What is new in the landscape of insulin-sensitizing agents for polycystic ovary syndrome treatment.

Polycystic ovary syndrome, the most common gynecological endocrinopathy, is burdened with a state of hyperinsulinemia and insulin resistance in 50-80% of affected women. Wherever the origin of these metabolic abnormalities lies, their pathogenetic role in determining, perpetuating, and worsening the clinical traits of the syndrome is ascertained. Many studies have already highlighted possible mechanisms: hyperinsulinemia and insulin resistance may contribute to hyperandrogenemia, chronic anovulation, and other comorbidities of the syndrome by differentially affecting the endocrine glands (ovaries, adrenals, and pituitary) and peripheral tissues (fat mass and skeletal muscle). Based on these evidences, in the past years, thorough research has been focused on the possible role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Many compounds were tested to verify their efficacy against polycystic ovary syndrome-related metabolic dysfunction, both relying on previous acquired experiences in the field of diabetes mellitus and experimenting new agents, in particular, those belonging to the class of nutraceuticals. We sought to summarize the most relevant aspects of insulin-sensitizing treatments in polycystic ovary syndrome, by reporting the relevant literature on this topic and by keeping an attentive eye on the newly published international guidelines on polycystic ovary syndrome 2018. This overview encompasses metformin, thiazolidinediones, inositols, alpha-lipoic acid, and GLP1-R analogues. Starting from the analysis of the mechanisms of action, we anchored to the state of the art of the use of these drugs in polycystic ovary syndrome, to the most recent evidences for clinical practice and to the remaining open questions around indications, dose, treatment schedules, and side effects.