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. 2023 Jul 7;12(7):1398. doi: 10.3390/antiox12071398

Table 1.

Association of heavy metals and essential elements with oxidative stress in polycystic ovary syndrome (PCOS). Studies included in this systematic review. Statistically significant differences are presented.

Study, Year, (Country) Study Design Participants (No. of Women) Sample Type Exposure Main Conclusions
Köse et al. (2014), Turkey [55] Case–control study 20: 10 with PCOS (mean age: 24.0 ± 5.5), 10 controls (mean age: 27.8 ± 6.9) Peripheral whole blood sample Se
  • -

    Lower LP levels in PCOS + CPZ, PCOS + Se and PCOS + Se + CPZ groups

  • -

    Higher GPx activity and GSH level in PCOS + Se and PCOS + Se + CPZ groups

  • -

    Lower increase in Ca2+ in PCOS + Se and PCOS + Se + CPZ groups

  • -

    Lower increase in Ca2+ when exposed to CPZ and Se

  • -

    Greater effect of CPZ + Se on Ca2+ than CPZ
Guler et al. (2014), Turkey [56] Prospective study 86: 53 with PCOS (mean age: 25.4 ± 6.7), 33 controls (mean age: 28 ± 5.9) Overnight fasting venous blood sample Zn
  • -

    Lower mean Zn and homocysteine levels in PCOS

  • -

    Negative correlation of serum Zn with BMI and TG

  • -

    Serum Zn is the only significant and independent metabolic variable predicting PCOS

  • -

    Lower mean Zn levels in lean PCOS group compared to lean control group

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    Positive correlation between serum Zn level and modified Ferriman–Gallwey score
Jamilian et al. (2015), Iran [57] Randomized, double-blind, placebo-controlled study 48 with PCOS aged 18–40 Fasting blood sample Zn
  • -

    Decreased alopecia and hirsutism in Zn group

  • -

    Decreased MDA levels in Zn group

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    Higher TAC levels and lower 17-OH-P in Zn group after adjustment for baseline levels, BMI and age
Jamilian et al. (2015), Iran [58] Randomized, double-blind, placebo-controlled study 60 with PCOS aged 18–40 Fasting blood sample Cr
  • -

    Decreased hirsutism and acne in Cr group

  • -

    Decreased serum hs-CRP and plasma MDA levels in Cr group

  • -

    Higher TAC levels in Cr group

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    Lower PRL and NO levels and higher LH levels after adjustment for baseline levels of biochemical variables, BMI and age
Razavi et al. (2016), Iran [59] Randomized, double-blind, placebo-controlled study 64 with PCOS aged 18–40 Fasting blood sample Se
  • -

    Higher pregnancy rate in Se group

  • -

    Decreased alopecia, hirsutism and acne in Se group

  • -

    Decreased serum DHEA, serum hs-CRP and plasma MDA levels in Se group

  • -

    Lower FSH levels after adjustment for age and baseline BMI
Razavi et al. (2016), Iran [60] Randomized, double-blind, placebo-controlled study 60 vitamin D deficient with PCOS aged 18–40 Fasting blood sample Ca
  • -

    Decreased serum free T, DHEAS and plasma MDA levels in vitamin D-K-Ca group

  • -

    Increased plasma TAC levels in vitamin D-K-Ca group

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    Decreased LH and hs-CRP levels after adjustment for baseline values of biochemical parameters, age and baseline BMI
Özer et al. (2016), Turkey [61] Descriptive study 124 aged 20–30: 71 with PCOS, 53 controls Venous blood sample Zn, Cu
  • -

    Lower serum levels of Zn and CAT activity in PCOS group

  • -

    Higher MDA and GPx levels in PCOS group

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    Lower serum levels of Zn, CAT activity and MDA in GPx levels in PCOS group with IR (when compared to healthy controls)

  • -

    Lower serum Zn levels and CAT activity and higher MDA levels in PCOS group with IR (when compared to PCOS group without IR)

  • -

    Lower serum Zn levels and CAT activity and higher MDA and GPx levels in infertile PCOS group (when compared to healthy controls)

  • -

    Lower serum Zn levels and CAT activity and higher MDA levels in infertile PCOS group (when compared to fertile PCOS group)

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    Positive correlation between HOMA-IR and Zn levels
Ebrahimi et al. (2017), Iran [62] Randomized double-blind, placebo-controlled tri-al 60 with PCOS aged 18–40 Fasting blood sample Mg, Zn
  • -

    Decreased serum hs-CRP and protein carbonyl in Mg-Zn group

  • -

    Increased plasma TAC levels in Mg-Zn group

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    Downregulation of gene expression of IL-1 and TNF-α in peripheral blood mononuclear cells in Mg-Zn group
Jamilian et al. (2018), Iran [63] Randomized, double-blind, placebo-controlled study 40 infertile with PCOS, candidate for IVF, aged 18–40 Fasting blood sample Cr
  • -

    Decreased FBG, serum insulin, HOMA-IR, TG, VLDL and total cholesterol levels and increased QUICKI in Cr group

  • -

    Increased plasma TAC levels and decreased MDA levels in Cr group
Shokrpour et al. (2019), Iran [64] Randomized, double-blind, placebo-controlled study 60 with PCOS aged 18–40 Fasting blood sample Mg
  • -

