Endocrine Disruptors, Toxic and Essential Chemical Elements and Polycystic Ovary Syndrome

Endocrine disruptors are externally introduced chemical substances or mixtures of substances that, through altering hormone functions, cause unwanted effects on the health of an individual or its offspring or (sub)population. They are ubiquitous in the environment in polycarbonate plastic and plastic packaging (bisphenols) or in cosmetic and pharmaceutical products (parabens, triclosan). They enter the body through food and drinking water consumption, through inhaled air and contact with the skin. Studies have shown that EDs, especially bisphenols (e.g., bisphenol A-BPA, bisphenol S-BPS, bisphenol F-BPF), parabens and triclosan, through their impact on steroid receptors and epigenetic modifications, have a negative effect on women's reproductive health. Exposure to toxic and essential chemical elements can trigger the formation of reactive oxygen species, which affects steroidogenesis and metabolic processes.

The heterogeneity of the clinical picture in PCOS suggests that, in addition to genetic factors, environmental factors and lifestyle might also be involved in the etiopatoghenesis of the syndrome. Therefore, EDs are also the subject of research for a possible role in the development of PCOS. Some studies have confirmed elevated levels of BPA in the blood and urine of women with PCOS. The positive correlation of BPS with PCOS has been confirmed in only one study so far. The only study assessing blood levels of parabens in women with PCOS found no association with PCOS. So far, only two studies have examined the association of triclosan with PCOS, with conflicting results. Elevated levels of toxic chemical elements (e.g., Cd, Pb, Hg, As) and reduced levels of essential elements (e.g., Se, Zn) can also play a role in the development of PCOS. There are no studies assessing the role of Mo in PCOS. Since the current data on association of EDs and toxic and essential chemical elements with PCOS is scarce, the information obtained in our research could allow us to give an expert opinion on additional diagnostic tests and future recommendations on how to avoid the negative impact of EDs, toxic and essential chemical elements.

The research will be conducted at the Division of Obstetrics and Gynaecology, University Medical Centre Ljubljana, with the collaboration of the Clinical Research Centre, University Medical Centre Ljubljana, Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, and Jožef Stefan Institute. The study will be a prospective case-control study. The required number of samples was estimated based on one of the few published studies, where the presence of BPA was found in 95 % of PCOS women, while in the control group this proportion was 70 %. When analyzing the study power, we considered the standard values for alpha = 0.05 and a power of 80%. With these assumptions, we would need 35 women in each group. Women will be introduced to the study when treated for PCOS (study group) or attending the Division of Obstetrics and Gynaecology, University Medical Centre Ljubljana, for a regular periodic gynecological check-up (control group). After signing the informed consent form, clinical examination and transvaginal ultrasound with the antral follicle count will be performed. Each woman will fill in the questionnaire regarding her health status, fertility, pregnancies, deliveries, region of permanent residence, home and workplace environment, dietary and lifestyle habits, smoking and education. On the day 2 to 5 of regular menstrual cycle or after two or more months after last menstrual period in the case of oligo- or amenorrhea, fasting venous blood sample and first morning urine will be taken at the Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, for analysis of the content of bisphenols (BPA, BPS and BPF), parabens, triclosan, chemical elements (toxic - Cd, Pb, Hg and As, and essential - Se, Cu, Zn, Mn, Mo), blood count, liver and kidney function tests, Antimüllerian hormone-AMH, sex hormone binding globuline- SHBG and reproductive hormones (FSH, LH, PRL, TSH, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone sulfate). The analysis of EDs and chemical elements will be carried out at the Jožef Stefan Institute, while other diagnostic tests will be carried out at the Clinical Institute for Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, where the collection of biological samples will also take place. The protection of personal data will be guaranteed, as each blood sample will be labelled or recorded during the study under a code identical to the code of the questionnaire completed by the patient. The statistical evaluation of the data will be carried out at the University Medical Centre Ljubljana, Jožef Stefan Institute, and the Faculty of Medicine, University of Ljubljana. Appropriate statistical models, e.g., multiple linear regression, will be used to determine the relationship between EDs exposure, PCOS and lifestyle.