Endocrine Abstracts

Polycystic ovary syndrome is the most common cause of hirsutism & menstrual irregularity in adolescent girls. It is often accompanied by obesity and insulin resistance and associated to lifelong co-morbidities including reduced fertility, type 2 diabetes, premenopausal cancer, depression, and pregnancy and offspring complications. There is no approved therapy for PCOS in adolescent girls. Oral contraceptives (OCs) are prescribed off-label to approximately 98% of young PCOS patients, including to those without pregnancy risk. OCs do alleviate key symptoms, such as hirsutism and menstrual irregularity by inducing the pharmacological combination of anovulatory subfertility, regular pseudo-menses, and extreme elevations of sex hormone-binding globulin, but do not revert the underlying pathophysiology, and patients remain at risk for post-treatment subfertility. New insights suggest that PCOS is, in essence, the result of a mismatch between (less) prenatal weight gain and (more) postnatal weight gain, so that there is a chronic need to store more fat than is safely feasible in subcutaneous adipose tissue. The excess fat is stored in ectopic depots, especially in the liver and viscera. The extent of such storage is partly driven by genetic and epigenetic factors, and by a low brown adipose tissue (BAT) activity, contributing to a more positive energy balance. Given that PCOS appears to be commonly driven by hepato-visceral fat excess, the focus of the treatment should be a preferential loss of hepatic fat. This reduction can be achieved with a healthy lifestyle within a multidisciplinary approach. If these measures fail, then the addition of a medication mimicking the benefits of lifestyle intervention should be considered. Pilot studies have shown that SPIOMET, a low dose combination of spironolactone (to counteract androgen and mineralocorticoid effects and to raise BAT activity), pioglitazone (to raise circulating high-molecular-weight adiponectin), and metformin (to decrease appetite and improve insulin sensitivity) normalises more than OCs the PCOS phenotype, including ovulation rates and hepato-visceral fat excess. The efficacy and safety of lifestyle intervention plus SPIOMET will be further tested in a multi-centre, double-blind, randomised Phase II clinical trial (SPIOMET4HEALTH) in adolescent girls and young adult women with PCOS and funded by the European Commission.