    Reduced hirsutism and serum hs-CRP in Mg-vitamin E group

  • -

    Increased plasma NO and TAC in Mg-vitamin E group
Kanafchian et al. (2019), Iran [65] Case–control study 150 aged 20–40: 60 with PCOS, 90 controls Fasting venous blood Cu, Mg, Ca
  • -

    Higher serum Cu levels in PCOS group

  • -

    Negative correlation of serum Mg levels with HOMA-IR in PCOS group with IR

  • -

    Positive correlation of serum Mg levels with QUICKI in PCOS group with IR

  • -

    Negative correlation of serum Mg levels with TAC levels in PCOS group without IR

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    Positive correlation of serum Cu levels with BMI, TAC and G/I ratio in obese PCOS group

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    Positive correlation of serum Cu levels with G/I ratio and QUICKI in overweight PCOS group
Kirmizi et al. (2020), Turkey [66] Case–control study 154: 84 with PCOS (aged 22–36), 70 controls (aged 21–39) Blood sample As, Cr, Cd, Sb, Hg, Pb, Cu, Zn
  • -

    Higher plasma Sb, Cd, Pb and Hg levels in PCOS group

  • -

    Lower Zn and Cu levels in PCOS group

  • -

    Lower TAS, OSI and SOD values in PCOS group

  • -

    Higher TOS, MDA, hs-CRP and TNF-α levels in PCOS group

  • -

    Positive correlation between Cu and TAS in PCOS group

  • -

    Negative correlation between Zn and MDA, TNF-α and FBG in PCOS group

  • -

    Positive correlation between Sb and MDA, TNF-α, HOMA-IR and FBG; negative correlation with TAS, OSI and SOD in PCOS group

  • -

    Positive correlation between Cd and MDA, hs-CRP, BMI, HOMA-IR, FBG and insulin levels; negative correlation with TAS in PCOS group

  • -

    Positive correlation between Pb and FBG, MDA, TOS and hs-CRP; negative correlation with TAS, OSI and SOD in PCOS group

  • -

    Positive correlation between Cd, Hg, Pb and Sb and waist/hip ratio in PCOS group

  • -

    Higher Cd, Pb, TNF-α and hs-CRP levels in hirsutism group
Mousavi et al. (2021), Iran [67] Randomized, double-blind, placebo-controlled study 84 with PCOS aged 18–40 Blood sample Mg
  • -

    Decrease in weight, BMI, waist circumference, hirsutism and serum TNF-α levels in Mg-melatonin group

  • -

    Decrease in waist circumference in Mg group

  • -

    Increase in TAC levels in Mg-melatonin group
Abudawood (2021), Saudi Arabia [68] Prospective study 106 aged 19–35: 56 with PCOS, 50 controls Blood serum As, Cd, Pb, Hg
  • -

    Increased serum levels of As, Cd, Pb and Hg in PCOS group

  • -

    Negative correlation of As and Pb with SOD and GSH levels in PCOS group

  • -

    Negative correlation of Hg with GSH levels in PCOS women

  • -

    Positive correlation of As with increased Cd, Pb and Hg levels in PCOS group

  • -

    Significant correlations between Cd an Pb and between Cd and Hg

  • -

    Positive correlation of Hg with FBG and HbA1c in PCOS group

  • -

    Positive correlation of Cd with total cholesterol in PCOS group
Abudawood (2023), Saudi Arabia [69] Case–control study 106: 50 with PCOS (mean age: 30.41 ± 6.8), 56 controls (mean age: 29.16 ± 6.2) Blood serum Te, Tl, Sb, Os
  • -

    Increased levels of Te, Tl, Os and Sb in PCOS group

  • -

    Decreased serum TAC levels in PCOS group

  • -

    Positive correlation between Te levels and Tl, Os and Sb, and negative correlation with TAC levels in PCOS group

  • -

    Positive correlation between Tl and Sb, Sb and Os, and negative correlation between Tl, Sb, Os and TAC

Abbreviations: As, arsenic; BMI, body mass index; Ca, calcium; Ca2+, neutrophil intracellular calcium concentration; CAT, catalase; Cd, cadmium; CPZ, capsazepine; Cr, chromium; Cu, copper; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulphate; FBG, fasting blood glucose; FSH, follicle-stimulating hormone; G/I ratio, glucose/insulin ratio; GPx, glutathione peroxidase; GSH, reduced glutathione; HbA1c, glycated haemoglobin; Hg, mercury; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; hs-CRP, high sensitivity C-reactive protein; IL-1, interleukin-1; IR, insulin resistance; LH, luteinizing hormone; LP, neutrophil lipid peroxidation; MDA, malondialdehyde; Mg, magnesium; NO, nitric oxide; Os, osmium; OSI, oxidative stress index (TOS/TAS ratio); 17-OH-P, 17-hydroxyprogesterone; Pb, lead; PCOS, polycystic ovary syndrome; PRL, prolactin; Sb, antimony; Se, selenium; SHBG, sex hormone-binding globulin; SOD, superoxide dismutase; QUICKI, quantitative insulin sensitivity check index; T, testosterone; TAC, total antioxidant capacity; TAS, serum total antioxidant status; Te, tellurium; TG, triacylglycerols; Tl, thallium; TNF-α, tumour necrosis factor alpha; TOS, total oxidant status; VLDL, very-low-density lipoprotein; Zn, zinc.