Lipid and Lipoprotein Profile in Menopausal Transition. Effects of Hormones, Age and Fat Distribution

Abstract

The behavior of lipoproteins during the menopausal transition and their relationship with sex hormones and body fat distribution is still unclear. Our aim was to evaluate atherogenic IDL, LDL, Lp(a) and antiatherogenic HDL lipoproteins in four groups of women: premenopausal (n = 20), menopausal transition women with menstrual bleeding (n = 31), menopausal transition women with 3 to 6 months amenorrhea (n = 36), and postmenopausal women (n = 30). We also measured their FSH, LH and estradiol levels along with BMI and waist circumference. Menopausal transition and postmenopausal women showed higher values of waist circumference (p < 0.0032), LDL-cholesterol (p < 0.002), IDL-cholesterol (p < 0.002) and apoprotein B (p < 0.0001) than premenopausal women. Total-cholesterol (p < 0.0001), triglycerides (p < 0.004), IDL-cholesterol and Lp(a) were higher in menopausal transition women with amenorrhea and in postmenopausal women in comparison with premenopausal women. After adjustment according to age and waist circumference, multiple regression analysis showed the increase in total-cholesterol and LDL-cholesterol to be linearly associated to menopausal status and estradiol concentration, whereas Lp(a) was only related to menopausal status. Age was found to be an independent variable in relation to apoprotein B concentration changes. The effect of menopausal status on TG levels did not remain in the model when age, waist and BMI were included (β = 0.05, p = 0.356). HDL-cholesterol levels were the same in all the groups. Menopause, age and the increase in abdominal fat distribution were three independent and significant factors impairing lipoprotein profiles from the beginning of the menopausal transition.

