Asymmetric dimethylorginine levels and carotid intima-media thickness in obese patients with polycystic ovary syndrome

Abstract

To the Editor: We would like to thank Dr. Pamuk and colleagues for their fine article (1Pamuk BO, Torun AN, Kulaksizoglu M, Ertugrul D, Ciftci O, Kulaksizoglu S, et al. Asymmetric dimethylarginine levels and carotid intima-media thickness in obese patients with polycystic ovary syndrome and their relationship with metabolic parameters. Fertil Steril. Published online December 22, 2008 [Epub ahead of print].Google Scholar). In that study, they found that there were no significant differences in asymmetric dimethylarginine (ADMA) levels and intima-media thickness (IMT) in a polycystic ovary syndrome (PCOS) group compared with a control group. In addition, there was no relationship between ADMA and IMT in the study. ADMA is an endogenous competitive inhibitor of nitric oxide synthase (NOS) (2Vallance P. Leone A. Calver A. Collier J. Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in renal failure.Lancet. 1992; 339: 572-575Abstract PubMed Scopus (1931) Google Scholar). The enzyme dimethylaminohydrolase (DDAH) hydrolyzes ADMA to L-citruline and methylamine (3Ogawa T. Kimoto M. Sasaoka K. Purification and properties of a new enzyme, NG-dimethylarginine dimethylaminohydrolase, from rat kidney.J Biol Chem. 1989; 264: 10205-10209Abstract Full Text PDF PubMed Google Scholar). It has been proposed that DDAH regulates NOS activity by controlling the concentration of ADMA (4Selley M.L. Homocysteine increases the production of asymmetric dimethylarginine in cultured neurons.J Neurosci Res. 2004; 77: 90-93Crossref PubMed Scopus (37) Google Scholar). There is a close relationship between homocysteine and ADMA, because homocysteine inhibits the activity of DDAH in endothelial cells, causing the accumulation of ADMA and the inhibition of NOS (5Stuhlinger M.C. Tsao P.S. Her J.-H. Kimoto M. Balint R.F. Cooke J.P. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine.Circulation. 2001; 104: 2569-2575Crossref PubMed Scopus (595) Google Scholar). It has also been demonstrated that ADMA levels increase in patients with hyperhomocysteinemia (6Heutling D. Schulz H. Nickel I. Kleinstein J. Kaltwasser P. Westphal S. et al.Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment.J Clin Endocrinol Metab. 2008; 93: 34-36PubMed Google Scholar). In their study, Pamuk et al. found that homocysteine levels were higher in PCOS, but there was no significant difference in ADMA between the groups. The authors reported that they did not find any correlation between ADMA and homocysteine. However, these important findings were stated only in the discussion section. It would be appropriate if they showed these results statistically in the results section. Although it has been reported that there is also a close relationship between ADMA and insulin resistance (6Heutling D. Schulz H. Nickel I. Kleinstein J. Kaltwasser P. Westphal S. et al.Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment.J Clin Endocrinol Metab. 2008; 93: 34-36PubMed Google Scholar), no association was found by Pamuk et al. between insulin resistance and ADMA. The number or percentage of insulin-resistant patients that was assessed by homeostatic model of insulin resistance is important. The results might be different statistically if the percentage of insulin-resistant subjects was higher or lower, and that was not defined in the text. The title of the paper indicates that they studied ADMA and IMT in obese PCOS patients. The definition of obesity was not made in the study. Furthermore, when we look at Table 1 we see that body mass index ranges from 23.9 to 34.4 in the PCOS group and 23.1 to 33.8 in the control group. The title of the manuscript is therefore not suitable, because nonobese patients were also included. Although the aims of the study were to evaluate whether there were any correlations between ADMA, IMT, and metabolic parameters, the authors also investigated the relationship between insulin resistance and some parameters, such as age, body mass index, total cholesterol, free testosterone, and DHEAS, which was not the purpose of the study. Reply of the Authors: Asymmetric dimethylorginine levels and carotid intima-media thickness in obese patients with polycystic ovary syndromeFertility and SterilityVol. 92Issue 1PreviewVerit and Vural have raised several concerns regarding our manuscript which was concerned with asymmetric dimethyl arginine (ADMA) and intima-media thickness (IMT) levels in PCOS. Among their suggestions and concerns was that the body mass index (BMI) issue should be taken into consideration. In the study, we accepted obesity as a BMI >27 kg/m2, as previously adopted by many authors. Unfortunately, there were two subjects in the PCOS group and one in the control group who had normal BMIs. However, this situation could have no significant effect on ADMA or IMT levels, because the mean and the median BMI levels were >27 kg/m2. Full-Text PDF