Are Heavy Metal Exposure and Trace Element Levels Related to Metabolic and Endocrine Problems in Polycystic Ovary Syndrome? Original paper

What was studied?

This prospective clinical study investigated the relationship between serum levels of heavy metals and trace elements and their association with metabolic and endocrine parameters in women with polycystic ovary syndrome (PCOS). Specifically, the study evaluated arsenic, chromium, cadmium, lead, mercury, antimony (Sb), zinc (Zn), and copper (Cu), and how these elements influence oxidative stress, inflammation, insulin resistance, and clinical features like hirsutism in PCOS patients. The goal was to determine if exposure to toxic metals and altered micronutrient profiles could contribute to PCOS pathophysiology via oxidative and inflammatory pathways.

Who was studied?

The study involved 154 women, 84 diagnosed with PCOS according to the Rotterdam criteria and 70 age-matched healthy controls. All participants were screened to exclude confounding endocrine, metabolic, and inflammatory disorders. Clinical assessments included BMI, waist-hip ratio, Ferriman-Gallwey score (FGS) for hirsutism, and metabolic markers such as fasting glucose, insulin, HOMA-IR, and lipid profiles. Blood samples were analyzed for hormonal parameters, oxidative stress indicators (MDA, TOS, TAS, SOD, OSI), inflammatory markers (TNFα, HsCRP), and serum levels of heavy metals and trace elements using inductively coupled plasma mass spectrometry.

What were the most important findings?

Women with PCOS exhibited significantly elevated levels of cadmium, antimony, mercury, and lead, and significantly reduced serum levels of copper and zinc compared to controls. Importantly, the heavy metals cadmium, lead, and antimony positively correlated with fasting glucose and insulin resistance (HOMA-IR), as well as oxidative stress (MDA, TOS) and inflammation (TNFα, HsCRP), while showing negative correlations with antioxidant defense markers (TAS, SOD, OSI). Zinc and copper levels were significantly lower in the PCOS group and correlated with critical markers: zinc negatively with MDA and TNFα, and positively with TAS, suggesting a protective role against oxidative damage.

From a microbiome standpoint, the implications are striking. Elevated cadmium and lead promote gut dysbiosis by favoring inflammatory taxa such as Proteobacteria and reducing SCFA-producing genera like Faecalibacterium prausnitzii. Zinc deficiency suppresses beneficial microbes like Bifidobacterium, while lower copper levels impair mucosal immunity and reduce microbial diversity. These shifts likely exacerbate systemic inflammation and metabolic dysfunction in PCOS, further reinforcing the microbiome–trace element–endocrine axis.

What are the greatest implications of this study?

This study provides robust evidence that environmental heavy metal exposure and trace element imbalance contribute significantly to the oxidative stress and low-grade inflammation underlying PCOS. The data support the role of cadmium, antimony, and lead as endocrine disruptors and metabolic toxins that may worsen insulin resistance and hirsutism. In contrast, reduced zinc and copper levels reflect compromised antioxidant defense and immune regulation. Clinically, these findings justify the integration of trace element and toxic metal screening into PCOS diagnostics. Furthermore, targeted therapies, such as zinc supplementation, chelation strategies, or dietary interventions to limit metal exposure, may enhance treatment outcomes by reducing oxidative burden and restoring microbiome balance. This multifactorial view of PCOS, incorporating toxicology, endocrinology, and gut ecology, opens new opportunities for personalized care and prevention strategies.