Altered composition of high density lipoproteins in women with the polycystic ovary syndrome.
Women with polycystic ovary syndrome (PCOS) appear at increased cardiovascular risk due in part to a dyslipidemia characterized by increased plasma triglyceride and reduced high density lipoprotein (HDL) cholesterol levels. This is a detailed exploratory study of HDL composition in 35 obese [body mass index (BMI), > 27] and 22 nonobese subjects with PCOS and in 14 healthy obese and 18 nonobese women. Although we found reduced levels of total and HDL2 cholesterol in obese women with PCOS, HDL composition was modified by depletion of lipid relative to protein, with reduced ratios of HDL total cholesterol and HDL phospholipids to apolipoprotein A-I (apoA-I) compared to those in obese controls (P = 0.008 and P = 0.012, respectively). This was explained by reduced cholesterol (P = 0.004) and phospholipid (although not significant, P = 0.07) in HDL with no change in the content of apoA-I, its major protein. Obesity, insulin resistance, and hyperandrogenemia are features of PCOS and potentially affect lipid metabolism. Insulin sensitivity was assessed by the reduction in endogenous glucose concentration after exogenous insulin; the insulin, glucose, and fatty acid responses to oral glucose; and the fasting insulin concentration. When age, BMI, free androgen index, insulin sensitivity determined by all methods, and the presence of PCOS were subjected to stepwise multivariate regression analysis, the presence of PCOS was the most consistent predictor of lipid-depleted HDL (HDL total cholesterol/apoA-I and HDL phospholipids/apoA-I). We speculate that altered activity of hepatic lipase or lipid transfer protein could explain this aspect of the dyslipidemia. Obesity has an important influence on the lipid profile. Obese PCOS and control subjects had higher levels of cholesterol, triglyceride, apoB, and fatty acids than their lean counterparts, and BMI proved the best predictor of blood levels on multiple regression analysis. In contrast, lean PCOS patients had normal sensitivity to insulin and lipid profiles similar to those of the lean controls and did not manifest the HDL abnormalities. Although in PCOS, correlations were obtained between the free androgen index and cholesterol, triglyceride, and apoB levels and between the integrated glucose and insulin responses after oral glucose and fasting fatty acid and triglyceride levels, when age and adiposity were included as covariates only fatty acids and the integrated glucose response remained significantly correlated. Among the controls, total, low density lipoprotein cholesterol, triglycerides, and apoB were related to aspects of insulin sensitivity independent of age and BMI. Lipid metabolism in PCOS is dependent on several related factors, but subjects with PCOS who are obese show a specific reduction in HDL lipid, suggesting a reduced capacity for cholesterol removal from tissues with diminished antiatherogenic potential. Efforts should be directed toward reducing obesity in PCOS to improve the metabolic disturbance in addition to ameliorating the presenting symptoms.
Rajkhowa
M
M
Central Pathology Laboratory, Stoke-on-Trent, Staffordshire, United Kingdom.
Neary
R H
RH
Kumpatla
P
P
Game
F L
FL
Jones
P W
PW
Obhrai
M S
MS
Clayton
R N
RN
D000273:Adipose Tissue / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000473:pathology / Q000503:physiopathology
D000728:Androgens; D012739:Gonadal Steroid Hormones; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL