Low Circulating Levels of miR-451a in Girls with Polycystic Ovary Syndrome: Different Effects of Randomized Treatments.

Abstract

CONTEXT\nPolycystic ovary syndrome (PCOS) is a prevalent disorder in adolescent girls, purportedly driven by hepato-visceral fat excess, and often followed by subfertility and type 2 diabetes.\n\n\nOBJECTIVE\nwe studied the baseline miRNA profile of girls with PCOS, and the effects of a randomized treatment with an oral contraceptive (OC) or with spironolactone-pioglitazone-metformin (SPIOMET, aiming at loss of hepato-visceral fat excess) for 1 year.\n\n\nDESIGN & PATIENTS\nThe miRNA profile was assessed by RNA sequencing in girls with PCOS who had participated in a randomized, open-label, single-center, pilot study (n=31; age 15.7 years, BMI 23.1 Kg/m2). Healthy age- and BMI-matched girls (n=13) served as controls. Differentially expressed miRNAs were validated by qRT-PCR in the entire study population. Post-treatment ovulation rates were assessed by salivary progesterone in PCOS girls.\n\n\nSETTING\nEndocrinology Department, University Hospital.\n\n\nRESULTS\nGirls with PCOS -as compared to controls- had markedly reduced concentrations of circulating miR-451a, miR-652-3p, miR-106b-5p and miR-206; pathway enrichment analysis showed that these miRNAs target genes involved in energy homeostasis and cell-cycle control. In the present study, miR-451a could diagnose PCOS with 100% sensitivity and 100% specificity. SPIOMET (but not OC) was accompanied by on-treatment normalization of the miRNA profile in girls with PCOS; miR-451a concentrations after 1 year on OC or SPIOMET treatment associated closely (r=0.66; P<0.0001) with post-treatment ovulation rates. Conclusion: SPIOMET treatment for 1 year normalizes the miRNA profile of girls with PCOS. Circulating miR-451a may become a biomarker to guide the diagnosis and treatment of PCOS in adolescence.