Objective To establish whether visceral fat mass is the most significant variable correlating with insulin resistance and other metabolic parameters in women with polycystic ovary syndrome (PCOS).Design Prospective cross-sectional trial.Setting Reproductive medicine clinic.Population Forty women with anovulatory PCOS.Methods Measurements were taken at recruitment, and analysis was performed to define correlations between the outcome measures and the explanatory variables.Main outcome measures Visceral and subcutaneous fat by computed tomography scan, insulin resistance, anthropometric measures, markers of the metabolic syndrome and androgens.Results Strong linear correlation of visceral fat to insulin resistance (r = 0.68, P < 0.001) was observed. There were also statistically significant correlations with fasting insulin (r = 0.73, P < 0.001), homeostasis model assessment b-cell function (r = 0.50, P = 0.007), triglycerides (r = 0.45, P = 0.003), high-density lipoprotein cholesterol (r = -0.42, P = 0.007), urate (r = 0.47, P = 0.002), Sex hormone binding globulin (r = -0.39, P = 0.01) and luteinising hormone (r = -0.32, P = 0.02). There were no significant correlations of testosterone with fat distribution or metabolic parameters. Insulin resistance showed closest correlation to visceral fat mass (r = 0.68, P < 0.001), then to waist circumference (r = 0.62, P < 0.001), with the weakest correlation being waist:hip ratio (r = 0.36, P = 0.01). The best regression model for predicting insulin resistance is with visceral fat mass and triglycerides as the explanatory variables (r = 0.72, P < 0.001).Conclusions Visceral fat is the most significant variable correlating with metabolic dysfunction in women with PCOS. Our data support the hypothesis that visceral fat either causes insulin resistance or is a very early effect of it. It also implies that reducing visceral fat should reduce insulin resistance which may account for the observations that exercise and weight loss appear to be more effective interventions than pharmacological treatments. The best anthropometric measure of insulin resistance is waist circumference.Keywords Fat distribution, insulin resistance, metabolic syndrome, polycystic ovary syndrome, visceral fat.Please cite this paper as: Lord J, Thomas R, Fox B, Acharya U, Wilkin T. The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome.

Objective To establish whether metformin has a significant action in reducing visceral fat and improving other metabolic parameters in women with polycystic ovary syndrome (PCOS).Design Randomised, double-blind, placebo-controlled trial.Setting Reproductive medicine clinic.Population Forty women with anovulatory PCOS.Methods Participants were randomised into receiving metformin 500 mg three times a day or placebo for 3 months.Main outcome measures Fat distribution was measured by computed tomography scan. Secondary outcome measures included serum indices of the metabolic syndrome and evidence of ovulation.Results We found no significant differences in any of the measures of fat distribution between the placebo and metformin groups. The metformin group had significantly lower total cholesterol (P = 0.02), low-density lipoprotein cholesterol (P = 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P = 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy.Conclusions Metformin has no clinically significant effect in reducing visceral fat mass, although it does have a beneficial effect on lipids. This trial lends support to the growing evidence that metformin is not a weight loss drug. Metformin might therefore be used as an adjunct to lifestyle modification in women with PCOS, but not as a substitute for it.Keywords Fat distribution, metabolic syndrome, metformin, polycystic ovary syndrome, visceral fat.Please cite this paper as: Lord J, Thomas R, Fox B, Acharya U, Wilkin T. 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 2006; 113:817-824.

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