The Intersection of Hepcidin and Polycystic Ovary Syndrome: A Review of Current Understanding

Abstract

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting up to 13% of reproductive-age women. It is characterized by a constellation of symptoms including menstrual irregularities, hyperandrogenism, and polycystic ovaries, often intertwined with metabolic disturbances such as insulin resistance and dyslipidemia. Hepcidin is a liver-produced peptide hormone that regulates iron homeostasis, with a significant role in the pathophysiology of PCOS. Hepcidin controls iron absorption and storage by binding to ferroportin, leading to its degradation and reducing iron export from enterocytes and macrophages. In PCOS patients, hepcidin dysregulation is linked to underlying hormonal and metabolic abnormalities, including insulin resistance and hyperandrogenism. Studies consistently demonstrate decreased hepcidin levels in PCOS patients, resulting in altered iron metabolism parameters, such as increased serum iron and ferritin concentrations, leading to iron overload. This iron overload can exacerbate complications like anemia. The relationship between hepcidin, anemia, and PCOS is influenced by several mechanisms. Hyperandrogenism in PCOS inhibits hepcidin synthesis, reducing iron sequestration and increasing serum iron levels, contributing to erythropoiesis and potentially mitigating anemia, while also posing a risk of iron overload. Hyperinsulinemia associated with insulin resistance further decreases hepcidin levels, enhancing dietary iron absorption and increasing serum iron levels. Despite the chronic low-grade inflammation typical in PCOS, which usually increases hepcidin levels, the inflammation may not be sufficient to override the suppressive effects of hyperandrogenism and hyperinsulinemia on hepcidin expression. Oligomenorrhea or amenorrhea in PCOS leads to reduced menstrual blood loss, contributing to iron retention and further influencing hepcidin regulation. Genetic and epigenetic factors also significantly impact hepcidin expression and iron metabolism in PCOS.