Sex steroids, SHBG and type 2 diabetes in women: what do we really know?

Androgens and oestrogens differentially regulate metabolic processes that impact the development of type 2 diabetes in women. The biological actions of these sex steroids are, however, dependent on their bioavailability, which is regulated by their carrier protein sex hormone-binding globulin (SHBG). However, SHBG itself plays a role in the risk of developing type 2 diabetes, independent of the sex steroid. The molecular mechanisms underlying the effects of androgens, oestrogens and SHBG in the pathogenesis of type 2 diabetes in women are complex and multifaceted, spanning various insulin-sensitive tissues. This review explores the current knowledge on these topics and provides a mechanistic framework that integrates current experimental and clinical findings, providing insights into sex steroid-specific pathways and the sex steroid-independent effects of SHBG. Finally, the review highlights the need for further studies using appropriate models to delineate the relationship between androgens, 17β-oestradiol, SHBG and type 2 diabetes, with a view to translating these findings to improve women's health.