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Background <p>Ferroptosis, a type of cell death driven by iron metabolism, has been implicated in polycystic ovary syndrome (PCOS), although the evidence remains conflicting. This study aimed to comprehensively investigate the relationship between PCOS and ferroptosis-related iron metabolism, with a particular focus on its contribution to ferroptosis.</p> Methods <p>We performed a systematic review and meta-analysis including clinical studies from PubMed, Embase, and Web of Science up to November 2024 to analyse and compare the levels of serum ferritin, iron, hepcidin, and transferrin saturation levels between women with PCOS and the controls. Additionally, a case-control study on serum ferritin levels and placental expression of ferroptosis-related genes was conducted in 16 pregnant women with a prepregnancy diagnosis of PCOS and 21 controls, at Women’s Hospital, School of Medicine, Zhejiang University, China, in 2022.</p> Results <p>Twenty-two studies were included, and significant differences in serum ferritin levels were found between women with PCOS and controls (standardized mean difference (SMD): 0.86; 95% confidence intervals (CI): 0.40 to 1.32; <i>P</i> &lt; 0.01). Moreover, serum iron (SMD: 0.46; 95% CI: 0.04 to 0.87; <i>P</i> = 0.03) and transferrin saturation (mean difference (MD): 4.85; 95% CI: 2.21 to 7.49; <i>P</i> &lt; 0.01) levels were significantly greater in women with PCOS, whereas serum hepcidin levels were lower (SMD: -2.09; 95% CI: -3.30 to -0.87; <i>P</i> &lt; 0.01). A case-control study revealed significantly elevated serum ferritin levels in the third trimester and notably upregulated expression of placental ferroptosis-related genes (ACSL4, TP53, GPX4, SLC7A11, and FTH1) at full term in the PCOS group compared with the control group.</p> Conclusion <p>Our findings highlight the involvement of ferroptosis-related dysregulation of iron metabolism in the pathophysiology of PCOS and suggest that altered placental ferroptosis is potentially linked to adverse pregnancy outcomes. Clinical health care providers should be more careful about decision-making concerning iron supplements for women with PCOS, especially pregnant individuals. Further work is needed to explore the regulatory mechanisms underlying iron metabolism in women with PCOS.</p> Clinical trial number <p>Not applicable.</p>

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Dysregulated iron metabolism related to ferroptosis in polycystic ovary syndrome: a meta-analysis and a case-control study in pregnant women

  • 期刊论文

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  • 发表日期：

    2025年11月28日

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  • Tianjing Wang,
  • Weihuan Hu,
  • Jue Zhou,
  • Leyi Fu,
  • Ningning Xie,
  • Feng Yun,
  • Jinlan Piao,
  • Jing Lin,
  • Danqing Chen,
  • Fan Qu,
  • Fangfang Wang

摘要

Background

Ferroptosis, a type of cell death driven by iron metabolism, has been implicated in polycystic ovary syndrome (PCOS), although the evidence remains conflicting. This study aimed to comprehensively investigate the relationship between PCOS and ferroptosis-related iron metabolism, with a particular focus on its contribution to ferroptosis.

Methods

We performed a systematic review and meta-analysis including clinical studies from PubMed, Embase, and Web of Science up to November 2024 to analyse and compare the levels of serum ferritin, iron, hepcidin, and transferrin saturation levels between women with PCOS and the controls. Additionally, a case-control study on serum ferritin levels and placental expression of ferroptosis-related genes was conducted in 16 pregnant women with a prepregnancy diagnosis of PCOS and 21 controls, at Women’s Hospital, School of Medicine, Zhejiang University, China, in 2022.

Results

Twenty-two studies were included, and significant differences in serum ferritin levels were found between women with PCOS and controls (standardized mean difference (SMD): 0.86; 95% confidence intervals (CI): 0.40 to 1.32; P < 0.01). Moreover, serum iron (SMD: 0.46; 95% CI: 0.04 to 0.87; P = 0.03) and transferrin saturation (mean difference (MD): 4.85; 95% CI: 2.21 to 7.49; P < 0.01) levels were significantly greater in women with PCOS, whereas serum hepcidin levels were lower (SMD: -2.09; 95% CI: -3.30 to -0.87; P < 0.01). A case-control study revealed significantly elevated serum ferritin levels in the third trimester and notably upregulated expression of placental ferroptosis-related genes (ACSL4, TP53, GPX4, SLC7A11, and FTH1) at full term in the PCOS group compared with the control group.

Conclusion

Our findings highlight the involvement of ferroptosis-related dysregulation of iron metabolism in the pathophysiology of PCOS and suggest that altered placental ferroptosis is potentially linked to adverse pregnancy outcomes. Clinical health care providers should be more careful about decision-making concerning iron supplements for women with PCOS, especially pregnant individuals. Further work is needed to explore the regulatory mechanisms underlying iron metabolism in women with PCOS.

Clinical trial number

Not applicable.