Low-Dose Spironolactone-Pioglitazone-Metformin Normalizes Circulating Fetuin-A Concentrations in Adolescent Girls with Polycystic Ovary Syndrome

Background. Fetuin-A is a glycoprotein produced in the liver and related to metabolic syndrome; fetuin-A secretion is divergently regulated in different pathological conditions. In girls with polycystic ovary syndrome (PCOS), insulin sensitization results in a more favorable endocrine-metabolic outcome than oral contraception; we assessed whether those differences are underscored by changes in circulating fetuin-A. Methods. Fetuin-A concentration endocrine-metabolic markers and hepatovisceral fat were measured longitudinally in 35 PCOS girls [age, 16 yr; body mass index (BMI), 23 kg/m2] randomized to receive either oral contraception [ethinylestradiol-levonorgestrel ( n=18 )] or a low-dose combination of spironolactone, pioglitazone, and metformin (SPIOMET, n=17 ) over 12 months. Healthy adolescent girls (age- and BMI-matched) were used as controls ( n=25 ). Results. Pretreatment fetuin-A serum levels in PCOS girls were lower than those in controls. After 12 months on treatment, fetuin-A raised to control levels only in the SPIOMET subgroup ( P=0.009 , versus oral contraception); this increase was paralleled by a healthier metabolic profile with less hepatic fat (by MRI); baseline serum fetuin-A as well as the changes over 12 months was inversely related to hepatic adiposity. Conclusions. A low-dose combination of insulin sensitizers and an antiandrogen—but not oral contraception—normalizes fetuin-A levels in adolescent girls with PCOS. This trial is registered with ISRCTN29234515 .