Objective-To determine mechanisms contributing to the altered lipoprotein profile associated with aging and menopause, apolipoprotein B-100 (apoB-100) and apoA-I kinetic behavior was assessed. Methods and Results-Eight premenopausal (25Ϯ3 years) and 16 postmenopausal (65Ϯ6 years) women consumed for 6 weeks a standardized Western diet, at the end of which a primed-constant infusion of deuterated leucine was administered in the fed state to determine the kinetic behavior of triglyceride-rich lipoprotein (TRL), intermediatedensity lipoprotein (IDL), and low-density lipoprotein (LDL) apoB-100, and high-density lipoprotein (HDL) apoA-I. Data were fit to a multicompartmental model using SAAM II to calculate fractional catabolic rate (FCR) and production rate (PR). Total cholesterol, LDL cholesterol (LDL-C), TRL-C, and triglyceride levels were higher (50%, 55%, 130%, and 232%, respectively) in the postmenopausal compared with the premenopausal women, whereas HDL-C levels were similar. Plasma TRL, IDL, and LDL-apoB-100 levels and pool sizes (PS) were significantly higher in the postmenopausal than premenopausal women. These differences were accounted for by lower TRL, IDL, and LDL apoB-100 FCR (PϽ0.05), with no difference in PR. There was no significant difference between groups in HDL-C levels or apoA-I kinetic parameters. Plasma TRL-C concentrations were negatively correlated with TRL apoB-100 FCR (rϭϪ0.46; PϽ0.05) and positively correlated with PR (rϭ0.62; PϽ0.01). Plasma LDL-C concentrations were negatively correlated with LDL apoB-100 FCR (rϭϪ0.70; PϽ0.001) but not PR. Conclusions-The mechanism for the increase in TRL and LDL apoB-100 PS observed in the postmenopausal women was determined predominantly by decreased TRL and LDL catabolism rather than increased production. [3][4][5] Based on data from the Framingham Heart Study, annual rates of first CVD event rise from 7 per 1000 in men 35 to 44 years of age to 68 per 1000 in men 85 to 94 years of age. 6 In women, rates are comparable, but events occur 10 years later. 6 This gender difference in risk has been attributed to a possible protective effect of endogenous female sex hormones. 7 Among women, CVD death rates after menopause are 2 to 3ϫ higher than women the same age before menopause. 6,8 Several studies have also provided compelling evidence that CVD increases after oophorectomy and in women with premature menopause. 9 -11 In the Nurses' Health Study, women who had undergone a bilateral oophorectomy had up to an 8-fold increase in CHD risk. 10 Similarly, in the Women's Health Initiative study, hysterectomized women, with or without ovarian preservation, had a significantly higher 10-year risk of myocardial infarction or coronary death, estimated using the Framingham algorithm compared with nonhysterectomized women. 9 Data from cross-sectional 12-25 and longitudinal studies 12,18,21,26 -29 have shown that menopause alters CVD risk factors. Postmenopausal compared with premenopausal women have higher plasma total cholesterol (TC), low-density lipoprotein ch...