Variations in high-density lipoprotein subclasses during the menstrual cycle

Abstract

In a study of 41 healthy premenopausal women, plasma high-density lipoprotein-2a (HDL 2a ) levels (ie, HDL of diameter 8.8 to 9.7 nm) were significantly higher during the luteal phase than during the follicular phase of the cycle. There was no significant variation in HDL 2b or any of the HDL 3 subclasses.Plasma high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I are reported to be higher during the luteal phase than during the follicular phase of the menstrual cycle [1][2][3]. This may be due in part to decreased plasma triglycerides and reduced hepatic lipase activity during the cycle's luteal phase [1,[4][5][6]. These variations in HDL, triglycerides, and hepatic lipase presumably arise in response to hormonal changes. As compared with the follicular phase, the luteal phase is characterized by elevated estrogen, progesterone, and sexhormone-binding protein [6.7]. Estradiol valerate administered orally to postmenopausal women significantly increases HDL 2 cholesterol and significantly decreases hepatic lipase activity [8].Nondenaturing polyacrylamide gradient gel electrophoresis has been used to identify five HDL subclasses: HDL 3c (7.2 to 7.8 nm in diameter), HDL 3b (7.8 to 8.2 nm), HDL 3a , (8.2 to 8.8 nm), HDL 2a (8.8 to 9.7 nm), and HDL 2b (9.7 to 12 nm) [9]. Prior studies have demonstrated that these subclasses show specific relationships to shared environment or inheritance [10] [12,13], and other lipoproteins [14]. Variations in these subclasses during the menstrual cycle have not been previously described. SUBJECTS AND METHODS PatientsThe women were originally sampled as part of a family study of the inheritance of low-density lipoprotein (LDL) subclass phenotypes [15]. The selection of kindreds took place primarily among the Mormon community in the San Francisco Bay Area [15]. The kindreds were not selected for lipid disorders or family history of coronary heart disease, but sequential sampling of kindreds for an LDL-subclass phenotype expression was used [15]. Persons were excluded from this analysis if they reported drinking, smoking, using birth control pills, or taking drugs known to affect plasma HDL. We have previously reported that there were 89 premenopausal women who had regular menstrual periods in this sample [11]. The day of the cycle was NIH Public Access Author ManuscriptMetabolism. Author manuscript; available in PMC 2010 January 25. Published in final edited form as:Metabolism. 1994 November ; 43(11): 1438-1441. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript determined from the following questionnaire item: "Do you have regular cycles or periods? If yes, then indicate starting date of last period." Forty-five women were sampled before we introduced this question into the questionnaire. Three additional women did not answer this question. Thus, the current analyses are based on 41 women. MethodsAll participants provided a single blood sample after an overnight fast. Plasma total cholesterol and triglyceride concentrations were meas...

Polyacrylamide Gradient Gel Electrophoresis of Lipoprotein Subclasses

“…Fortunately, in the research venue, a measure of the subclass concentration that is proportional to the true concentration is generally adequate. Because most statistical tests are location-and scale-invariant (regression analyses, correlations, t tests, analysis of variance, analysis of covariance, and, of course, nonparametric tests), the correct significance levels and correlation coefficients can be obtained, even if the true concentrations of the individual HDL subclasses are unknown, provided a measure of concentration is used that differs from the true concentration through the addition or multiplication of constants [37,[68][69][70][71][72]. A corollary is that the absorbance itself may be used to assess the relationships of the subclass concentrations to other variables and to test for group differences.…”

“…Plasma HDL 2a levels are reported to be lower 14 days, and higher 22 to 32 days, after the beginning of the last menstrual period [71]. Postmenopausal estrogen replacement appears to be associated with increases in HDL 3a and HDL 2a [75].…”

Risk factors for coronary heart disease in two similar Indian population groups, one residing in India, and the other in Sydney, Australia

“…Studies of Indians overseas have included examination of risk factors in immigrant Indians living in such diverse countries as Singapore (Hughes et al, 1998), Britain (Balarajan, 1991), South Africa (Cosnett, 1957) and USA (Anand et al, 1998). Some reports indicate that this excess of risk may not apply uniformly to people from all areas of the subcontinent, for example, the Punjab (Balarajan et al, 1984), however, even people from this region have been shown to have an excess of nonbiochemical risk factors for CHD (Williams et al, 1994). Recent studies of cardiac patients of British and Indian origin (2), and of sons of cardiac patients of Indian and North European origin (Shaukat et al, 1995) confirm these findings, and further attest to the elevation of Lp(a) in South Asians.…”

The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: The stanford coronary risk intervention project baseline survey

“…Five HDL subclasses have so far been identified by this method: HDL 3c (7.2 to 7.8 nm in diameter), HDL 3b (7.8 to 8.2 nm), HDL 3a (8.2 to 8.8 nm), HDL 2a (8.8 to 9.7 nm), and HDL 2b (9.7 to 12 nm) [1]. Prior studies show that different HDL subclasses exhibit specific relationships to exercise [2], weight loss [2], age [3], menstrual status [4], adiposity [3], alcohol intake [3], post-menopausal estrogen replacement [3], other lipoproteins [5,6], and shared genetic and environmental influences within families [7]. Case-control and angiographic studies suggest that coronary heart disease risk may be increased when HDL 2b is decreased relative to HDL 3c and HDL 3b [8][9][10].…”