Introduction: Endocrine disruptors (EDs) and chemical elements (CEs) may play a role in the development of polycystic ovary syndrome (PCOS). However, few studies have investigated the associations between EDs and CEs and PCOS, and for certain substances—such as isobutylparaben (iBuP) and molybdenum (Mo)—research is lacking. The aim of this doctoral dissertation was to examine the associations between the levels of selected EDs bisphenols (bisphenol A-BPA, F-BPF, and S-BPS), parabens (methylparaben-MeP, ethylparaben-EtP, propylparaben-PrP, butylparaben-BuP, isobutylparaben-iBuP, and benzylparaben-BzP) and triclosan, and nine different CEs such as cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg), selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and molybdenum (Mo) in biological samples (whole blood, serum, urine) of participants with PCOS, along with liver and kidney function and lifestyle determinants, compared to healthy controls.
Methods: This case-control study was conducted between September 2020 and June 2024 at the Division of Obstetrics and Gynecology, University Medical Centre Ljubljana. The study included 70 participants (35 with PCOS and 35 in the control group), who underwent clinical and transvaginal ultrasound examination and completed a questionnaire on demographic and health data, lifestyle, environment (home and workplace), and diet. Fasting blood and urine samples were were immediately aliquoted into cryovials and stored (-80oC) at the Clinical Re-search Centre, University Medical Centre Ljubljana. Analysis for basic biochemical parameters and reproductive hormones using standard clinical chemistry methods was performed at the Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana. CE concentrations in urine, serum, and whole blood were determined at the Department of Environ-mental Sciences at Jožef Stefan Institute using inductively coupled plasma mass spectrometry (ICP-MS), while urinary ED concentrations were measured using gas chromatography coupled with triple quadrupole mass spectrometry (GC-MS/MS). Urinary CE and ED levels were normalized to specific gravity or creatinine. Data were analyzed using the Mann–Whitney U test and ANOVA, and Spearman correlation coefficients were calculated. Logistic regression mo-dels were adjusted for body mass index (BMI), age, and hematocrit (for blood CE concentrations that primarily bind to erythrocytes), and multiple linear regression models were also applied.
Results: Participants with PCOS had significantly higher BMI, androgen levels, and leukocyte counts compared to controls. They more frequently used vitamin and other dietary supplements. Concentrations of Mo in whole blood and serum were significantly lower in the PCOS group, while serum Cu concentrations were higher when compared to control group of participants. Urinary concentrations of EtP, BuP, and iBuP (normalized to creatinine) were significantly higher in PCOS participants than in control group of women. Changes in Mo (whole blo-od and serum), Cu (serum), and paraben (EtP, BuP, iBuP) concentrations in urine among participants with PCOS were associated with alterations in kidney function markers (urinary creatinine, urinary proteins), liver function markers (urinary urobilinogen, aspartate aminotransfera-se, alanine aminotransferase, urinary bilirubin), and gonadotropins (luteinizing hormone-LH and follicle stimulating hormone-FSH). Certain environmental and dietary factors in the PCOS group were associated with serum Cu (higher beef consumption) or lower serum Mo levels (consumption of pickled or processed vegetables); proximity to a landfill was inversely associated with Mo levels in whole blood and serum. The use of personal care products (facial clean-ser, lipstick, mineral powder, day cream) and household products (air fresheners) was associated with higher urinary paraben concentrations (EtP, BuP, iBuP) in participants with PCOS.
Conclusions: This study indicates potential associations between PCOS and Mo concentrations in serum and whole blood, Cu in serum, and urinary levels of EtP, BuP, and iBuP. Mo and Cu levels in biological samples may be associated with dietary habits, while paraben concentrations may be related to the use of personal care and household products. These findings suggest that PCOS should be considered not only as a pathological hormonal and metabolic condition but also in the context of environmental exposure to EDs and CEs, and lifestyle habits.
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