Systemic dysregulation of essential and toxic elements and redox homeostasis in gynecologic malignancies

Endometrial cancer (EC) and ovarian cancer (OC) are among the most prevalent gynecologic malignancies, yet systemic biochemical alterations associated with these diseases remain incompletely characterized. Disturbances in essential and toxic element homeostasis, together with redox imbalance, have been implicated in cancer-related metabolic changes. This study aimed to comprehensively evaluate circulating macro- and trace elements alongside oxidative stress markers in women with EC and OC.

Serum and whole-blood concentrations of sodium (Na), potassium (K), calcium (Ca), phosphorus (P), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), and iron (Fe) were quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Systemic redox status was assessed by measuring total antioxidant status (TAS), total oxidant status (TOS), and calculating the oxidative stress index (OSI). Analyses were conducted in women with endometrial cancer stratified by tumor grade, patients with ovarian cancer stratified by treatment strategy, and corresponding control groups. Associations with age, body mass index, menopausal status, and type 2 diabetes were also evaluated.

In EC, higher tumor grade was associated with significantly lower circulating levels of Ca, Mg, and Fe, along with increased concentrations of Mn, Cu, Pb, and Cd. Decreasing trends were also observed for K and Zn. A comparable pattern was identified in OC, with the most pronounced alterations in patients requiring surgery followed by chemotherapy. Correlation analyses revealed significant inter-element relationships, particularly involving Mg, Cu, Pb, and Fe. Redox profiling demonstrated a progressive decrease in TAS and corresponding increases in TOS and OSI across tumor grades and clinical subgroups in both malignancies (p < 0.001 for all). Demographic and metabolic factors showed weak and inconsistent associations, with limited explanatory power of regression models.

Endometrial and ovarian cancers are associated with distinct yet partially overlapping alterations in systemic elemental composition and redox balance. These changes are stage-associated and may reflect complex, non-specific interactions between disease, host response, and environmental factors, although causality cannot be established. Combined multi-element and redox profiling may provide complementary insights into the systemic biochemical characteristics of gynecologic malignancies; however, further longitudinal and mechanistic studies are required to clarify their clinical relevance.