Role of Decreased Circulating Hepcidin Concentrations in the Iron Excess of Women with the Polycystic Ovary Syndrome

Abstract

Hepcidin inhibits the intestinal absorption of iron and its deficiency causes juvenile hemochromatosis. The objective of the investigation was to study the involvement of hepcidin in the iron overload of patients with polycystic ovary syndrome (PCOS). This was a case-control study followed by a randomized clinical trial. The study was conducted at an academic hospital. Thirty-four patients with PCOS and 30 women without hyperandrogenism, matched for age and body mass index, participated in the study. Patients with PCOS were randomly allocated to treatment with either an antiandrogenic oral contraceptive or metformin for 24 wk. Serum hepcidin levels and ferritin to hepcidin molar ratios were measured. Patients with PCOS showed decreased circulating hepcidin levels and increased ferritin to hepcidin molar ratios compared with controls. Patients with PCOS presenting with chronic oligoamenorrhea (an iron sparing mechanism) showed a paradoxical decrease in serum hepcidin levels and an increase in ferritin to hepcidin molar ratios compared with the patients who had regular anovulatory menstrual cycles and with the controls. The major predictor of circulating hepcidin concentrations was the presence of PCOS, whereas the main determinants of the ferritin to hepcidin molar ratio were the insulin sensitivity index and menstrual dysfunction. Serum hepcidin levels did not change during treatment with either metformin or the antiandrogenic oral contraceptive pill, yet patients treated with the oral contraceptive pill normalized the ferritin to hepcidin molar ratio. Patients with PCOS had reduced serum hepcidin concentrations that might contribute to their iron overload by favoring the intestinal absorption of iron. The imbalance between increased iron stores and reduced hepcidin levels was related to the insulin resistance and androgen excess characteristic of this syndrome.