DOI: 10.1530/EJE-07-0801
European Journal of Endocrinology, Vol 158, Issue 3, 439
Copyright © 2008 by European Society of Endocrinology
Does metformin improve polycystic ovary syndrome symptoms through reduction in body iron stores?
Luca Mascitelli and
Francesca Pezzetta1
<?A3B2 twb=.31w>Sanitary Service, Comando Brigata alpina ‘Julia’, Udine 33100, Italy and 1 Cardiology Service, Ospedale di San Vito al Tagliamento, San Vito al Tagliamento 33078, Italy
(Correspondence should be addressed to L Mascitelli; Email: lumasci{at}libero.it)
To The Editor – Tan et al. (1) found that metformin improved polycystic ovary syndrome (PCOS) symptoms irrespective of pretreatment insulin resistance or obesity. However, the mechanisms underlying this association are not clearly understood. We suggest that some of the involved mechanisms might be related to the reduction in body iron stores induced by metformin. Indeed, it has recently been found that metformin, increasing insulin sensitivity, may decrease intestinal iron absorption in patients with PCOS (2).
Mounting evidence indicates that higher body iron stores are associated with an increased risk of other insulin-resistant disorders such as type 2 diabetes (3). In fact, it has been demonstrated that increased iron stores may contribute to insulin resistance by reducing hepatic insulin extraction and metabolism (4), and by decreasing glucose uptake in muscle (5). On the other hand, induction of near-iron deficiency in carbohydrate-intolerant subjects has been shown to improve insulin sensitivity (6). Furthermore, a small intervention study in patients with type 2 diabetes and elevated ferritin levels showed that bloodletting, which resulted in a 50% reduction in serum ferritin concentrations, improved glycemia and insulin sensitivity (7).
Therefore, metformin-induced reduction in body iron stores may break the vicious circle of reduced insulin sensitivity, increased intestinal iron absorption, and further worsening of insulin sensitivity (2), thus improving symptoms in women with PCOS.
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1. Tan S, Hahn S, Benson S, Dietz T, Lahner H, Moeller LC, Schmidt M, Elsenbruch S, Kimmig R, Mann K & Janssen OE. Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance. European Journal of Endocrinology 2007; 157: 669–676.[Abstract/Free Full Text]2. Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI, Sanchón R, San Millán JL & Escobar-Morreale HF. Increased body iron stores of obese women with polycystic ovary syndrome are a consequence of insulin resistance and hyperinsulinism and are not a result of reduced menstrual losses. Diabetes Care 2007; 30: 2309–2313.[Abstract/Free Full Text]3. Swaminathan S, Fonseca VA, Alam MG & Shah SV. The role of iron in diabetes and its complications. Diabetes Care 2007; 30: 1926–1933.[Free Full Text]4. Niederau C, Berger M, Stremmel W, Starke A, Strohmeyer G, Ebert R, Siegel E & Creutzfeldt W. Hyperinsulinaemia in non-cirrhotic haemochromatosis: impaired hepatic insulin degradation? Diabetologia 1984; 26: 441–444.[CrossRef][Web of Science][Medline]5. Merkel PA, Simonson DC, Amiel SA, Plewe G, Sherwin RS, Pearson HA & Tamborlane WV. Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion. New England Journal of Medicine 1988; 318: 809–814.[Abstract]6. Facchini FS & Saylor KL. Effect of iron depletion on cardiovascular risk factors: studies in carbohydrate intolerant patients. Annals of the New York Academy of Sciences 2002; 967: 342–351.[Web of Science][Medline]7. Fernandez-Real JM, Peñarroja G, Castro A, Garcia-Bragado F, Hernandez-Aguado I & Ricart W. Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function. Diabetes 2002; 51: 1000–1004.[Abstract/Free Full Text]
Received 14 November 2007
Accepted 17 November 2007
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