Heavy Metals and Essential Elements in Association with Oxidative Stress in Women with Polycystic Ovary Syndrome Original paper

What was reviewed?

This systematic review synthesized findings from 15 human studies to evaluate the association between heavy metals, essential trace elements, and oxidative stress (OS) in women with polycystic ovary syndrome (PCOS). The review aimed to determine whether elevated toxic metal exposure and imbalances in essential micronutrients contribute to PCOS pathophysiology through mechanisms involving oxidative damage and inflammation. The authors used PubMed to identify literature from January 2008 to April 2023 and included studies that examined both heavy metals and essential elements in relation to markers of oxidative stress and metabolic and endocrine function in PCOS.

Who was reviewed?

The review encompassed studies involving women of reproductive age diagnosed with PCOS, compared to healthy controls. Across the 15 studies, sample sizes varied from small clinical trials to larger observational cohorts (up to 150 participants). The review focused on blood-based assessments (serum or plasma) of both toxic metals and essential elements, and linked these exposures to metabolic parameters, inflammatory biomarkers (e.g., hs-CRP, TNF-α), and OS markers (e.g., MDA, TAC, SOD, GSH).

What were the most important findings?

The review consistently found that women with PCOS exhibit elevated levels of heavy metals such as cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), antimony (Sb), tellurium (Te), thallium (Tl), and osmium (Os), while having significantly lower levels of essential elements like zinc (Zn), selenium (Se), and magnesium (Mg). The data reveal that these toxic metals are positively associated with markers of OS and inflammation, and negatively associated with antioxidant capacity. Specifically, Cd, Pb, and Sb levels were strongly correlated with higher fasting blood glucose, HOMA-IR, and pro-inflammatory markers, pointing to a direct metabolic and inflammatory insult. In contrast, supplementation with zinc, selenium, magnesium, and chromium showed protective effects, improving TAC levels, reducing oxidative stress markers, and lowering serum levels of androgens like DHEA and testosterone.

From a microbiome perspective, many of these toxicants, particularly cadmium and lead, are known to disrupt gut microbial balance by suppressing beneficial SCFA-producing bacteria such as Faecalibacterium prausnitzii and Bifidobacterium. This dysbiosis can fuel systemic inflammation and insulin resistance, exacerbating PCOS symptoms. Zinc and selenium support mucosal immunity and microbial diversity, and their deficiency may further impair gut barrier integrity and host–microbiome interactions.

What are the greatest implications of this review?

This review confirms that environmental exposure to heavy metals, alongside deficiencies in essential micronutrients, contributes to oxidative stress, inflammation, and metabolic dysfunction in PCOS. These findings underscore the importance of incorporating toxicological and nutritional evaluations into PCOS management. Clinically, there is a rationale for screening PCOS patients for metal burden and micronutrient status. Therapeutic strategies such as targeted supplementation (e.g., zinc, magnesium, selenium) or chelation, as well as dietary interventions to reduce toxicant exposure, may not only alleviate metabolic and endocrine symptoms but also support gut microbiome restoration. The integration of environmental health with endocrinology and microbiome research provides a promising, systems-level approach for improving outcomes in women with PCOS.