Key words

Lipoproteins - Lp(a) - Estradiol - Perimenopause - Waist circumference

References

• 1 Kannel W, Hjortland M, McNamara P, Gordon T. Menopause and risk of cardiovascular disease: The Framingham study.  Ann Intern Med. 1976;  85 447-452
• 2 Gardner C, Fortmann S, Krauss R. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women.  JAMA. 1996;  276 875-881
• 3 Ma P, Yamamoto T, Goldstein J, Brown M. Increased mRNA for LDL receptor in livers of rabbits treated with 17 alpha-etinil estradiol.  Proc Natl Acad Sci USA. 1986;  83 792-796
• 4 Parini P, Bo A, Rudling M. Importance of estrogen receptors in hepatic LDL receptor regulation.  Arterioscler Thromb Vasc Biol. 1997;  17 1800-1805
• 5 Berg G, Siseles N, Gonzalez A, Contreras Ortiz, Tempone A, Wikinski R. Higher values of hepatic lipase in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins.  Menopause. 2001;  8 51-57
• 6 Li Z, McNamara J R, Fruchart J C, Luc G, Bard J M, Ordovas J M, Wilson P W, Schaefer E J. Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes.  J Lipid Res. 1996;  37 1886-1896
• 7 Matthews K A, Meilahn E, Kuller L H, Kelsey S, Caggiula A, Wing R R. Menopause and risk factors for coronary heart disease.  N Engl J Med. 1989;  321 641-646
• 8 De Aloysio D, Gambacciani M, Meschia M, Pansini F, Modena A, Bolis P, Sassobrio M, Maiocchi G, Peruzzi E. (The Icarus Study Group) . The effect of menopause on blood lipid and lipoprotein levels.  Atherosclerosis. 1999;  147 147-153
• 9 Dahlen G, Guyton J, Attar M, Farner J, Kautz J, Gotto A. Association of levels of lipoprotein (a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography.  Circulation. 1986;  74 758-765
• 10 Sharret A R, Ballantyne C M, Coady S A, Heiss G, Sorlie P E, Catellier D, Patsch W. Corornary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions. The atherosclerosis risk in Communities (ARIC) Study.  Circulation. 2001;  104 1108-1113
• 11 Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H. Lp(a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men.  BMJ. 1990;  301 1248-1251
• 12 Shlipak M, Simon J, Vittinghoff E, Lin F, Barrett-Connor E, Knopp R, Levy R, Hulley S. Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause.  JAMA. 2000;  283 1845-1852
• 13 Kim C, Min Y, Ryu W, Kwak J, Ryoo U. Effect of hormone replacement therapy on Lp(a) and lipid levels in postmenopausal women.  Arch Intern Med. 1996;  156 1693-1700
• 14 Panotopoulos G, Ruiz J, Raison J, Guy-Grand B, Basdevant A. Menopause, fat and lean distribution in obese women.  Maturitas. 1996;  25 11-19
• 15 Gower B, Nagy T, Goran M, Toth M, Poehlman E. Fat distribution and plasma lipid-lipoprotein concentrations in pre and postmenopausal women.  Int J Obes. 1998;  22 605-611
• 16 Björntorp P. Endocrine abnormalities of obesity.  Metabolism. 1995;  44 21-23
• 17 Matthews K, Wing R, Kuller L, Meilahn E, Plantinga P. Influence of the menopause on cardiovascular risk factors and symptoms of middle-aged healthy women.  Arch Intern Med. 1994;  154 2349-2355
• 18 Carr M, Kim K H, Zambon A, Mitchell E, Woods N, Casazza C, Purnell J, Hokanson J, Brunzell J, Schwartz R. Changes in LDL density across the menopausal transition.  J Investig Med. 2000;  48 245-250
• 19 Kanaley J, Sames C, Swick A, Ploutz-Snyder L, Steppan C, Sagendorf K, Feiglin D, Jaynes E, Meyer A, Weinstock S. Abdominal fat distribution in pre-and postmenopausal women: The impact of physical activity, age and menopausal status.  Metabolism. 2001;  50 976-982
• 20 Assman G, Jabs H, Kohnert U, Nolte W, Schriewer H. LDL (low-density-lipoprotein) cholesterol determination in blood serum following precipitation of LDL with poly(vinyl sulphate).  Clin Chim Acta. 1984;  140 77-83
• 21 Warnick G, Benderson J, Albers J. Dextran sulfate-Mg²⁺ precipitation for quantitation of high-density lipoprotein cholesterol.  Clin Chem. 1982;  28 1379-1388
• 22 Wikinski R, Schreier L, Rosental S. New method for isolating and quantifying intermediate and β-very low density lipoprotein cholesterol.  Clin Chem. 1991;  37 1913-1917
• 23 Chang C, Wu C, Yao W, Yang Y, Wu J, Lu F. Relationships of age, menopause and central obesity on cardiovascular disease risk factors in Chinese women.  Int J Obes. 2000;  24 1699-1704
• 24 Berg G, Halperín H, Vilariño A, Tempone A, Wikinski R. Plasmatic Apo-lipoproteins and lipid composition of lipoproteins in pre and postmenopausal women.  Eur Menop J. 1997;  4 4-13
• 25 Hall G, Collins A, Csemiczky G, Landgren B M. Lipoproteins and BMI: a comparison between women during transition to menopause and regularly menstruating healthy women.  Maturitas. 2002;  41 177-185
• 26 Torng P, Su T, Sung F, Chien K, Huang S, Chow S, Lee Y. Effects of menopause on intraindividual changes in serum lipids, blood pressure, and body weight. The Chin-Shan community cardiovascular cohort study.  Atherosclerosis. 2002;  161 409-415
• 27 Couillard C, Bergeron N, PrudŽhomme D, Bergeron J, Tremblay A, Bouchard C, Mauriége P, Després J. Gender difference in postprandial lipemia.  Arterioscler Thromb Vasc Biol. 1999;  19 2448-2455
• 28 Kim C, Kim T, Tyu W S, Ryoo U. Influence of menopause on high density lipoprotein-cholesterol and lipids.  J Korian Med Sci. 2000;  15 380-386
• 29 Vajo Z, Terry J G, Brinton E. Increased intra-abdominal fat may lower HDL levels by increasing the fractional catabolic rate of Lp A-I in postmenopausal women.  Atherosclerosis. 2002;  160 495-501
• 30 Hobbs H, White A. Lp (a): intrigues and insights.  Curr Opin Lipidol. 1999;  10 225-236
• 31 Zysow B, Kauser K, Lawn R, Rubanyi G. Effects of estrus cycle, ovariectomy and treatment with Estrogen, Tamoxifen, and Progesterone on apolipoprotein(a) gen expression in transgenic mice.  Arteriocler Thromb Vasc Biol. 1997;  17 1741-1745
• 32 De Pergola G, Giorgino F, Cospite M, Giagulli V, Cignarelli M, Ferri G, Giorgino R. Relation between sex hormones and serum lipoprotein and lipoprotein (a) concentrations in premenopausal obese women.  Arteriocler Thromb. 1993;  13 675-679
• 33 Carey D, Jenkins A, Campbell L, Freund J, Chisholm D. Abdominal fat and insulin resistance in normal and overweight women: Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM.  Diabetes. 1996;  45 633-638
• 34 Tchernof A, Despres J. Sex steroid hormones, sex hormone-binding globulin and obesity in men and women.  Horm Metab Res. 2000;  32 526-536
• 35 Shelley J, Green A, Smith A, Dudley E, Dennerstein L, Hopper J, Burger H. Relationship of endogenous sex hormones to lipids and blood pressure in mid-aged women.  Ann Epidemiol. 1998;  8 39-45
• 36 Cauley J, Gutai J, Kuller L, Powel J. The relation of endogenous sex steroid hormone concentrations to serum lipid and lipoprotein levels in postmenopausal women.  Am J Epidemiol. 1990;  132 884-894
• 37 Burger H, Dudley E, Robertson D, Dennerstein L. Hormonal changes in the menopause transition.  Recent Prog Horm Res. 2002;  57 257-275