Exposure to multiple toxic metals and polycystic ovary syndrome risk: Endocrine disrupting effect from As, Pb and Ba

Polycystic ovarian syndrome (PCOS) affects 5 % ~ 20 % of women of reproductive age and is a serious health problem. Whether exposure to lead (Pb), mercury (Hg), arsenic (As), barium (Ba) or (cadmium) Cd is associated with an increased risk of PCOS, particularly their joint effect as well as their association with the clinical phenotype of PCOS is limited and unclear.

We aimed to explore the associations of the blood Pb, Hg, As, Ba and Cd levels and risk of PCOS in Chinese women of reproductive age.

A case-control study was used and included 369 women with PCOS and 441 controls. The levels of Pb, Hg, As, Ba and Cd were measured in fasting blood samples collected on the 2nd or 3rd day of menstruation or vaginal bleeding after drug withdrawal; basal sex hormone levels, fasting glucose and fasting insulin were measured simultaneously. Unconditional logistic regression models were used to assess the relationship of the blood Pb, Hg, As, Ba or Cd levels with PCOS risk. Bayesian kernel machine regression (BKMR) was used to assess the joint effect of Pb, Hg, As, Ba and Cd on PCOS risk and estimate which metal or metals contributed most to the association. Multiple linear regression models were used to investigate the relationships between the levels of selected metals and parameters of the clinical PCOS phenotype.

The mean ± SD ages of women in the case and control groups were 28.80 ± 3.39 and 28.97 ± 2.39 years, respectively; their mean ± SD BMIs were 23.86 ± 3.51 kg/m² and 22.08 ± 3.14 kg/m², respectively. The blood levels of three metals (Pb, As and Ba) were statistically associated with PCOS risk based on single-metal models. With each natural logarithm transformed (ln) unit increase in blood concentrations of Pb, higher likelihood of PCOS can be found, the adjusted odd ratio (aOR) and 95 % confidence interval (CI) was 1.83 (1.35-2.48), and these for As and Ba were 2.49 (1.86-3.33) and 1.20 (1.04-1.39), respectively. Compared with women at the first tertile group, higher likelihoods of PCOS among women in the second and third tertiles of the Pb group were observed, aORs and 95 % CIs were 1.81 (1.22-2.68) and 2.08 (1.42-3.04), respectively; and higher likelihoods of PCOS among women in the third tertiles of As and Ba group were also observed, the aORs and 95%CIs were 2.83 (1.93-4.15) and 1.89 (1.32-2.72), respectively. BKMR analysis also showed a statistically significant and positive joint effect of five metals on PCOS risk when the blood levels of five metals were all above the 55th percentile compared with their median levels, and As (100 %) and Pb (67.44 %) were the major contributors to the association. The blood As levels were positively associated with the luteinizing hormone (LH) levels and LH/FSH (follicle-stimulating hormone) ratio values, the blood Ba levels were negatively associated with the FSH levels, and the blood Pb levels were positively associated with the fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) values.

Our results suggest a positive association between exposure to multiple toxic metals (Pb, Hg, As, Ba and Cd) and PCOS risk. As and Pb were the major contributors, evaluated either as a single agent or metal mixture; and Pb, As, and Ba were associated with different parameters of the clinical PCOS phenotype. Additional studies are warranted to confirm these associations, particularly regarding the synergistic effect of toxic metals.