This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Campos, H. Articles by Sacks, F. M. Search for Related Content PubMed PubMed Citation Articles by Campos, H. Articles by Sacks, F. M.

Effect of Estrogen on Very Low Density Lipoprotein and Low Density Lipoprotein Subclass Metabolism in Postmenopausal Women¹

Department of Nutrition, Harvard School of Public Health (H.C., H.J., F.M.S.); the Department of Obstetrics and Gynecology, Brigham and Women’s Hospital (B.W.W.); and the Channing Laboratory, Department of Medicine, Harvard Medical School (F.M.S.), Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Hannia Campos, Ph.D., Department of Nutrition Room 353A, Building 2, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115. E-mail: hphac{at}gauss.bwh.harvard.edu

Estrogen decreases low density lipoprotein (LDL) particle size, and smaller LDL particles are associated with coronary atherosclerosis. To understand the metabolic basis for this change, we studied the effect of oral 17ß-estradiol (2 mg/day) on apolipoprotein B-100 (apoB) metabolism, in eight healthy postmenopausal women. The study was a randomized, double blinded, placebo-controlled, cross-over trial with intervention sequences of 6 weeks each. ApoB in very low density lipoprotein, intermediate density lipoprotein, and LDL subclasses was endogenously labeled with [D₃]L-leucine, and metabolic rates were calculated by computer modeling. The overall effect of oral estrogen therapy on apoB metabolism was to accelerate the fractional catabolic rates of all particles studied and production rates of all except IDL. For light LDL (density = 1.019–1.036 g/mL), estrogen increased the mean fractional catabolic rate by 63% from 0.59 to 0.96 pools/day (P = 0.02), whereas the production rate increased by a lesser amount (42%) from 575 to 817 mg/day (P = 0.10). These metabolic changes reduced light LDL cholesterol and apoB concentrations by 26% (P = 0.005) and 19% (P = 0.03), respectively. In contrast, dense LDL (density = 1.036–1.063 g/mL) cholesterol and apoB concentrations were unchanged by the intervention, as both the apoB fractional catabolic rate and production rate were significantly increased by similar amounts, 39% (from 0.41 to 0.57 pools/day, P = 0.01) and 38% (from 434 to 601 mg/day; P = 0.003), respectively. Estrogen decreased the predominant LDL peak particle size from 273 to 268 Å (P = 0.04). Thus, estrogen therapy increases the clearance of both light and dense LDL, counteracting increases in production rates. The reduced plasma residence times of light and dense LDL both may be antiatherogenic, even though, for dense LDL, the concentration did not change.

This article has been cited by other articles:

				F. Magkos, B. W. Patterson, B. S. Mohammed, S. Klein, and B. Mittendorfer Women Produce Fewer but Triglyceride-Richer Very Low-Density Lipoproteins than Men J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1311 - 1318. [Abstract] [Full Text] [PDF]

				M. C. G. J. Brouwers, R. M. Cantor, N. Kono, J. l. Yoon, C. J. H. van der Kallen, M. A. L. Bilderbeek-Beckers, M. M. J. van Greevenbroek, A. J. Lusis, and T. W. A. de Bruin Heritability and genetic loci of fatty liver in familial combined hyperlipidemia J. Lipid Res., December 1, 2006; 47(12): 2799 - 2807. [Abstract] [Full Text] [PDF]

				F. Magkos, B. W. Patterson, and B. Mittendorfer No effect of menstrual cycle phase on basal very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1243 - E1249. [Abstract] [Full Text] [PDF]

				C. Zheng, K. Ikewaki, B. W. Walsh, and F. M. Sacks Metabolism of apoB lipoproteins of intestinal and hepatic origin during constant feeding of small amounts of fat J. Lipid Res., August 1, 2006; 47(8): 1771 - 1779. [Abstract] [Full Text] [PDF]

				N. R. Matthan, S. M. Jalbert, S. Lamon-Fava, G. G. Dolnikowski, F. K. Welty, H. R. Barrett, E. J. Schaefer, and A. H. Lichtenstein TRL, IDL, and LDL Apolipoprotein B-100 and HDL Apolipoprotein A-I Kinetics as a Function of Age and Menopausal Status Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1691 - 1696. [Abstract] [Full Text] [PDF]

				H. C. Geiss, S. Bremer, P. H. R. Barrett, C. Otto, and K. G. Parhofer In vivo metabolism of LDL subfractions in patients with heterozygous FH on statin therapy: rebound analysis of LDL subfractions after LDL apheresis J. Lipid Res., August 1, 2004; 45(8): 1459 - 1467. [Abstract] [Full Text] [PDF]

