Effects of menopause, gender and age on lipids and high-density lipoprotein cholesterol subfractions

To distinguish the effects of menopause, gender and age on serum lipid risk markers for vascular disease, including high-density lipoprotein cholesterol (HDL-C) subfractions 2 and 3 (HDL2-C and HDL3-C).

We undertook a cross-sectional database analysis of apparently healthy Caucasian pre- and postmenopausal women and men (n=515, 518 and 800, respectively) not taking drugs affecting lipid metabolism (including contraceptive or post-menopausal steroids). Measurements of serum total cholesterol (TC), low-density lipoprotein (LDL-C), triglycerides (TG), HDL-C, HDL2-C, HDL3-C and non-HDL-C concentrations and the TC/HDL-C concentration ratio were considered.

Men had lower TC than postmenopausal women (p<0.001) and similar LDL-C. Compared with premenopausal women, postmenopausal women had a more atherogenic lipid profile with lower HDL2-C (median 0.67 vs 0.60 mmol/L, p<0.001) but no difference in HDL3-C (0.96 vs 0.96 mmol/L, p=0.8). Compared with either pre or postmenopausal women, men had a more atherogenic profile with lower HDL2-C (0.36 mmol/L) and HDL3-C (0.91 mmol/L, all p<0.001). With standardization for confounding variables, including standardization to age of menopause (50 years), differences apparent in the non-standardized comparisons were generally sustained, although HDL3-C levels were lower at menopause, HDL2-C ceased to differ and LDL-C was lower in postmenopausal women than men.

Male gender is associated with a more atherogenic profile than female gender, with appreciably lower levels of the HDL2-C subfraction. Among women, menopause is associated with a more atherogenic lipid profile, but has less effect than male gender.