Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters

OBJECTIVE Women with polycystic ovary syndrome (PCOS) exhibit an abnormal l ipoprotein profile, characterized by raised concentrations of plasma trigly ceride, marginally elevated low density lipoprotein (LDL)-cholesterol, and reduced high density lipoprotein (HDL)-cholesterol. However, a normal LDL-c holesterol level may be misleading since LDL exists as subpopulations of pa rticles differing In size and atherogenic potential. Smaller LDL particles are more atherogenic and high concentrations often occur in association wit h elevated circulating triglyceride concentrations (but frequently normal t otal LDL-cholesterol), increased hepatic lipase activity (HL) and insulin r esistance. Information on LDL subclasses and HL activity in women with PCOS is sparse. The aim of this study was to determine the concentrations of sm all, dense LDL (LDL-III) in women with PGOS relative to body mass index (BM I)-matched controls. We also examined the association of lipoprotein subfra ction concentrations with endogenous sex hormone concentrations, since exis ting literature suggested that androgens up-regulate and oestrogens down-re gulate HL activity, a key determinant of LDL subfraction distribution. DESI GN Cross sectional study. PATIENTS Fifty-two women with oligomenorrhoea and polycystic ovaries determ ined by ultrasound and BMI matched women with normal menstrual rhythm (NMR) and normal ovarian appearances (n = 14) were recruited from gynaecology cl inics. Anthropometric data and fasting blood samples were obtained for meta bolic, hormonal and LDL subfraction estimation and a heparin provocation te st was used to estimate HL activity. RESULTS SUBJECTS with PCOS demonstrated higher waist:hip ratio (WHR), testo sterone, triglyceride, VLDL-cholesterol concentrations, and HL activity (P< 0.05), whereas SHBG concentrations were significantly lower than controls. PCOS women had higher concentrations (38.0 vs. 25.0 mg/l; P = 0.026) and pr oportions (12.8 vs. 8.2%; P = 0.006) of small, dense LDL (LDL III), relativ e to controls. Within the PCOS group, plasma triglyceride and HL activity w ere the strongest univariate predictors of LDL III mass. They remained as i ndependent predictors in multivariate analysis, and together accounted for 37% of its variability (P = 0.0002). Independent predictors of plasma trigl yceride and HL in turn, were measures of rat distribution (waist circumfere nce or WHR) and fasting insulin concentration. Serum testosterone concentra tion was not associated either in univariate or multivariate analysis with any of the measured lipid, lipoprotein or subfraction parameters nor with H L activity in the women with PCOS. CONCLUSION We conclude that women with polycystic ovary syndrome have incre ased hepatic lipase activity and mass and percentage of small, dense row de nsity lipoprotein relative to body mass index-matched controls with normal menstrual rhythm and normal ovaries. Further, these metabolic perturbances appear related more closely to adiposity/ insulin metabolism than to circul ating androgen levels.