The Cycle study: a prospective study on cholesterol levels during the menstrual cycle

Abstract Background Previous studies showed fluctuating lipid levels during the menstrual cycle in healthy women with normal cholesterol (nChol). Cycle-related variations in lipid levels in women with familial hypercholesterolemia (FH) have not been studied, while these might have important consequences for lipid management. Purpose To investigate menstrual cycle-related fluctuations in lipid levels in women with FH compared to those with nChol. Methods In the Netherlands and Norway, 20 women with clinical/genetic FH and 63 healthy women with nChol were included - details are presented in the figures. Participants had to have a regular cycle between 21-35 days, while pregnant women, and those using hormone-based contraceptives without hormone free interval (HFI) were excluded. Lipid levels were measured in the follicular (visit 1), ovulation (visit 2), and luteal (visit 3) phases. In women using oral contraceptives (OC) measurements were taken during day 12-14 of the pill period (visit 1) and during day 5-7 of the HFI (visit 2). Results Mean (sd) age of the included subjects was 33 (9) years, BMI 23.9 (4) kg/m2, and cycle duration 28 (2) days. These characteristics were similar in FH and nChol. Women with nChol showed slight, although statistically significant, cycle-related variations in cholesterol levels (mean maximum variation total Chol 0.53, LDL-Chol 0.39 and HDL-Chol 0.22 mmol/L; figure 1). FH women who did not receive statin therapy for various reasons showed largest mean variations (total Chol 0.80, LDL-Chol 0.59 and HDL-Chol 0.23 mmol/L), with the highest lipid levels during the ovulation phase. The women with OC had an increase in total- and LDL-cholesterol (groups combined: mean difference 0.55 and 0.51 mmol/L, respectively) between the two visits (n=9) (figure 2). Conclusions In women with untreated FH and normal cholesterol with a regular menstrual cycle, total- and HDL-cholesterol were highest at ovulation. These menstrual fluctuations were absent in women with FH who used statins. Women with OC showed an increase in total- and LDL-cholesterol from the contraceptive pill period to the HFI. Even though in most women the absolute variation in lipid levels during the menstrual cycle and OC are modest, the moment of measurement can be of clinical value in particular in women with untreated high lipid levels. In these women, it is recommended to measure lipid levels at a fixed time of the menstrual cycle.Figure 1Figure 2