Beyond Hormones: Metabolic and Environmental Drivers (Kallistatin, Zearalenone) in Menstrual Regularity of Polycystic Ovary Syndrome
Abstract
Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrine disorder with diverse clinical manifestations, including menstrual irregularity. While its hormonal and metabolic aspects are well-studied, the combined effects of endogenous protective proteins like Kallistatin and environmental endocrine disruptors such as Zearalenone (ZEN) on menstrual regularity remain poorly understood. A cross-sectional study was conducted on 98 women diagnosed with PCOS using the Rotterdam criteria. Participants were classified into regular and irregular menstrual cycle groups based on clinical history. Serum levels of reproductive hormones, metabolic indices, Kallistatin, and ZEN were measured and compared between the groups. A p-value <0.05 was considered statistically significant. Women with irregular menstrual cycles exhibited more severe hormonal and metabolic disturbances. They had higher median testosterone (61 vs. 45 ng/dL) and lower SHBG levels (29 vs. 43 nmol/L). Metabolic indices also showed marked differences, with higher Visceral Adiposity Index (VAI: 4.2 vs. 2.4) and Lipid Accumulation Product (LAP: 119 vs. 94) in the irregular group. Notably, this group demonstrated significantly lower median Kallistatin levels (19 vs. 111 ng/mL) and higher ZEN levels (6.0 vs. 4.9 ng/L) compared to the regular-cycle group. The findings support the hypothesis that lower Kallistatin and elevated ZEN levels contribute to reproductive and metabolic dysfunction in PCOS.
References
H.J. Teede, M.L. Misso, and M.F. Costello, "Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome," Human Reproduction, vol. 33, no. 9, pp. 1602–1618, 2018. https://doi.org/10.1093/humrep/dey256.
R.L. Rosenfield and D.A. Ehrmann, "The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of functional ovarian hyperandrogenism," Journal of Clinical Endocrinology & Metabolism, vol. 107, no. 3, pp. 635–648, 2022. https://doi.org/10.1210/clinem/dgab807.
H. Rashid, X. Wang, Y. Li, "Environmental exposure to endocrine-disrupting mycotoxins and reproductive toxicity: Insights from recent studies," Toxins, vol. 13, no. 7, p. 450, 2021. https://doi.org/10.3390/toxins13070450.
X. Zhao, Y. Liu, J. Wang, "Zearalenone and its effects on reproductive health: A review of mechanisms and exposure risks," Toxins, vol. 14, no. 1, p. 58, 2022. https://doi.org/10.3390/toxins14010058.
W. Zhou, Y. Wang, Y. Li, et al., "Menstrual dysfunction and hormonal patterns in PCOS phenotypes: a cross-sectional analysis," Reproductive Biology and Endocrinology, vol. 21, no. 1, p. 45, 2023. https://doi.org/10.1186/s12958-023-01039-3.
Y. Wang, X. Zhang, J. Liu, et al., "Endocrine-disrupting potential of zearalenone in human granulosa cells and implications for fertility," Environment International, vol. 178, p. 107979, 2023. https://doi.org/10.1016/j.envint.2023.107979.
J. Chen, Y. Zhou, L. Zhang, "Kallistatin alleviates inflammation and oxidative stress in reproductive tissues: Potential therapeutic role in endocrine disorders," Cytokine, vol. 133, p. 155220, 2020. https://doi.org/10.1016/j.cyto.2020.155220.
R. Liu, Q. Song, L. Li, "Emerging roles of kallistatin in metabolic syndrome and its therapeutic potential," Frontiers in Endocrinology, vol. 13, p. 867493, 2022. https://doi.org/10.3389/fendo.2022.867493.
Q. Li, Y. Wang, Y. Liu, et al., "SHBG and bioavailable testosterone in PCOS: correlation with metabolic and reproductive parameters," Steroids, vol. 169, p. 108940, 2021. https://doi.org/10.1016/j.steroids.2021.108940.
F. Rashid, Y. Zhang, Y. Guo, et al., "Hormonal variations across PCOS phenotypes: environmental and genetic insights," Environmental Research, vol. 198, p. 112161, 2021. https://doi.org/10.1016/j.envres.2021.112161.
Y. Liu, F. Zhang, W. He, et al., "The clinical utility of lipid accumulation product in evaluating metabolic risk among PCOS patients," Molecular and Cellular Endocrinology, vol. 542, p. 111763, 2022. https://doi.org/10.1016/j.mce.2022.111763.
Y. Wang, L. Chen, Y. Zhao, X. Hu, "The role of visceral fat and metabolic dysfunction in PCOS phenotypes: a cross-sectional study," Reproductive Toxicology, vol. 112, pp. 45–52, 2023. https://doi.org/10.1016/j.reprotox.2023.107254.
Y. Zhao, Y. Liu, H. Xu, et al., "Altered kallistatin and inflammatory cytokines in PCOS: a biomarker study," Environment International, vol. 161, p. 107401, 2022. https://doi.org/10.1016/j.envint.2022.107401.
A. Yurtkal and M. Canday, "Kallistatin as a potential biomarker in polycystic ovary syndrome: A prospective cohort study," Diagnostics (Basel), vol. 14, no. 14, p. 1553, Jul. 2024.
F. Rashid, Y. Zhang, Y. Guo, et al., "Zearalenone exposure and hormonal disruption in reproductive-age women: evidence from PCOS phenotyping," Environmental Research, vol. 198, p. 112161, 2021. https://doi.org/10.1016/j.envres.2021.112161.
Q. Lv, W. Xu, F. Yang, W. Wei, X. Chen, Z. Zhang, and Y. Liu, "Reproductive Toxicity of Zearalenone and Its Molecular Mechanisms: A Review," Molecules, vol. 30, no. 3, p. 505, 2025. https://doi.org/10.3390/molecules30030505.
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