Liang Chunmei, Zhang Zhikang, Cao Yu, Wang Jieyu, Shen Lingchao, Jiang Tingting, Li Danyang, Zou Weiwei, Zong Kai, Liang Dan, Xu Xiaofeng, Liu Yajing, Tao Fangbiao, Luo Guiying, Ji Dongmei, Cao Yunxia
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Engineering Research Center of Biopreservation and Artificial Organs, No. 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Institute of Translational Medicine, No. 81 Meishan Road, Hefei 230032, Anhui, China.
School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China.
Sci Total Environ. 2022 Nov 25;849:157780. doi: 10.1016/j.scitotenv.2022.157780. Epub 2022 Aug 2.
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/m and 22.08 ± 3.14 kg/m, 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.
多囊卵巢综合征（PCOS）影响5%至20%的育龄女性，是一个严重的健康问题。接触铅（Pb）、汞（Hg）、砷（As）、钡（Ba）或镉（Cd）是否会增加患PCOS的风险，特别是它们的联合效应以及与PCOS临床表型的关联，目前尚不清楚且相关研究有限。
我们旨在探讨中国育龄女性血液中Pb、Hg、As、Ba和Cd水平与PCOS风险之间的关联。
采用病例对照研究，纳入369例PCOS女性和441例对照。在月经第2天或第3天或停药后阴道出血时采集的空腹血样中检测Pb、Hg、As、Ba和Cd的水平；同时测量基础性激素水平、空腹血糖和空腹胰岛素。使用无条件逻辑回归模型评估血液中Pb、Hg、As、Ba或Cd水平与PCOS风险的关系。采用贝叶斯核机器回归（BKMR）评估Pb、Hg、As、Ba和Cd对PCOS风险的联合效应，并估计哪种金属或哪些金属对该关联贡献最大。使用多元线性回归模型研究所选金属水平与PCOS临床表型参数之间的关系。
病例组和对照组女性的平均±标准差年龄分别为28.80±3.39岁和28.97±2.39岁；她们的平均±标准差体重指数分别为23.86±3.51kg/m²和22.08±3.14kg/m²。基于单金属模型，三种金属（Pb、As和Ba）的血液水平与PCOS风险在统计学上相关。血液中Pb浓度每增加一个自然对数转换（ln）单位，患PCOS的可能性就越高，调整后的比值比（aOR）和95%置信区间（CI）为1.83（1.35 - 2.48），As和Ba的分别为2.49（1.86 - 3.33）和1.20（1.04 - 1.39）。与第一三分位数组的女性相比，Pb组第二和第三三分位数组的女性患PCOS的可能性更高，aOR和95%CI分别为1.81（1.22 - 2.68）和2.08（1.42 - 3.04）；As和Ba组第三三分位数组的女性患PCOS的可能性也更高，aOR和95%CI分别为2.83（1.93 - 4.15）和1.89（1.32 - 2.72）。BKMR分析还表明，当五种金属的血液水平均高于其第55百分位数与其中位数水平相比时，五种金属对PCOS风险具有统计学上显著的正向联合效应，并且As（100%）和Pb（67.44%）是该关联的主要贡献者。血液中As水平与促黄体生成素（LH）水平和LH/FSH（促卵泡生成素）比值呈正相关，血液中Ba水平与FSH水平呈负相关，并与空腹胰岛素水平和胰岛素抵抗稳态模型评估（HOMA - IR）值呈正相关。
我们的研究结果表明，接触多种有毒金属（Pb、Hg、As、Ba和Cd）与PCOS风险之间存在正相关。As和Pb是主要贡献者，无论是作为单一物质还是金属混合物进行评估；并且Pb、As和Ba与PCOS临床表型的不同参数相关。需要进一步研究来证实这些关联，特别是关于有毒金属的协同效应。
