Context & Objective

Men typically have a more atherogenic lipid profile than women characterized by higher LDL-cholesterol and triglyceride levels and reduced lipid particle size, contributing to a greater risk for coronary disease. To determine if X-chromosomal gene dosage affects lipid metabolism independent of sex steroid effects, we compared lipid profiles in age- and body mass-matched young women with ovarian failure, differing only in X-chromosome dosage.

Design, setting & patients

Women with premature ovarian failure associated with monosomy X, or Turner syndrome (TS, n = 118) were compared with women with 46,XX premature ovarian failure (POF, n = 51) in an in-patient CRC unit at the NIH. These women were normally on estrogen replacement treatment, but discontinued the estrogen two weeks before study.

Major outcomes

Fasting lipid levels and NMR lipid particle profiles in the two study groups

Results

Average age and body mass were similar in the two groups of women, but LDL-cholesterol (P = 0.001) and triglyceride levels (P = 0.0005) were higher in the TS group. Also among women with TS, average LDL particle size was reduced (P < 0.0001) and LDL particle concentration increased, with a 2-fold increase in the smallest particle categories (P < 0.0001). While total HDL-cholesterol levels were similar, HDL particle size was significantly smaller in women with TS compared with women with POF (P < 0.0001).

Conclusions

45,X women with ovarian failure exhibit a distinctly more atherogenic lipid profile than 46,XX women with ovarian failure, suggesting the second X-chromosome contributes to a more salutary lipid profile in normal women, independent of sex steroid effects.