17 - Role of insulin sensitizers in the management of polycystic ovary syndrome

Abstract

Hyperinsulinemia and insulin resistance play a pivotal role in the pathophysiology of polycystic ovary syndrome (PCOS). In addition to lifestyle changes, insulin sensitizers have been used as a therapeutic option for the past few decades. Widespread use of insulin sensitizers in PCOS has brought a greater likelihood of more tangible clinical outcomes in terms of endocrine and metabolic dysfunctions, especially in obese females. Metformin is the only insulin-sensitizing agent that has shown promising results in patients with PCOS in terms of its combined metabolic and endocrine effects; however, its use in PCOS is off label. After lifestyle changes, it is the first-line insulin sensitizer in PCOS patients who have glucose intolerance or type 2 diabetes mellitus or who develop gestational diabetes. Metformin may improve fertility outcomes in patients with PCOS; however, it has not shown to be superior to clomiphene or letrozole in terms of ovulation induction and fertility outcomes. The other insulin sensitizer, thiazolidinedione, may improve endocrine and metabolic outcomes but can cause weight gain and should be avoided in those who wish to conceive. Inositol and alpha-lipoic acids (ALA) may improve insulin sensitivity, menstruation, and ovulation rate. Glucagon-like peptide-1 (GLP-1) agonists are incretins that result in weight loss, thus helping to improve insulin sensitivity, menstruation, and androgen levels. Evidence suggests that inositol, ALA, and GLP-1 agonists are mostly experimental and data show huge variations in terms of combination therapies, dose, and target subjects. Despite their promising clinical outcomes in a few studies, these agents are deemed to be experimental in patients with PCOS.