Assessing the benefits of rosiglitazone in women with polycystic ovary syndrome through its effects on insulin-like growth factor 1, insulin-like growth factor-binding protein-3 and insulin resistance: a pilot study

Abstract

The physiopathology of insulin resistance in women with polycystic ovary syndrome (PCOS) is related to a disturbance in the function of the insulin receptor. In fact, the post-receptor defect associated with PCOS may be a critical factor that interferes with the recruitment of proteins for intracellular glucose transport. The conceivable end result is a compensatory increase in insulin (1). One possible option for correcting this insulin resistance is the use of drugs (such as metformin and glitazones) that may increase glucose intake in the tissue (1,2). However, there are studies showing that a few patients interrupted their metformin treatment due to a high incidence of gastrointestinal side effects, such as nausea or vomiting (2). Rosiglitazone binds to the peroxisome proliferator-activated receptor, which regulates the transcription of many genes, including the glucose transporter, and decreases insulin resistance (4); however, this drug may increase the risk of cardiovascular diseases, such as myocardial infarction. These effects are not reported in patients who have insulin resistance without diabetes (5). It is important to emphasize that endothelial damage is more pronounced in diabetic patients than in non-diabetic ones (6). Approximately 1% of IGF-1 circulates freely in the plasma; the remainder is transported by binding proteins. The efficacy of muscle IGF-1 depends on the expression and availability of a family of six types of binding proteins. In humans, the most important of these proteins is IGFBP-3 (>80%), which is responsible for the maintenance of the circulating IGF-1 levels, along with the ALS glycoprotein, which has great affinity for IGF-1 and -2 (7). The increase in insulin may affect IGF-1 actions. In fact, insulin decreases the production of IGFBP-3 in the liver. Therefore, the free levels of IGF-1 are elevated and may affect ovarian function and increase androgen production (8). The aim of this study was to evaluate the actions of rosiglitazone on IGF-1 and IGFBP-3 in women with PCOS.