In a previous study, we demonstrated that the concept of functional ovarian hyperandrogenism (FOH), as documented by the exaggerated 17OHP response to buserelin (GnRH-analogue) does not represent a specific feature of all women with PCOS, being present in less than half of PCOS and is a condition characterized by more severe hyperandrogenemia, glucose-stimulated B-cell insulin secretion and worse insulin resistance. INSL3 is produced in the Leydig cells and at reduced levels in ovarian thecal cells. We previously found that in PCOS serum INSL3 levels were significantly higher than controls and that in PCOS they were positively correlated with basal LH and 17OHP response to buserelin. We therefore carried out this study in two groups of PCOS characterized by normal (NR, n=6) or high (HR, n=6) 17OHP response to buserelin, and matched controls (n=44) to investigate whether INSL3 circulating levels may differ in PCOS subgroups, GnRH stimulation affects basal INSL3 concentration and whether a relationship exists between basal INSL3 levels and hormone response to buserelin. INSL3 concentratiosn were significantly higher in PCOS respect to controls (P=0.001). Moreover, in HR INSL3 levels were higher than in NR (P=0.006). Within PCOS the levels of INSL3 positively correlated with FAI (P=0.013) and negatively with SHBG (P=0.018). Moreover, a positive correlation with the % increase of LH after 60 min (P=0.037) and with the LHAUC after 60 min (P=0.014) and after 24 h (P=0.014) was found. Finally, INSL3 levels did not change after buserelin stimulation. These data confirm that PCOS women with FOH are more hyperandrogenic that those without it. Moreover, we have found that INSL3 levels may predict ovarian LH and androgen response to buserelin, which further suggests a potential role of INSL3 in the pathophysiology of hyperandrogenism in PCOS.
03 - 07 May 2008
European Society of Endocrinology