Huang-Doran I, Kinzer AB, Jimenez-Linan M, et al. - In the present study, the researchers sought to characterise hyperandrogenemia and ovarian pathology in primary severe insulin resistance (SIR), using insulin resistance of defined molecular etiology to interrogate disease mechanism, as well as to extend the evaluation of gonadotropin-releasing hormone (GnRH) analogue therapy in SIR. Participants in the study were female patients with SIR with documented serum total testosterone concentration. Whether due to proximal insulin signaling or adipose development defects, SIR induces severe hyperandrogenemia and polycystic ovary syndrome-like ovarian changes. Sex hormone binding globulin mediates a distinct relationship between IR and free testosterone between the groups. In a range of SIR subphenotypes, GnRH analogues are useful.