Objective: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. Conclusions: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

Background Younger age at final menstrual period (FMP) is associated with increased risk for cardiovascular disease events. This paper evaluated whether older age at FMP is associated with more favorable patterns of lipid changes during the menopause transition and whether these changes are associated with less subclinical carotid disease in the postmenopausal years. Methods and Results Lipids and lipoproteins were measured repeatedly among 1554 premenopausal women who had a natural menopause during follow‐up years (median=18.8 years); a subset of 890 women also had measures of carotid intima media thickness, adventitial diameter, and plaque. Women who had an older FMP age had less adverse changes in cholesterol from 1 to 3 years after FMP, and in triglycerides from FMP to 3 years after FMP, but they had more adverse changes in ApoB and Apo A1 from 3 years before to 1 year after the FMP. Increasing cholesterol and ApoB from 1 to 3 years after FMP were associated with greater intima media thickness and adventitial diameter, and the greater likelihood of a plaque score >2 the older the age at FMP. Conclusions Despite the epidemiological literature showing early age at FMP is associated with elevated risk for cardiovascular disease events, older age at FMP had inconsistent associations with less adverse lipid changes in midlife, which did not translate into less risk for subclinical carotid disease and in some cases more risk. These findings are restricted to women who experience FMP in the normative age range for the menopausal transition.

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Objective: Longer menstrual cycles have been associated with greater risk of cardiovascular disease, supporting a contribution of abnormal ovarian function. We aimed to characterize trajectories of menstrual cycle length over the menopause transition (MT) and test whether these trajectories are associated with postmenopausal markers of subclinical atherosclerosis.Methods: Women from the Study of Women's Health Across the Nation Daily Hormone Study were included if they had an observed date of the final menstrual period (FMP), recorded cycle lengths from !2 annual menstrual cycles (meanAESD: 4.22 AE 1.91 cycles), and had measurements of postmenopausal carotid intima-media thickness (cIMT) and/or brachial-ankle pulse wave velocity (baPWV). Trajectories of cycle length over the MT were identified using group-based trajectory modeling and linked with cIMT and baPWV using linear regression.Results: We studied 428 women who had 1,808 cycles over the MT (45.1 AE 2.3 y old at baseline visit), and of whom 263 had cIMT, and 213 had baPWV measured postmenopausally (after 13.88 AE 0.42 and 15.25 AE 0.70 y since baseline visit, respectively). Three distinct trajectories of cycle length were identified: stable (no changes in cycle length over the MT among 62.1% of women), late increase (a late increase 2 y before the FMP among 21.8%), and early-increase (an early increase 5 y before the FMP among 16.2%). Women with the late-increase pattern had significantly lower postmenopausal cIMT (0.72 mm) and baPWV (1392 cm/s) levels than the stable group (0.77 mm and 1508 cm/s, respectively) adjusting for race, concurrent age, socioeconomic status, physical activity level, and premenopausal cardiovascular risk profile.Conclusions: Patterns of cycle length over the MT seem to be a marker of future vascular health that may help identify groups at greater or lesser risk of atherosclerosis after menopause.

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