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Article: Dennis Heutling, Hasmik Schulz, Ingrid Nickel, Juergen Kleinstein, Petra Kaltwasser, Sabine Westphal, Friedrich Mittermayer, Michael Wolzt, Katarzyna Krzyzanowska, Harpal Randeva, Guntram Schernthaner, and Hendrik Lehnert Asymmetric Dimethylarginine, Inflammatory and Metabolic Parameters In Women With Polycystic Ovary Syndrome Before and After Metformin Treatment J Clin Endocrinol Metab 2007; 0: jc.2007-0842v1 [Abstract]

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ADMA levels in women with the polycystic ovary syndrome

Dimitrios A Farmakiotis, Christine Charitidou , Ilias Katsikis , and Dimitrios Panidis   (11 February 2008)

ADMA levels in women with the polycystic ovary syndrome 11 February 2008
Dimitrios A Farmakiotis, Medical Doctor Division of Endocrinology and Human Reproduction, Aristotle University of Thessaloniki, Christine Charitidou , Ilias Katsikis , and Dimitrios Panidis Send letter to journal: Re: ADMA levels in women with the polycystic ovary syndrome ergia{at}otenet.gr Dimitrios A Farmakiotis, et al.	We have read with great interest the article by Heutling et al (1), in which asymmetric dimethyl-arginine (ADMA) levels were found significantly higher in women with the polycystic ovary syndrome (PCOS). This finding, as well as the positive correlation between ADMA concentrations and testosterone (T) levels or the free androgen index (FAI) values, are in agreement with our own recently published results (2). In the study by Heutling et al., ADMA levels were significantly decreased after metformin administration, indicating improved endothelial function. Nevertheless, the change in indices of insulin resistance did not reach statistical significance, while T levels and FAI values were significantly improved. The authors mention that the beneficiary effect of metformin might be independent of metabolic parameters, namely insulin resistance. This thesis is in agreement with the results of our own study: ADMA levels were significantly decreased after the administration of natural or synthetic estrogens, combined with anti-androgens, along with a significant decrease in T and FAI, in spite of the fact that insulin resistance was significantly increased (2). Given the above evidence and the fact that increased androgens have been independently associated with endothelial dysfunction (3, 4), we postulate that PCOS-associated endothelial dysfunction might be directly linked to hyperandrogenemia, independent, indeed, of insulin resistance. Further studies, designed to compare the effects of estrogens and antiandrogens, insulin sensitizers and lifestyle measures on endothelial function, in women with PCOS, are definitely needed. References 1. Heutling D, Schulz H, Nickel I, Kleinstein J, Kaltwasser P, Westphal S, Mittermayer F, Wolzt M, Krzyzanowska K, Randeva H, Schernthaner G, Lehnert H 2008 Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment. J Clin Endocrinol Metab 93:82-90 2. Charitidou C, Farmakiotis D, Zournatzi V, Pidonia I, Pegiou T, Karamanis N, Hatzistylianou M, Katsikis I, Panidis D 2008 The administration of estrogens, combined with anti-androgens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels in women with the polycystic ovary syndrome. Atherosclerosis 196:958-965 3. Kravariti M, Naka KK, Kalantaridou SN, Kazakos N, Katsouras CS, Makrigiannakis A, Paraskevaidis EA, Chrousos GP, Tsatsoulis A, Michalis LK 2005 Predictors of endothelial dysfunction in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:5088-5095 4. Dagre A, Lekakis J, Mihas C, Protogerou A, Thalassinou L, Tryfonopoulos D, Douridas G, Papamichael C, Alevizaki M 2006 Association of dehydroepiandrosterone-sulfate with endothelial function in young women with polycystic ovary syndrome. Eur J Endocrinol 154:883-890