To the Editor:
We have read with great interest the excellent and well-designed study by Aroda et al. (1). We would like to comment on the potential relationship between serum adiponectin levels, obesity and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS).
Aroda et al. (1), in a population of 31 overweight and obese PCOS women, reported a significant correlation of serum adiponectin levels with all indices of IR. Serum adiponectin levels were significantly reduced in obese PCOS women compared to a population matched for BMI controls (n=6). The authors concluded that IR was the major determinant of serum adiponectin levels.
In a previous study (2), we have noted that serum adiponectin levels in PCOS women with BMI >25 kg/m2 were significantly lower and indices of IR significantly higher (p<0.001) than in PCOS women and controls with BMI <25 kg/m2 (p<0.05).
Moreover, in a subsequent study (3), we have noted a significant decrease in serum adiponectin levels after an oral glucose tolerance test in both normal weight and overweight PCOS women and controls, more pronounced in obese women (p<0.001). These findings are in accordance with those by Aroda et al.; therefore we can assume that obesity and IR play a major role in determining serum adiponectin levels in PCOS women.
The question that arises is whether obesity and IR are the sole determinants of serum adiponectin levels in women with PCOS, or whether chronic oligo/anovulation and hyperandrogenemia might also contribute.
We have recently determined serum adiponectin levels in a cohort of 100 normal weight PCOS women without IR who were classified according to their PCOS phenotype in four equally sized groups matched for age and body mass index (BMI), and 25 matched for age and BMI controls (Panidis D et al, unpublished observations).
Adiponectin levels were significantly higher in the control group, compared to groups with severe PCOS and PCOS with chronic anovulation and hyperandrogenism, but not to groups with ovulatory and mild PCOS (4). Therefore, adiponectin levels were negatively affected by the combination of anovulation and hyperandrogenemia, but not by polycystic ovary morphology.
The differences in circulating adiponectin levels between the main phenotypic groups of normal weight PCOS women without IR seem to reflect the severity of the syndrome, independently of obesity and IR. Therefore, besides the great contribution of obesity and IR, in normal weight PCOS women without IR an additional contribution to the decreased adiponectin serum levels should be attributed to the severity of the syndrome itself.Ilias Katsikis MD, PhD1 Neoklis A. Georgopoulos, MD, PhD2 Tzant Mouslech, MD, PhD1 Anargyros Kourtis, MD, PhD1 Dimitrios Panidis, MD, PhD1 1Division of Endocrinology and Human Reproduction 2nd Department of Obstetrics and Gynecology Aristotle University of Thessaloniki Thessaloniki, Greece 2Department of Obstetrics and Gynecology Division of Reproductive Endocrinology University of Patras Medical School Patra, Greece
1. Aroda V, Ciaraldi TP, Chang SA, Dahan MH, Chang RJ, Henry RR. Circulating and cellular adiponectin in polycystic ovary syndrome: relationship to glucose tolerance and insulin action. Fertil Steril. 2008;89:1200-8.
2. Panidis D, Kourtis A, Farmakiotis D, Mouslech T, Rousso D, Koliakos G. Serum adiponectin levels in women with polycystic ovary syndrome. Hum Reprod. 2003;18:1790-6.
3. Panidis D, Farmakiotis D, Rousso D, Koliakos G, Kaltsas T, Krassas G. Decrease in adiponectin levels in women with polycystic ovary syndrome after an oral glucose tolerance test. Fertil Steril. 2005;83:232-4.
4. Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet 2007;370:685-97.
Published online in Fertility and Sterility DOI: 10.1016/j.fertnstert.2008.12.075
The Authors Reply:
Information in the literature regarding the impact of PCOS on circulating adiponectin levels is mixed. While we (1) and others (2,3) have found adiponectin levels to be most closely associated with BMI and/or measures of insulin resistance, Katsikis et al. report decreased adiponectin levels in normal weight women without insulin resistance, compared to age and BMI-matched controls. We feel that these observations and their attendant conclusions are fully compatible. It may well be that in the presence of obesity and severe insulin resistance (such as with our subjects) it is these factors that are the major determinants of circulating adiponectin levels, overshadowing (but not excluding) the contributions of chronic oligo/anovulation and hyperandrogenemia. However, when obesity and insulin resistance are absent (as in the subjects studied by Katsikis et al), then the severity of the PCOS phenotype becomes more important with regard to adiponectin levels. Variations in circulating adiponectin levels reflect the individual balance of contributions from each of these factors.Theodore P. Ciaraldi, PhD
Department of Medicine
University of California San Diego
VA San Diego Healthcare System San Diego, California
1. Aroda V et al. Fertil Steril 2008;89:1200-8.
2. Sepilian V, Nagamani M. J Soc Gynecol Investig 2005;12:129-34.
3. Spranger J, et al. Clin Endocrinol. 2004;61:738-46.
Published online in Fertility and Sterility DOI: 10.1016/j.fertnstert.2008.12.076