INS and polycystic ovary syndrome: In adolescents with PCOS and without obesity, a low-dose combination of one mixed antiandrogen and anti-mineralocorticoid (spironolactone) which increases brown adipose tissue activity (23, 28), and two insulin sensitizers (pioglitazone plus metformin) (spiomet) results in a better improvement in the metabolic condition as compared to OCs, including increased insulin sensitivity, reduced inflammation and liver fat accumulation, and more normalization of circulating hepatokines (20–23, 29).