Cyclic fluctuations in human serum lipid and apolipoprotein levels during the normal menstrual cycle: comparison with changes occurring during oral contraceptive therapy

Abstract

The influence of menstrual cycle phases and hormonal contraception on serum lipid and apolipoprotein (apo) levels was investigated in a group of normally menstruating young women. The study period covered a normal menstrual cycle (pretherapy), the fourth cycle of treatment with a triphasic oral contraceptive (OC) preparation, and the cycle immediately following interruption of therapy (cycle 5, posttherapy). Cycle phases were defined on the basis of serum hormone levels and basal body temperature determinations. Significant differences in cholesterol (free and esterified) levels were observed during the menstrual phase of both the normal menstrual cycle (lower) and the OC cycle (higher), when compared with the other phases. Triglycerides, which were higher under OCs, fluctuated similarly throughout the two cycles, but phase differences did not reach statistical significance. Apo AI and apo B were both higher under OCs, and apo B followed a trend similar to cholesterol during the two cycles. During the first month after discontinuation of OCs, cholesterol levels returned progressively to baseline values, while triglycerides were only partially decreased. We conclude that cyclic fluctuations in lipid levels do occur under the influence of both endogenous and exogenous sex hormones.

PIP: Total and free cholesterol, triglycerides, and apolipoproteins apo-A1 and B were determined at precise phases of a pre-therapy menstrual cycle, the 4th cycle on a triphasic oral contraceptive, and in the 1st post-therapy menstrual cycle in 18 women. The triphasic pill contained 5 mcg ethinyl estradiol and 180, 215 and 250 mcg norgestimate for 7 days each (ORF 10131 Triphasic, Ortho Pharmaceuticals, Raritan, NJ). Total cholesterol and triglycerides were measured enzymatically by autoanalyzer (Abbott Bichromatic Analyzer 100), free cholesterol by commercial kit (Boehringer-Mannheim, Mannhein, Germany), and apolipoproteins by electroimmunoassay (Hydragel Apo A1/B, Sebia, Issy- les-Moulineaux, France), with strict quality control using commercial standards. Sera were sampled in 4 phases: Days 3, 4 or 5 of menses, in the follicular phase during rising or peak estradiol levels, at ovulation at peak or highest LH level, and in luteal phase at peak progesterone level. In pill cycles, sera were sampled during each week. Total cholesterol was significantly lower in the menstrual phase, rose on average 9.2% in follicular phase (range -6.8% to +34.4%, in 13 of 18 women), and declined only slightly in luteal phase. Free and esterified cholesterol showed a similar pattern. Triglycerides similarly were lowest in menstrual phase, but were not significantly higher during menstrual cycles. In oral contraceptive cycles, total cholesterol fell an average of 10.7% in the 1st week, and remained at that level until the next pill-free interval or upon discontinuation, when cholesterol rose 11.2%. After discontinuation of the pill, all women resumed normal ovulatory cycles and showed stepwise normalization of cholesterol. Apo-A1 was significantly higher in pill cycles and pill-free intervals than in normal menstrual cycles (p0.001 at all 4 sample points); apo-B was also significantly higher in all samples form pill cycles (p0.05-0.001). There was no correlation between cholesterol levels and any of the hormone levels measured, estradiol, progesterone, LH or FSH.