دراسة تأثير الزيرالينون والكاليستاتين في توازن الهرمونات الجنسية لدى مريضات متلازمة تكيس المبايض

Study the Effect of Zearalenone and Kallistatin in Sex Hormone Homeostasis among Patients with Polycystic Ovary Syndrome

Abstract

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder characterized by sex hormone imbalances, leading to reproductive and metabolic dysfunction. Though the primary drivers of hormonal dysregulation in PCOS are well-studied, the roles of emerging factors like environmental endocrine disruptors and novel endogenous proteins in sex hormone homeostasis are gaining attention. Zearalenone, a mycoestrogen, is known for its estrogenic activity, and Kallistatin, an adipokine, has roles in angiogenesis, inflammation, and metabolic regulation. Their potential influence on the intricate hormonal milieu of PCOS remains to be fully elucidated.
This study aimed to investigate the levels of Zearalenone and Kallistatin in women with PCOS and to explore their association with key sex hormone parameters, thereby shedding light on their potential impact on sex hormone homeostasis in this patient population.
A cross-sectional study was conducted from September 2024 to July 2025 in Iraq, recruiting 138 women from the Obstetrics and Gynecology Hospital in Karbala and Baghdad Teaching Hospital (Medical City). Included 98 patients diagnosed with Polycystic Ovary Syndrome (PCOS) and 40 apparently healthy women who served as a control group. Data were collected via a structured questionnaire covering sociodemographics, medical history, and lifestyle, complemented by clinical evaluations by specialist physicians.
Ninety-eight women aged 18-44 years were diagnosed with PCOS based on the 2012 Rotterdam consensus criteria: presence of at least two of three features: clinical/biochemical hyperandrogenism, oligo- or amenorrhea, and/or polycystic ovarian morphology (PCOM) via ultrasonography. Clinical hyperandrogenism was assessed by hirsutism (modified Ferriman–Gallwey score), acne, or androgenic alopecia, though biochemical hyperandrogenism involved elevated serum androgens. Menstrual irregularities included oligomenorrhea (>35-day cycles) or amenorrhea (<4-6 cycles/year). PCOM was defined as ovarian volume >10 mL and/or ≥12 follicles (2-9 mm). Patients were categorized into four phenotypes: Phenotype A: Anovulation (A), Hyperandrogenism (HA), Polycystic Ovaries (PCO), Phenotype B: A, HA without PCOM, Phenotype C: HA, PCO with ovulatory cycle and Phenotype D: A, PCO without HA
Detailed demographic and clinical data were collected, including anthropometric measurements (body weight, height, waist/hip circumference for BMI, BAI, VAI, LAP, BMR calculation), menstrual patterns, fertility status, and PCOS-related symptoms. Blood samples were analyzed for lipid profiles and reproductive hormones (FSH, LH, testosterone, E2).
Participants were excluded if they were pregnant or breastfeeding, had known endocrine disorders (e.g., thyroid dysfunction, hyperprolactinemia, congenital adrenal hyperplasia), diabetes mellitus, cardiovascular diseases, hepatic/renal dysfunction, autoimmune diseases, or were receiving corticosteroid therapy. These criteria aimed to minimize confounding factors and ensure a focused study population specific to PCOS.
This study investigated the levels of the mycoestrogen Zearalenone and the adipokine Kallistatin, alongside sex hormones and metabolic indices, in 98 Iraqi women with Polycystic Ovary Syndrome (PCOS) across various phenotypes (Rotterdam A, B, C, D), infertility types, and menstrual cycle regularities, comparing them to 40 healthy controls.
Results revealed significant hormonal and metabolic distinctions among PCOS subgroups. Patients with irregular menstrual cycles and classic hyperandrogenic phenotypes (A and B) exhibited higher testosterone and lower sex hormone-binding globulin (SHBG), coupled with elevated visceral adiposity index (VAI) and lipid accumulation product (LAP), indicating a more severe metabolic and hormonal profile.
Kallistatin levels were consistently and significantly lower in PCOS patients, particularly in those with irregular menstrual cycles and the more severe classic phenotypes (A, B, C), compared to healthy controls. Conversely, Kallistatin levels were notably higher in Normo-androgenic PCOS (Phenotype D), approaching those of healthy controls. ROC curve analysis demonstrated Kallistatin’s excellent discriminatory power for diagnosing Classic PCOS (Phenotype B: AUC 0.95; Phenotype A: AUC 0.88) and good power for Ovulatory PCOS (Phenotype C: AUC 0.83), but poor utility for Normo-androgenic PCOS (Phenotype D: AUC 0.64).
Zearalenone levels were generally similar or slightly elevated in PCOS patients versus controls, with the highest levels observed in the Un-married and irregular menstrual cycle groups, and notably in Normo-androgenic PCOS (Phenotype D). However, Zearalenone exhibited overall poor diagnostic discriminatory power across most phenotypes (AUCs 0.60-0.61 for A, B, C), showing only a modest diagnostic ability for Normo-androgenic PCOS (Phenotype D: AUC 0.75).
In conclusion, Kallistatin appears to be a strong potential diagnostic and characterizing biomarker for hyperandrogenic PCOS phenotypes, reflecting metabolic and ovulatory health. Zearalenone’s role is more nuanced, potentially acting as an environmental contributor in specific PCOS subgroups. These findings underscore the heterogeneous nature of PCOS and emphasize the importance of phenotype-specific biomarker evaluation for improved diagnosis and understanding of the disease.