The role of circulating miRNAs in mechanism of action and prediction of therapeutic responses of metformin in polycystic ovarian syndrome
Abstract
OBJECTIVE
To study the involvement of microRNAs (miRNAs) in the pathogenesis of chronic anovulation and mechanism of metformin treatment in polycystic ovary syndrome (PCOS).
DESIGN
Case-control and prospective validation cohort study.
SETTING
Tertiary university hospital.
SUBJECTS
A total of 146 patients with PCOS and chronic anovulation and 20 non-PCOS controls were enrolled. Patients who resumed ovulation and remained anovulatory after metformin treatment were assigned to the MET-OV and MET-AO groups, respectively.
EXPOSURE
All patients with PCOS received metformin treatment for 6 months.
MAIN OUTCOME MEASURES
Baseline and chronological changes in the plasma levels of 14 miRNAs (miR-21, 93, 132, 193b, 221, 222, 223, 27a, 125b, 200b, 212, 320a, 429, and 483) selected by literature review, anthropometric data, and hormonal and metabolic profiles were measured. Predictive modeling based on baseline circulatory miRNA levels and clinical parameters was conducted to predict ovulation recovery after metformin treatment.
RESULTS
No significant differences were observed in the baseline hormonal and metabolic profiles between the MET-OV and MET-AO groups. However, the expression of miR-27a, miR-93, and miR-222 was significantly higher in the MET-OV group than that for the MET-AO (p=0.038, 0.03, and 0.012, respectively) and control (p<0.0001, 0.0003, and 0.0272, respectively) groups. After six months of metformin treatment, the levels of insulin, luteinizing hormone, and six…
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