Hormonal and Metabolic Strategies to Overcome Insulin Resistance and Prevent Endometrial Cancer

Abstract

A role for insulin and its related protein IGF-1 as drivers of endometrial carcinogenesis is now well established, with epidemiological and in vitro evidence demonstrating insulin resistance to be critical to the development of the disease. In addition to a direct effect on the endometrium, stimulating unregulated cell proliferation, insulin also closely interacts with excess adipose tissue, increasing the aromatisation of androgens to oestrogen and decreasing the secretion of the adipokine adiponectin, a major regulator of insulin sensitivity. Interventions aimed at improving the body's response to insulin would, therefore, be expected to have a positive effect on preventing the development of endometrial cancer. Numerous lifestyle, pharmacological and surgical interventions have been shown to influence insulin resistance, either through weight loss, increased insulin secretion or modulation of signalling through the insulin receptor. This review discusses the mechanisms underpinning these strategies and, in particular, the existing data for their role in endometrial cancer prophylaxis.