				S. E. Chiuve, L. A. Martin, H. Campos, and F. M. Sacks Effect of the Combination of Methyltestosterone and Esterified Estrogens Compared with Esterified Estrogens Alone on Apolipoprotein CIII and Other Apolipoproteins in Very Low Density, Low Density, and High Density Lipoproteins in Surgically Postmenopausal Women J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2207 - 2213. [Abstract] [Full Text] [PDF]

				F. M. Sacks and H. Campos Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4525 - 4532. [Full Text] [PDF]

				H. Campos, L. A. Moye, S. P. Glasser, M. J. Stampfer, and F. M. Sacks Low-Density Lipoprotein Size, Pravastatin Treatment, and Coronary Events JAMA, September 26, 2001; 286(12): 1468 - 1474. [Abstract] [Full Text] [PDF]

				K. Tomiyasu, B. W. Walsh, K. Ikewaki, H. Judge, and F. M. Sacks Differential Metabolism of Human VLDL According to Content of ApoE and ApoC-III Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1494 - 1500. [Abstract] [Full Text] [PDF]

				H. Campos, D. Perlov, C. Khoo, and F. M. Sacks Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia J. Lipid Res., August 1, 2001; 42(8): 1239 - 1249. [Abstract] [Full Text] [PDF]

				R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [Abstract] [Full Text] [PDF]

				K. Winkler, B. Wetzka, M. M. Hoffmann, I. Friedrich, M. Kinner, M. W. Baumstark, H. Wieland, W. März, and H. P. Zahradnik Low Density Lipoprotein (LDL) Subfractions during Pregnancy: Accumulation of Buoyant LDL with Advancing Gestation J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4543 - 4550. [Abstract] [Full Text]

				A. Karjalainen, J. Heikkinen, M. J. Savolainen, A.-C. Backstrom, and Y. A. Kesaniemi Mechanisms Regulating LDL Metabolism in Subjects on Peroral and Transdermal Estrogen Replacement Therapy Arterioscler. Thromb. Vasc. Biol., April 1, 2000; 20(4): 1101 - 1106. [Abstract] [Full Text] [PDF]

				B. Guerci, H. Antebi, L. Meyer, V. Durlach, O. Ziegler, J.-P. Nicolas, L.-G. Alcindor, and P. Drouin Increased Ability of LDL from Normolipidemic Type 2 Diabetic Women to Generate Peroxides Clin. Chem., September 1, 1999; 45(9): 1439 - 1448. [Abstract] [Full Text] [PDF]

				P. J. Garry, R. N. Baumgartner, S. G. Brodie, G. D. Montoya, H. C. Liang, R. D. Lindeman, and T. M. Williams Estrogen Replacement Therapy, Serum Lipids, and Polymorphism of the Apolipoprotein E Gene Clin. Chem., August 1, 1999; 45(8): 1214 - 1223. [Abstract] [Full Text] [PDF]

				K. A. Greaves, J. S. Parks, J. K. Williams, and J. D. Wagner Intact Dietary Soy Protein, but Not Adding an Isoflavone-Rich Soy Extract to Casein, Improves Plasma Lipids in Ovariectomized Cynomolgus Monkeys J. Nutr., August 1, 1999; 129(8): 1585 - 1592. [Abstract] [Full Text]

				C. Khoo, H. Campos, H. Judge, and F. M. Sacks Effects of estrogenic oral contraceptives on the lipoprotein B particle system defined by apolipoproteins E and C-III content J. Lipid Res., February 1, 1999; 40(2): 202 - 212. [Abstract] [Full Text]

				C. A. Hubel, Y. Shakir, M. J. Gallaher, M. K. McLaughlin, and J. M. Roberts Low-Density Lipoprotein Particle Size Decreases During Normal Pregnancy in Association With Triglyceride Increases Reproductive Sciences, September 1, 1998; 5(5): 244 - 250. [Abstract] [PDF]

				W. Su, H. Campos, H. Judge, B. W. Walsh, and F. M. Sacks Metabolism of Apo(a) and ApoB100 of Lipoprotein(a) in Women: Effect of Postmenopausal Estrogen Replacement J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3267 - 3276. [Abstract] [Full Text]

				R. H. Knopp and X. Zhu Multiple Beneficial Effects of Estrogen on Lipoprotein Metabolism J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 3952 - 3954. [Full Text] [PDF]