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Plasma Lipid and Lipoprotein Levels during the Follicular and Luteal Phases of the Menstrual Cycle

Nutrition/Infection Unit, Department of Family Medicine and Community Health, Tufts University School of Medicine (J.B.B., M.N.W., B.G., S.L.G.), and Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University (J.B.B., M.N.W., S.L.-F., E.J.S., B.G., S.L.G.), Boston, Massachusetts 02111; The Lipid Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging (S.L.-F., E.J.S., J.R.M.), Boston, Massachusetts 02111; Departments of Epidemiology (E.H.) and Biostatistics, Harvard School of Public Health (D.S.), Boston, Massachusetts 02115; and Departments of Medicine and Obstetrics and Gynecology, University of Massachusetts Medical School (C.L.), Worcester, Massachusetts 01605

Address all correspondence and requests for reprints to: Dr. Junaidah B. Barnett, Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Room 245, Jaharis Building, 150 Harrison Avenue, Boston, Massachusetts 02111. E-mail: junaidah.barnett{at}tufts.edu.

Estrogen levels are higher during the luteal compared with the follicular phase of the menstrual cycle. It was hypothesized that the luteal compared with the follicular phase has a lipid and lipoprotein profile associated with decreased coronary heart disease (CHD) risk. This was tested using well-defined data from healthy, well-characterized premenopausal Caucasian women under very controlled metabolic conditions. The percent differences in lipid, lipoprotein, and sex hormone levels between the follicular and luteal phases were estimated using generalized estimating equations after adjusting for age, body mass index, calendar time, and season. The low-density lipoprotein cholesterol (LDL-C) level was 6.2% lower (P = 0.015), and the total cholesterol/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were 5.1% (P = 0.0006) and 8.4% (P = 0.002) lower, respectively, during the luteal phase. Levels of estradiol and other estrogens were significantly higher (by>100% each; P < 0.0001 in all cases) in the luteal phase. These findings support the study hypothesis. Fluctuations in levels of LDL-C and the total cholesterol/HDL-C and LDL-C/HDL-C ratios between menstrual cycle phases need to be considered in the screening and medical monitoring of premenopausal women, especially those with borderline levels. Although small, such fluctuations may prove to be clinically significant in the long run. Studies involving premenopausal women need to more clearly define and validate menstrual cycle phase in the design and interpretation of study results.

This work was supported by NIH Grant R37-CA-45128, Agriculture Research Service Contract 53-3K06-01, and the General Clinical Research Center funded by the Division of Research Resources of the NIH under Grant MO1-RR-00054.

Abbreviations: CHD, Coronary heart disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; VLDL-C, very LDL cholesterol.

¹ C.L. is deceased.

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