confirmed findings, pending validation in independent cohorts. The authors also note that multivariable regression adjusting for age and fertility status was not performed.

What the study does establish is a detailed, internally consistent snapshot of systemic biological alterations in a well-characterized group of women with endometriosis. The coordinated pattern—elevated toxic and pro-oxidant elements, depleted antioxidant elements and glutathione, increased lipid peroxidation and DNA damage markers, and shifted cytokine levels—supports the concept of an integrated biomarker profile for characterizing the disease’s molecular landscape. The authors position these findings as hypothesis-generating evidence and call for larger multicenter and longitudinal studies, ideally with age-matched cohorts and comprehensive exposure assessment, to determine whether trace-element and oxidative-stress profiling can hold clinical relevance for endometriosis characterization or, eventually, care.

Subject of Research: Associations between serum trace elements, oxidative-stress biomarkers, and inflammatory cytokines in women with endometriosis

Article Title: Trace element imbalance and oxidative-inflammatory dysregulation in women with endometriosis

Article References: Ashish, A., Rai, S., Mishra, S., Maurya, A. K., Vishwakarma, S., Singh, N. K., Yadav, A. K., & Singh, R. (2026). Trace element imbalance and oxidative-inflammatory dysregulation in women with endometriosis. Frontiers in Endocrinology, 17, Article 1973603. https://doi.org/10.3389/fendo.2026.1973603

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1973603

Keywords: endometriosis, trace elements, oxidative stress, heavy metals, inflammation, cytokines, glutathione, arsenic, lead, zinc, selenium, case-control study