Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

Figure 1

The combined action of insulin-sensitizers on the liver and ovary and the supposed protecting effect on endocrine-related gynaecological cancer. In the liver metformin inhibits mitochondrial respiratory complex 1 promoting AMPK activation which improves the metabolic profile reducing hyperglycemia, hyperinsulinemia, and insulin resistance. Insulin-sensitizers have a positive effect in PCOS patients through normalization of hyperinsulinaemia that otherwise amplifies the excessive androgen production from the ovary theca cells via CYP17 phosphorylation and lower levels of SHBG. Metformin and inositols may play an anticancer role both as insulin-sensitizers and as aromatase inhibitors. Indeed, they improve metabolic profile, inhibiting the growth of tumoural cells stimulated by hyperinsulinemia, and normalize estrogen production, inhibiting the growth of estrogen-dependent cancers. OCT1: Organic Cation Transporter 1; LH: luteinizing hormone; ISF-1: insulin sensitivity factor; CYP17: Cytochrome P-45017; SHBG: sex hormone binding globulin; IGF-1: insulin-like growth factor; PCOS: polycystic ovary syndrome.