PMID- 35926607
OWN - NLM
STAT- MEDLINE
DCOM- 20220929
LR  - 20220929
IS  - 1879-1026 (Electronic)
IS  - 0048-9697 (Linking)
VI  - 849
DP  - 2022 Nov 25
TI  - Exposure to multiple toxic metals and polycystic ovary syndrome risk: Endocrine 
      disrupting effect from As, Pb and Ba.
PG  - 157780
LID - S0048-9697(22)04879-3 [pii]
LID - 10.1016/j.scitotenv.2022.157780 [doi]
AB  - BACKGROUND: 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. 
      OBJECTIVES: 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. METHODS: 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. RESULTS: 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(2) and 22.08 +/- 3.14 
      kg/m(2), 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. CONCLUSIONS: 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.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Liang, Chunmei
AU  - Liang C
AD  - 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.
FAU - Zhang, Zhikang
AU  - Zhang Z
AD  - 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.
FAU - Cao, Yu
AU  - Cao Y
AD  - 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.
FAU - Wang, Jieyu
AU  - Wang J
AD  - 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.
FAU - Shen, Lingchao
AU  - Shen L
AD  - 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.
FAU - Jiang, Tingting
AU  - Jiang T
AD  - School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 
      230032, Anhui, China.
FAU - Li, Danyang
AU  - Li D
AD  - 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.
FAU - Zou, Weiwei
AU  - Zou W
AD  - 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.
FAU - Zong, Kai
AU  - Zong K
AD  - Technical Center of Hefei Customs District, No. 329 Tunxi Road, Hefei 230022, 
      Anhui, China.
FAU - Liang, Dan
AU  - Liang D
AD  - 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.
FAU - Xu, Xiaofeng
AU  - Xu X
AD  - 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.
FAU - Liu, Yajing
AU  - Liu Y
AD  - 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.
FAU - Tao, Fangbiao
AU  - Tao F
AD  - 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; School of Public Health, Anhui Medical University, 
      No. 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address: 
      fbtao@ahmu.edu.cn.
FAU - Luo, Guiying
AU  - Luo G
AD  - 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. Electronic address: 
      luogyhsz@126.com.
FAU - Ji, Dongmei
AU  - Ji D
AD  - 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. Electronic address: 
      cahsxjdm@aliyun.com.
FAU - Cao, Yunxia
AU  - Cao Y
AD  - 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. Electronic address: 
      caoyunxia5972@ahmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220802
PL  - Netherlands
TA  - Sci Total Environ
JT  - The Science of the total environment
JID - 0330500
RN  - 0 (Insulin)
RN  - 00BH33GNGH (Cadmium)
RN  - 24GP945V5T (Barium)
RN  - 2P299V784P (Lead)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - FXS1BY2PGL (Mercury)
RN  - IY9XDZ35W2 (Glucose)
RN  - N712M78A8G (Arsenic)
SB  - IM
MH  - *Arsenic
MH  - Barium
MH  - Bayes Theorem
MH  - Cadmium
MH  - Case-Control Studies
MH  - Female
MH  - Follicle Stimulating Hormone
MH  - Glucose
MH  - Humans
MH  - Insulin
MH  - Lead
MH  - Luteinizing Hormone
MH  - *Mercury
MH  - *Polycystic Ovary Syndrome/chemically induced/epidemiology
OTO - NOTNLM
OT  - BKMR model
OT  - Exposure
OT  - Polycystic ovary syndrome
OT  - Single metal model
OT  - Toxic metals
COIS- Declaration of competing interest No conflict of interest exists in the 
      submission of this manuscript, and the submission was approved by all the authors 
      listed.
EDAT- 2022/08/05 06:00
MHDA- 2022/09/30 06:00
CRDT- 2022/08/04 19:23
PHST- 2022/03/22 00:00 [received]
PHST- 2022/07/24 00:00 [revised]
PHST- 2022/07/29 00:00 [accepted]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/09/30 06:00 [medline]
PHST- 2022/08/04 19:23 [entrez]
AID - S0048-9697(22)04879-3 [pii]
AID - 10.1016/j.scitotenv.2022.157780 [doi]
PST - ppublish
SO  - Sci Total Environ. 2022 Nov 25;849:157780. doi: 10.1016/j.scitotenv.2022.157780. 
      Epub 2022 Aug 2.