Serum trace elements and heavy metals in polycystic ovary syndrome Original paper

What was studied?

This clinical observational study evaluated the serum levels of essential trace elements in women with polycystic ovary syndrome (PCOS) compared to healthy controls. The research aimed to determine whether alterations in these micronutrients and toxic metals are associated with PCOS and its hormonal profile, particularly focusing on oxidative stress as a contributing mechanism. This was one of the earliest studies to analyze this specific combination of elements in PCOS patients using atomic absorption spectrophotometry.

Who was studied?

The study involved 35 women diagnosed with PCOS based on the Rotterdam criteria and 30 age- and BMI-matched healthy women serving as controls. All participants were of reproductive age and underwent thorough screening to exclude other endocrine disorders or confounding factors, such as medication use, thyroid dysfunction, or metabolic diseases. Blood samples were collected during the early follicular phase to standardize hormonal status, and serum levels of trace elements and hormones, including total testosterone and DHEAS, were measured using validated biochemical and spectrometric methods.

What were the most important findings?

Serum copper and zinc levels were significantly higher in the PCOS group, while manganese and lead levels were significantly lower. No significant differences were found in magnesium, cadmium, or cobalt concentrations between the two groups. Additionally, serum copper showed a strong negative correlation with BMI, while lead levels inversely correlated with total testosterone among PCOS patients—relationships not seen in the control group. Notably, although zinc levels were elevated in PCOS, they remained within the physiological range, whereas manganese levels in the PCOS group were approximately half those of the control group.

From a mechanistic standpoint, these findings align with the oxidative stress hypothesis of PCOS. Elevated copper can catalyze reactive oxygen species (ROS) formation and deplete intracellular glutathione, leading to mitochondrial dysfunction and inflammation. Zinc, while essential for antioxidant enzymes such as Cu/Zn superoxide dismutase (SOD), may reflect compensatory upregulation in response to inflammation. The reduced manganese levels suggest diminished activity of mitochondrial MnSOD, a critical antioxidant defense enzyme. Similarly, decreased lead levels, though surprising, may indicate redistribution or altered metabolic clearance. Each of these trace element imbalances can modulate the gut microbiome. Excess copper and zinc can suppress beneficial taxa like Bifidobacterium and Faecalibacterium prausnitzii, while manganese deficiency can impair the growth of SCFA-producing organisms that modulate inflammation and insulin signaling, features central to PCOS pathology.

What are the greatest implications of this study?

This study reinforces the hypothesis that PCOS is not only an endocrine and metabolic disorder but also a condition marked by trace element dysregulation and likely gut microbial imbalance. The observed elevations in serum copper and zinc, along with depleted manganese and altered lead levels, suggest that micronutrient homeostasis, particularly involving pro- and anti-oxidative pathways, plays a crucial role in the disease process. These findings highlight the need for clinicians to evaluate trace element status in PCOS patients as part of a broader strategy to manage oxidative stress and inflammation. Moreover, the trace elements measured may serve as noninvasive biomarkers for disease severity or subtyping and could inform targeted interventions involving dietary or supplemental modulation. Future studies should investigate the dynamic interactions between trace elements, microbiota composition, and hormone regulation, as well as whether correcting these imbalances improves metabolic, reproductive, and microbiome outcomes in PCOS.