Hofmann Konstantin, Singer Susanne, Meyer Ann-Christin, Theis Susanne, Hasenburg Annette, Brenner Walburgis, Skala Christine
Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Mainz, Germany.
King's Fertility, Fetal Medicine Research Institute, London, United Kingdom.
Front Med (Lausanne). 2025 Jun 25;12:1567255. doi: 10.3389/fmed.2025.1567255. eCollection 2025.
Polycystic ovary syndrome (PCOS), affecting 5-15% of women of reproductive age globally, is linked to metabolic complications such as insulin resistance, obesity, and non-alcoholic fatty liver disease. While metformin helps manage PCOS, reliable biomarkers for monitoring treatment response are lacking. Fetuin-B, a liver-derived protein, has emerged as a potential candidate, as previous studies have shown increased fetuin-B levels in women with PCOS. This study examined whether serum fetuin-B levels correlated with metabolic improvements in PCOS patients undergoing metformin therapy, exploring its potential as a biomarker.
PCOS patients from the Fertility Center at the University Medical Center Mainz were assigned to two groups: metformin therapy (M-group) and alternative/no treatment (C-group), based on their metabolic profiles. Baseline and 24-week follow-up assessments included gonadotropins and reproductive hormone levels, metabolic markers (such as lipid profile, hepatic markers, fasting and stimulated glucose levels, and the respective derived indices), and anthropometric data, including fetuin-B. A multivariate regression analysis evaluated associations between metabolic changes and fetuin-B levels.
A total of 62 PCOS patients were included (31 per group). At baseline, the M-group exhibited worse metabolic parameters compared to the C-group, including higher body mass index (BMI) ( < 0.001), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ( < 0.001), waist circumference ( < 0.001), and fatty liver index (FLI) ( < 0.001). At follow-up, the M-group showed greater improvements. Fetuin-B levels were significantly higher in the M-group at baseline ( = 0.01), but at follow-up, no significant difference was observed between the groups (M-group: 3.7mcg/mL; C-group: 4.4 mcg/mL; = 0.13). The M-group's fetuin-B levels decreased significantly ( < 0.001), while the C-group's levels increased slightly. Changes in fetuin-B levels differed significantly between groups ( < 0.001), and regression analysis confirmed a strong association (B: 1.80; 95% CIs: 0.57-3.03; = 0.01).
This study demonstrated that metformin therapy is associated with significantly reducing fetuin-B levels in PCOS patients, underscoring its role in enhancing metabolic health. These findings highlight fetuin-B as a potential biomarker for monitoring treatment efficacy, offering a link between metabolic and reproductive health.
多囊卵巢综合征（PCOS）影响着全球5%-15%的育龄女性，与胰岛素抵抗、肥胖和非酒精性脂肪肝病等代谢并发症相关。虽然二甲双胍有助于管理PCOS，但缺乏用于监测治疗反应的可靠生物标志物。胎球蛋白-B是一种肝脏衍生蛋白，已成为潜在候选物，因为先前的研究表明PCOS女性的胎球蛋白-B水平升高。本研究调查了接受二甲双胍治疗的PCOS患者血清胎球蛋白-B水平是否与代谢改善相关，探讨其作为生物标志物的潜力。
美因茨大学医学中心生育中心的PCOS患者根据其代谢状况被分为两组：二甲双胍治疗组（M组）和替代治疗/未治疗组（C组）。基线和24周随访评估包括促性腺激素和生殖激素水平、代谢标志物（如血脂谱、肝脏标志物、空腹和刺激后血糖水平以及各自衍生指标）以及人体测量数据，包括胎球蛋白-B。多变量回归分析评估代谢变化与胎球蛋白-B水平之间的关联。
共纳入62例PCOS患者（每组31例）。基线时，M组的代谢参数比C组更差，包括更高的体重指数（BMI）（<0.001）、胰岛素抵抗稳态模型评估（HOMA-IR）（<0.001）、腰围（<0.001）和脂肪肝指数（FLI）（<0.001）。随访时，M组显示出更大改善。M组基线时胎球蛋白-B水平显著更高（=0.01），但随访时，两组之间未观察到显著差异（M组：3.7mcg/mL；C组：4.4 mcg/mL；=0.13）。M组的胎球蛋白-B水平显著下降（<0.001），而C组的水平略有上升。两组之间胎球蛋白-B水平的变化差异显著（<0.001），回归分析证实存在强关联（B：1.80；95%置信区间：0.57-3.03；=0.01）。
本研究表明，二甲双胍治疗与显著降低PCOS患者的胎球蛋白-B水平相关，突出了其在促进代谢健康方面的作用。这些发现强调胎球蛋白-B作为监测治疗疗效的潜在生物标志物，为代谢和生殖健康之间提供了联系。
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