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Endocrine Research: Thomas M. Barber, Stephen J. Golding, Christopher Alvey, John A. H. Wass, Fredrik Karpe, Stephen Franks, and Mark I. McCarthy Global Adiposity Rather Than Abnormal Regional Fat Distribution Characterizes Women with Polycystic Ovary Syndrome J Clin Endocrinol Metab 2008; 93: 999-1004 [Abstract] [Full text] [PDF]

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Letter to the editor

Evanthia Diamanti-Kandarakis, Charikleia Christakou   (8 April 2008)

Letter to the editor 8 April 2008
Evanthia Diamanti-Kandarakis, MD, PhD Medical School of University of Athens, Athens, Greece, Charikleia Christakou Send letter to journal: Re: Letter to the editor akandara{at}otenet.gr Evanthia Diamanti-Kandarakis, et al.	We read with interest the paper by Barber et al. (1). The authors reported the lack of regional differences in fat distribution between women with PCOS and controls matched for BMI and total fat mass. This finding comes in contrast to data reported by other investigators supporting that visceral adiposity is a characteristic abnormality, independent of obesity, in PCOS (2, 3). The major strength of the present study resides in the use of abdominal MRI, which has significant advantages over other imaging techniques used for fat depot measurements in previous relevant studies. However, a drawback seems to be the heterogeneity of the study population, which included patients with the therapy naive, pure PCOS phenotype, as well as patients studied one week after the suspension of metformin treatment. The authors do not clarify the duration of preceded metformin administration. Neither do they mention the percentage of pretreated subjects within the subgroup of patients who were matched with controls, on which they base their main conclusions, regarding the lack of difference in visceral adiposity between PCOS and controls. Specifically, in the patient group 21 out of 50 subjects were taking metformin, which was stopped one week prior to the MRI scan. This proportion, certainly, does not represent a minority of the PCOS cases, as described by the authors. Of relevant importance is the fact that it is not documented by the literature that one week discontinuation of undetermined duration of preceded metformin treatment (as in the published study), reverts the effects of this medication on metabolic parameters in women with PCOS. In this context, the authors should have discussed available literature showing that metformin treatment can reduce visceral adiposity, determined with CT scan, in women with PCOS (4, 5). Although this is not a consistent effect of metformin treatment (6, 7), a potential improvement of central fat accumulation in pretreated patients could account, to some extent, for the lack of difference between patients and controls in the present study. To exclude this confounder, the authors have conducted a subanalysis restricted to those PCOS cases not pretreated with metformin (n = 29). The authors reported that the results of this subanalysis were compatible with the ones of the whole-group comparison. However, the authors do not describe the characteristics of “therapy-naive” patients, who are not clarified whether they are age and BMI-matched with controls. We would appreciate your consideration, since the present data, if documented, challenge the existing literature regarding pathophysiological aspects of the syndrome and require further clarification by the authors. References 1. Barber TM, Golding SJ, Alvey C, Wass JAS, Karpe F, Franks D, McCarthy MI 2008 Global Adiposity Rather Than Abnormal Regional Fat Distribution Characterizes Women with Polycystic Ovary Syndrome J Clin Endocrinol Metab 93:999-1004 2. Lord J, Thomas R, Fox B, Acharya U, Wilkin T. 2006 The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome. BJOG 113:1203–1209 3. Cascella T, Palomba S, De Sio I, Manguso F, Giallauria F, De Simone B, Tafuri D, Lombardi G, Colao A, Orio F. 2008 Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome. Hum Reprod 23:153-159 4. Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. 1994 Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 43:647-654 5. Pasquali R, Gambineri A, Biscotti D, Vincennati V, Gagliardi L and Colitta D 2000 Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution and androgen and insulin levels in abdominally obese women with and without polycystic ovary syndrome. J Clin Endocrinol Metab 85,2767–2774. 6. Lord JM, Flight IH, Norman RJ. 2003 Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ 327:951-953 7. Lord J, Thomas R, Fox B, Acharya U, Wilkin T. 2006 The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome—a randomised, double-blind, placebo-controlled trial. BJOG 113:817–824