ESPE Abstracts (2018) 89 RFC8.2

High Mobility Group Box 1 (HMGB1) is Increased in Adolescents with Polycystic Ovarian Syndrome (PCOS) and Decreases after Treatment with Myo-Inositol in Combination with [alpha]-Lipoic Acid (MYO+ALA)

Francesca Cirilloa, Cecilia Catellania, Gabriele Tridentia, Cristina Vezzania, Pietro Lazzeronia, Chiara Sartoria, Anna Maria Fulghesub, Simona Losia, Letizia Coradazzia, Sergio Amarria & Maria Elisabeth Streeta

aAzienda USL (Hospital) - IRCCS (Research Institute), Reggio Emilia, Italy; bUniversity of Cagliari, Cagliari, Italy

PCOS treatment in adolescence should aim at improving ovarian function, based on the pathophysiology of this condition. We previously described in cystic fibrosis and then in the PCOS an increase in HMGB1, secondary to reduced cystic fibrosis transmembrane conductance regulator (CFTR) expression in the ovary, associated with insulin resistance and inflammation that both characterize PCOS. Inositols and ALA derivatives are considered a good therapeutic option for their possible positive effects on insulin sensitivity, androgen reduction and ovulation rhythm. The aim of this study was to verify changes in HMGB1 serum concentrations in adolescents with PCOS treated with MYO+ALA, in addition metabolic and other endocrine values were evaluated also. Twenty-five adolescents (CA: 16.46±0.57 years; BMISDS: 1.07±0.24; hirsute N.19; with amenorrhea: N.6; with oligomenorrhea: N.11; regular cycles: N.8) affected by PCOS (Rotterdam criteria) and 15 controls matched for age and BMI (CA: 18.18 10; ±0.84 years; BMISDS: 0.4±0.36) all with a gynecological age of at least 2 years were enrolled. In all subjects glycemia, insulin, hepatic and renal function, TSH, PRL, LH, FSH, E2, progesterone, 17-OHP, delta-4-androstenedione, total testosterone, triglycerides, total and fractional cholesterol, IGF-I, and uric acid were assayed. HOMA-IR and the TG/HDL-C ratio were calculated. Waist circumference (WC) and the WC/height ratio were measured. Ovarian and uterine volumes, number of follicles/ovary, uterus body/neck ratio, and uterus volume were evaluated by pelvic ultrasound. Patients were treated with MYO+ALA for 3 months twice a day and for further 3 months, once a day. HMGB1 was assayed using a specific ELISA kit (SHINO-TEST). Statistical analysis was performed using SPSS v23.0. HMGB1 was increased in PCOS compared with controls (18.63±5.12 vs 4.51±1.10 ng/ml; P <0.005). HMGB1, in PCOS, correlated with E2 (r=−0.40; P=0.04), total testosterone (r=−0.41; P=0.05), IGF-I (r=−0.48; P=0.04), and marginally with TG/HDL (r=−0.43; P=0.057). After 6 months therapy, HMGB1 decreased to 3.14±0.74 ng/ml, similar to concentrations measured in controls. Treatment reduced also, although not significantly, the HOMA-IR index, FSH and 17-OHP. No other changes were detected. Circulating HMGB1 is increased in PCOS adolescents, correlates with some parameters of ovarian function and IGF-I. MYO+ALA treatment was effective over a 6 month period in normalizing HMGB1, likely reducing inflammation and improving insulin sensitivity.