Fetuin-B as a biomarker for metformin response in women with polycystic ovary syndrome: a prospective study

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) (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p < 0.001), waist circumference (p < 0.001), and fatty liver index (FLI) (p < 0.001). At follow-up, the M-group showed greater improvements. Fetuin-B levels were significantly higher in the M-group at baseline (p = 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; p = 0.13). The M-group's fetuin-B levels decreased significantly (p < 0.001), while the C-group's levels increased slightly. Changes in fetuin-B levels differed significantly between groups (p < 0.001), and regression analysis confirmed a strong association (B: 1.80; 95% CIs: 0.57-3.03; p = 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.