ESPE Abstracts

Introduction: Adolescent polycystic ovary syndrome (PCOS) is characterized by androgen excess and oligo-amenorrhea, and often results from ectopic lipid storage due to a mismatch between early adipogenesis and later lipogenesis. Endogenous HOTAIR and exogenous pioglitazone are enhancers of subcutaneous adipogenesis, particularly in the gluteofemoral region. The A allele of HOTAIR rs1443512 is an equivalent of a natural knock-down and is thus a candidate to influence the redistribution of fat by pioglitazone in adolescent PCOS.

Subjects & Methods: We performed a post hoc analysis – by HOTAIR rs1443512 genotype – of auxological, endocrine and body-composition results from 24 adolescent girls (mean age 15.6 years) with PCOS-without-obesity, all of whom received pioglitazone (7.5 mg/d for 1 year) as part of a randomised combination treatment (with spironolactone and metformin) in reported studies (ISRCTN29234515; ISRCTN11062950). All data had been obtained in a blinded-to-genotype way.

Results: The HOTAIR rs1443512 genotype in pioglitazone-treated girls did not detectably influence the measures of androgen excess, hyperinsulinaemia or abdominal fat (either subcutaneous, visceral or hepatic fat, by magnetic resonance imaging) but associated with differential – and even opposing – changes in other fat depots, so that girls with A allele of HOTAIR rs1443512 (n=12) gained fat while the other girls (n=12) did not: hip circumference (+2.3 ± 1.9 vs -1.7 ± 3.1 cm; P<0.001), total fat (by dual X-ray absorptiometry; +2.2 ± 1.8 vs -0.9 ± 2.2 kg; P<0.001), truncal fat (+0.8 ± 1.1 vs -1.2 ± 2.0 kg; P<0.01), gluteofemoral fat (+0.6 ± 0.4 vs -0.1 ± 0.5 kg; P<0.001) and leg fat (+1.2 ± 1.0 vs -0.05 ± 0.9 kg; P <0.01).

Conclusion: The redistribution of fat mass during prolonged low-dose pioglitazone treatment in adolescent girls with PCOS-without-obesity differed markedly by HOTAIR rs1443512 genotype. Early PCOS, in particular the variant presenting without obesity and with A allele of HOTAIR rs1443512, merits further testing as a candidate indication for low-dose pioglitazone from adolescence onwards, as to prevent complications such as diabetes in adulthood. Trial registration ISRCTN29234515; ISRCTN11062950