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Context: Polycystic 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. Objective:we 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. Design &
Patients:The miRNA profile was assessed by RNA sequencingin 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
expressedmiRNAs were validated by qRT-PCR in the entire study population.
Post-treatment ovulation rates were assessed by salivary progesterone in
PCOS girls. Setting:Endocrinology Department, University Hospital
Results: Girls 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.
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